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Sample records for cardiac neural crest

  1. Cardiac neural crest contributes to cardiomyogenesis in zebrafish.

    Science.gov (United States)

    Sato, Mariko; Yost, H Joseph

    2003-05-01

    In birds and mammals, cardiac neural crest is essential for heart development and contributes to conotruncal cushion formation and outflow tract septation. The zebrafish prototypical heart lacks outflow tract septation, raising the question of whether cardiac neural crest exists in zebrafish. Here, results from three distinct lineage-labeling approaches identify zebrafish cardiac neural crest cells and indicate that these cells have the ability to generate MF20-positive muscle cells in the myocardium of the major chambers during development. Fate-mapping demonstrates that cardiac neural crest cells originate both from neural tube regions analogous to those found in birds, as well as from a novel region rostral to the otic vesicle. In contrast to other vertebrates, cardiac neural crest invades the myocardium in all segments of the heart, including outflow tract, atrium, atrioventricular junction, and ventricle in zebrafish. Three distinct groups of premigratory neural crest along the rostrocaudal axis have different propensities to contribute to different segments in the heart and are correspondingly marked by unique combinations of gene expression patterns. Zebrafish will serve as a model for understanding interactions between cardiac neural crest and cardiovascular development.

  2. The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish.

    Science.gov (United States)

    Nguyen, Catherine T; Langenbacher, Adam; Hsieh, Michael; Chen, Jau-Nian

    2010-05-01

    Leo1 is a component of the Polymerase-Associated Factor 1 (PAF1) complex, an evolutionarily conserved protein complex involved in gene transcription regulation and chromatin remodeling. The role of leo1 in vertebrate embryogenesis has not previously been examined. Here, we report that zebrafish leo1 encodes a nuclear protein that has a similar molecular structure to Leo1 proteins from other species. From a genetic screen, we identified a zebrafish mutant defective in the leo1 gene. The truncated Leo1(LA1186) protein lacks a nuclear localization signal and is distributed mostly in the cytoplasm. Phenotypic analysis showed that while the initial patterning of the primitive heart tube is not affected in leo1(LA1186) mutant embryos, the differentiation of cardiomyocytes at the atrioventricular boundary is aberrant, suggesting a requirement for Leo1 in cardiac differentiation. In addition, the expression levels of markers for neural crest-derived cells such as crestin, gch2, dct and mitfa are greatly reduced in leo1(LA1186) mutants, indicating a requirement for Leo1 in maintaining the neural crest population. Consistent with this finding, melanocyte and xanthophore populations are severely reduced, craniofacial cartilage is barely detectable, and mbp-positive glial cells are absent in leo1(LA1186) mutants after three days of development. Taken together, these results provide the first genetic evidence of the requirement for Leo1 in the development of the heart and neural crest cell populations.

  3. 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.

  4. Neural crest migration: trailblazing ahead

    OpenAIRE

    Kulesa, Paul M.; McLennan, Rebecca

    2015-01-01

    Embryonic cell migration patterns are amazingly complex in the timing and spatial distribution of cells throughout the vertebrate landscape. However, advances in in vivo visualization, cell interrogation, and computational modeling are extracting critical features that underlie the mechanistic nature of these patterns. The focus of this review highlights recent advances in the study of the highly invasive neural crest cells and their migratory patterns during embryonic development. We discuss...

  5. The neural crest and neural crest cells: discovery and significance for theories of embryonic organization

    Indian Academy of Sciences (India)

    Brian K Hall

    2008-12-01

    The neural crest has long fascinated developmental biologists, and, increasingly over the past decades, evolutionary and evolutionary developmental biologists. The neural crest is the name given to the fold of ectoderm at the junction between neural and epidermal ectoderm in neurula-stage vertebrate embryos. In this sense, the neural crest is a morphological term akin to head fold or limb bud. This region of the dorsal neural tube consists of neural crest cells, a special population(s) of cell, that give rise to an astonishing number of cell types and to an equally astonishing number of tissues and organs. Neural crest cell contributions may be direct — providing cells — or indirect — providing a necessary, often inductive, environment in which other cells develop. The enormous range of cell types produced provides an important source of evidence of the neural crest as a germ layer, bringing the number of germ layers to four — ectoderm, endoderm, mesoderm, and neural crest. 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 secondary neurulation, and present evidence of the neural crest as the fourth germ layer. A companion paper (Hall, Evol. Biol. 2008) deals with the evolutionary origins of the neural crest and neural crest cells.

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

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    Bridget T Jacques-Fricke

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

  7. FGF signaling transforms non-neural ectoderm into neural crest.

    Science.gov (United States)

    Yardley, Nathan; García-Castro, Martín I

    2012-12-15

    The neural crest arises at the border between the neural plate and the adjacent non-neural ectoderm. It has been suggested that both neural and non-neural ectoderm can contribute to the neural crest. Several studies have examined the molecular mechanisms that regulate neural crest induction in neuralized tissues or the neural plate border. Here, using the chick as a model system, we address the molecular mechanisms by which non-neural ectoderm generates neural crest. We report that in response to FGF the non-neural ectoderm can ectopically express several early neural crest markers (Pax7, Msx1, Dlx5, Sox9, FoxD3, Snail2, and Sox10). Importantly this response to FGF signaling can occur without inducing ectopic mesodermal tissues. Furthermore, the non-neural ectoderm responds to FGF by expressing the prospective neural marker Sox3, but it does not express definitive markers of neural or anterior neural (Sox2 and Otx2) tissues. These results suggest that the non-neural ectoderm can launch the neural crest program in the absence of mesoderm, without acquiring definitive neural character. Finally, we report that prior to the upregulation of these neural crest markers, the non-neural ectoderm upregulates both BMP and Wnt molecules in response to FGF. Our results provide the first effort to understand the molecular events leading to neural crest development via the non-neural ectoderm in amniotes and present a distinct response to FGF signaling. PMID:23000357

  8. Effect of dihydrofolate reductase gene knock-down on the expression of heart and neural crest derivatives expressed transcript 2 in zebrafish cardiac development

    Institute of Scientific and Technical Information of China (English)

    SUN Shu-na; GUI Yong-hao; WANG Yue-xiang; QIAN Lin-xi; JIANG Qiu; LIU Dong; SONG Hou-yan

    2007-01-01

    Background Folic acid is very important for embryonic development and dihydrofolate reductase is one of the key enzymes in the process of folic acid performing its biological function. Therefore, the dysfunction of dihydrofolate reductase can inhibit the function of folic acid and finally cause the developmental malformations. In this study, we observed the abnormal cardiac phenotypes in dihydrofolate reductase (DHFR) gene knock-down zebrafish embryos,investigated the effect of DHFR on the expression of heart and neural crest derivatives expressed transcript 2 (HAND2)and explored the possible mechanism of DHFR knock-down inducing zebrafish cardiac malformations.Methods Morpholino oligonucleotides were microinjected into fertilized eggs to knock down the functions of DHFR or HAND2. Full length of HAND2 mRNA which was transcribed in vitro was microinjected into fertilized eggs to overexpress HAND2. The cardiac morphologies, the heart rates and the ventricular shortening fraction were observed and recorded under the microscope at 48 hours post fertilization. Whole-mount in situ hybridization and real-time PCR were performed to detect HAND2 expression.Results DHFR or HAND2 knock-down caused the cardiac malformation in zebrafish. The expression of HAND2 was obviously reduced in DHFR knock-down embryos (P<0.05). Microinjecting HAND2 mRNA into fertilized eggs can induce HAND2 overexpression. HAND2 overexpression rescued the cardiac malformation phenotypes of DHFR knock-down embryos.Conclusions DHFR plays a crucial role in cardiac development. The down-regulation of HAND2 caused by DHFR knock-down is the possible mechanism of DHFR knock-down inducing the cardiac malformation.

  9. Neural crest contributions to the lamprey head

    Science.gov (United States)

    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

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

  10. Two developmentally distinct populations of neural crest cells contribute to the zebrafish heart.

    Science.gov (United States)

    Cavanaugh, Ann M; Huang, Jie; Chen, Jau-Nian

    2015-08-15

    Cardiac neural crest cells are essential for outflow tract remodeling in animals with divided systemic and pulmonary circulatory systems, but their contributions to cardiac development in animals with a single-loop circulatory system are less clear. Here we genetically labeled neural crest cells and examined their contribution to the developing zebrafish heart. We identified two populations of neural crest cells that contribute to distinct compartments of zebrafish cardiovascular system at different developmental stages. A stream of neural crest cells migrating through pharyngeal arches 1 and 2 integrates into the myocardium of the primitive heart tube between 24 and 30 h post fertilization and gives rise to cardiomyocytes. A second wave of neural crest cells migrating along aortic arch 6 envelops the endothelium of the ventral aorta and invades the bulbus arteriosus after three days of development. Interestingly, while inhibition of FGF signaling has no effect on the integration of neural crest cells to the primitive heart tube, it prevents these cells from contributing to the outflow tract, demonstrating disparate responses of neural crest cells to FGF signaling. Furthermore, neural crest ablation in zebrafish leads to multiple cardiac defects, including reduced heart rate, defective myocardial maturation and a failure to recruit progenitor cells from the second heart field. These findings add to our understanding of the contribution of neural crest cells to the developing heart and provide insights into the requirement for these cells in cardiac maturation.

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

    International Nuclear Information System (INIS)

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

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

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    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.

  13. Migrating into Genomics with the Neural Crest

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    Marianne E. Bronner

    2014-01-01

    Full Text Available Neural crest cells are a fascinating embryonic cell type, unique to vertebrates, which arise within the central nervous system but emigrate soon after its formation and migrate to numerous and sometimes distant locations in the periphery. Following their migratory phase, they differentiate into diverse derivatives ranging from peripheral neurons and glia to skin melanocytes and craniofacial cartilage and bone. The molecular underpinnings underlying initial induction of prospective neural crest cells at the neural plate border to their migration and differentiation have been modeled in the form of a putative gene regulatory network. This review describes experiments performed in my laboratory in the past few years aimed to test and elaborate this gene regulatory network from both an embryonic and evolutionary perspective. The rapid advances in genomic technology in the last decade have greatly expanded our knowledge of important transcriptional inputs and epigenetic influences on neural crest development. The results reveal new players and new connections in the neural crest gene regulatory network and suggest that it has an ancient origin at the base of the vertebrate tree.

  14. Neural crest: The fourth germ layer

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    K Shyamala

    2015-01-01

    Full Text Available The neural crest cells (NCCs, a transient group of cells that emerges from the dorsal aspect of the neural tube during early vertebrate development has been a fascinating group of cells because of its multipotency, long range migration through embryo and its capacity to generate a prodigious number of differentiated cell types. For these reasons, although derived from the ectoderm, the neural crest (NC has been called the fourth germ layer. The non neural ectoderm, the neural plate and the underlying mesoderm are needed for the induction and formation of NC cells. Once formed, NC cells start migrating as a wave of cells, moving away from the neuroepithelium and quickly splitting into distinct streams. These migrating NCCs home in to different regions and give rise to plethora of tissues. Umpteen number of signaling molecules are essential for formation, epithelial mesenchymal transition, delamination, migration and localization of NCC. Authors believe that a clear understanding of steps and signals involved in NC formation, migration, etc., may help in understanding the pathogenesis behind cancer metastasis and many other diseases. Hence, we have taken this review to discuss the various aspects of the NC cells.

  15. The origin and evolution of the neural crest

    OpenAIRE

    Donoghue, Philip C. J.; Graham, Anthony; Kelsh, Robert N.

    2008-01-01

    Many of the features that distinguish the vertebrates from other chordates are derived from the neural crest, and it has long been argued that the emergence of this multipotent embryonic population was a key innovation underpinning vertebrate evolution. More recently, however, a number of studies have suggested that the evolution of the neural crest was less sudden than previously believed. This has exposed the fact that neural crest, as evidenced by its repertoire of derivative cell types, h...

  16. Endothelial cells regulate neural crest and second heart field morphogenesis

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    Michal Milgrom-Hoffman

    2014-07-01

    Full Text Available Cardiac and craniofacial developmental programs are intricately linked during early embryogenesis, which is also reflected by a high frequency of birth defects affecting both regions. The molecular nature of the crosstalk between mesoderm and neural crest progenitors and the involvement of endothelial cells within the cardio–craniofacial field are largely unclear. Here we show in the mouse that genetic ablation of vascular endothelial growth factor receptor 2 (Flk1 in the mesoderm results in early embryonic lethality, severe deformation of the cardio–craniofacial field, lack of endothelial cells and a poorly formed vascular system. We provide evidence that endothelial cells are required for migration and survival of cranial neural crest cells and consequently for the deployment of second heart field progenitors into the cardiac outflow tract. Insights into the molecular mechanisms reveal marked reduction in Transforming growth factor beta 1 (Tgfb1 along with changes in the extracellular matrix (ECM composition. Our collective findings in both mouse and avian models suggest that endothelial cells coordinate cardio–craniofacial morphogenesis, in part via a conserved signaling circuit regulating ECM remodeling by Tgfb1.

  17. Current perspectives of the signaling pathways directing neural crest induction

    OpenAIRE

    Stuhlmiller, Timothy J.; García-Castro, Martín I.

    2012-01-01

    The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the ...

  18. Negative chemotaxis does not control quail neural crest cell dispersion.

    Science.gov (United States)

    Erickson, C A; Olivier, K R

    1983-04-01

    Negative chemotaxis has been proposed to direct dispersion of amphibian neural crest cells away from the neural tube (V. C. Twitty, 1949, Growth 13(Suppl. 9), 133-161). We have reexamined this hypothesis using quail neural crest and do not find evidence for it. When pigmented or freshly isolated neural crest cells are covered by glass shards to prevent diffusion of a "putative" chemotactic agent away from the cells and into the medium, we find a decrease in density of cells beneath the coverslip as did Twitty and Niu (1948, J. Exp. Zool. 108, 405-437). Unlike those investigators, however, we find the covered cells move slower than uncovered cells and that the decrease in density can be attributed to cessation of cell division and increased cell death in older cultures, rather than directed migration away from each other. In cell systems where negative chemotaxis has been demonstrated, a "no man's land" forms between two confronted explants (Oldfield, 1963, Exp. Cell Res. 30, 125-138). No such cell-free space forms between confronted neural crest explants, even if the explants are closely covered to prevent diffusion of the negative chemotactic material. If crest cell aggregates are drawn into capillary tubes to allow accumulation of the putative material, the cells disperse farther, the wider the capillary tube bore. This is contrary to what would be expected if dispersion depended on accumulation of this material. Also, no difference in dispersion is noted between cells in the center of the tubes versus cells near the mouth of the tubes where the tube medium is freely exchanging with external fresh medium. Alternative hypotheses for directionality of crest migration in vivo are discussed. PMID:6832483

  19. Current perspectives of the signaling pathways directing neural crest induction.

    Science.gov (United States)

    Stuhlmiller, Timothy J; García-Castro, Martín I

    2012-11-01

    The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse. PMID:22547091

  20. Current perspectives of the signaling pathways directing neural crest induction.

    Science.gov (United States)

    Stuhlmiller, Timothy J; García-Castro, Martín I

    2012-11-01

    The neural crest is a migratory population of embryonic cells with a tremendous potential to differentiate and contribute to nearly every organ system in the adult body. Over the past two decades, an incredible amount of research has given us a reasonable understanding of how these cells are generated. Neural crest induction involves the combinatorial input of multiple signaling pathways and transcription factors, and is thought to occur in two phases from gastrulation to neurulation. In the first phase, FGF and Wnt signaling induce NC progenitors at the border of the neural plate, activating the expression of members of the Msx, Pax, and Zic families, among others. In the second phase, BMP, Wnt, and Notch signaling maintain these progenitors and bring about the expression of definitive NC markers including Snail2, FoxD3, and Sox9/10. In recent years, additional signaling molecules and modulators of these pathways have been uncovered, creating an increasingly complex regulatory network. In this work, we provide a comprehensive review of the major signaling pathways that participate in neural crest induction, with a focus on recent developments and current perspectives. We provide a simplified model of early neural crest development and stress similarities and differences between four major model organisms: Xenopus, chick, zebrafish, and mouse.

  1. Progenitors of the protochordate ocellus as an evolutionary origin of the neural crest

    OpenAIRE

    Ivashkin, Evgeniy; Adameyko, Igor

    2013-01-01

    The neural crest represents a highly multipotent population of embryonic stem cells found only in vertebrate embryos. Acquisition of the neural crest during the evolution of vertebrates was a great advantage, providing Chordata animals with the first cellular cartilage, bone, dentition, advanced nervous system and other innovations. Today not much is known about the evolutionary origin of neural crest cells. Here we propose a novel scenario in which the neural crest originates from neuroectod...

  2. 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.

  3. Neural crest induction by paraxial mesoderm in Xenopus embryos requires FGF signals.

    Science.gov (United States)

    Monsoro-Burq, Anne-Hélène; Fletcher, Russell B; Harland, Richard M

    2003-07-01

    At the border of the neural plate, the induction of the neural crest can be achieved by interactions with the epidermis, or with the underlying mesoderm. Wnt signals are required for the inducing activity of the epidermis in chick and amphibian embryos. Here, we analyze the molecular mechanisms of neural crest induction by the mesoderm in Xenopus embryos. Using a recombination assay, we show that prospective paraxial mesoderm induces a panel of neural crest markers (Slug, FoxD3, Zic5 and Sox9), whereas the future axial mesoderm only induces a subset of these genes. This induction is blocked by a dominant negative (dn) form of FGFR1. However, neither dnFGFR4a nor inhibition of Wnt signaling prevents neural crest induction in this system. Among the FGFs, FGF8 is strongly expressed by the paraxial mesoderm. FGF8 is sufficient to induce the neural crest markers FoxD3, Sox9 and Zic5 transiently in the animal cap assay. In vivo, FGF8 injections also expand the Slug expression domain. This suggests that FGF8 can initiate neural crest formation and cooperates with other DLMZ-derived factors to maintain and complete neural crest induction. In contrast to Wnts, eFGF or bFGF, FGF8 elicits neural crest induction in the absence of mesoderm induction and without a requirement for BMP antagonists. In vivo, it is difficult to dissociate the roles of FGF and WNT factors in mesoderm induction and neural patterning. We show that, in most cases, effects on neural crest formation were parallel to altered mesoderm or neural development. However, neural and neural crest patterning can be dissociated experimentally using different dominant-negative manipulations: while Nfz8 blocks both posterior neural plate formation and neural crest formation, dnFGFR4a blocks neural patterning without blocking neural crest formation. These results suggest that different signal transduction mechanisms may be used in neural crest induction, and anteroposterior neural patterning. PMID:12783784

  4. Distinct enhancers at the Pax3 locus can function redundantly to regulate neural tube and neural crest expressions.

    Science.gov (United States)

    Degenhardt, Karl R; Milewski, Rita C; Padmanabhan, Arun; Miller, Mayumi; Singh, Manvendra K; Lang, Deborah; Engleka, Kurt A; Wu, Meilin; Li, Jun; Zhou, Diane; Antonucci, Nicole; Li, Li; Epstein, Jonathan A

    2010-03-15

    Pax3 is a transcription factor expressed in somitic mesoderm, dorsal neural tube and pre-migratory neural crest during embryonic development. We have previously identified cis-acting enhancer elements within the proximal upstream genomic region of Pax3 that are sufficient to direct functional expression of Pax3 in neural crest. These elements direct expression of a reporter gene to pre-migratory neural crest in transgenic mice, and transgenic expression of a Pax3 cDNA using these elements is sufficient to rescue neural crest development in mice otherwise lacking endogenous Pax3. We show here that deletion of these enhancer sequences by homologous recombination is insufficient to abrogate neural crest expression of Pax3 and results in viable mice. We identify a distinct enhancer in the fourth intron that is also capable of mediating neural crest expression in transgenic mice and zebrafish. Our analysis suggests the existence of functionally redundant neural crest enhancer modules for Pax3.

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

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    Slack Jonathan MW

    2007-05-01

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

  6. New genes in the evolution of the neural crest differentiation program

    OpenAIRE

    Martínez-Morales, Juan Ramón; Henrich, Thorsten; Ramialison, Mirana; Wittbrodt, Joachim

    2007-01-01

    BACKGROUND: Development of the vertebrate head depends on the multipotency and migratory behavior of neural crest derivatives. This cell population is considered a vertebrate innovation and, accordingly, chordate ancestors lacked neural crest counterparts. The identification of neural crest specification genes expressed in the neural plate of basal chordates, in addition to the discovery of pigmented migratory cells in ascidians, has challenged this hypothesis. These new findings revive th...

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

    OpenAIRE

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

    2003-01-01

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

  8. File list: DNS.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.20.AllAg.hESC_derived_neural_crests hg19 DNase-seq Pluripotent stem cell hESC derived neural crest...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

  9. File list: DNS.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.10.AllAg.hESC_derived_neural_crests hg19 DNase-seq Pluripotent stem cell hESC derived neural crest...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.PSC.10.AllAg.hESC_derived_neural_crests.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.05.AllAg.hESC_derived_neural_crests hg19 DNase-seq Pluripotent stem cell hESC derived neural crest...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

  11. File list: DNS.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.PSC.50.AllAg.hESC_derived_neural_crests hg19 DNase-seq Pluripotent stem cell hESC derived neural crest...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.PSC.50.AllAg.hESC_derived_neural_crests.bed ...

  12. Thyroid hormone and retinoic acid interact to regulate zebrafish craniofacial neural crest development.

    Science.gov (United States)

    Bohnsack, Brenda L; Kahana, Alon

    2013-01-15

    Craniofacial and ocular morphogenesis require proper regulation of cranial neural crest migration, proliferation, survival and differentiation. Although alterations in maternal thyroid hormone (TH) are associated with congenital craniofacial anomalies, the role of TH on the neural crest has not been previously described. Using zebrafish, we demonstrate that pharmacologic and genetic alterations in TH signaling disrupt cranial neural crest migration, proliferation, and survival, leading to craniofacial, extraocular muscle, and ocular developmental abnormalities. In the rostral cranial neural crest that gives rise to the periocular mesenchyme and the frontonasal process, retinoic acid (RA) rescued migratory defects induced by decreased TH signaling. In the caudal cranial neural crest, TH and RA had reciprocal effects on anterior and posterior pharyngeal arch development. The interactions between TH and RA signaling were partially mediated by the retinoid X receptor. We conclude that TH regulates both rostral and caudal cranial neural crest. Further, coordinated interactions of TH and RA are required for proper craniofacial and ocular development.

  13. Neural crest and placode contributions to olfactory development.

    Science.gov (United States)

    Suzuki, Jun; Osumi, Noriko

    2015-01-01

    Olfaction is the sense of smell that influences many primitive behaviors for survival, e.g., feeding, reproduction, social interaction, and fear response. The olfactory system is an evolutionarily ancient sensory system and composed of the olfactory epithelium (OE), the olfactory bulb (OB), and the olfactory cortex. The OE gives rise to olfactory receptor neurons (ORNs), i.e., primary sensory receptor cells whose axons project directly to the OB. The ORNs are unique in the way that they are continuously replaced during physiological turnover or following injury throughout life. In the OE, horizontal basal cells, i.e., flat and quiescent cells attached to the basal lamina, are now thought to be tissue stem cells. Although OE cells, especially ORNs, were hypothesized to be derived from the olfactory placode (OP), recent genetic fate-mapping studies using Cre reporter mice indicate a dual origin, i.e., the OP and neural crest (NC), of the olfactory system. The NC is a transient embryonic tissue that is formed between the dorsal neuroepithelium and epidermis. Neural crest cells (NCCs) are multipotent cells that migrate into various target tissues and differentiate into various cell types, including neurons and glia of the peripheral nervous system, cranial cartilage and bone, and melanocytes. Recent studies have revealed that neural crest-derived cells (NCDCs) are widely distributed in adult tissues, and that a subset of NCDCs still possesses NCC-like multipotency. Here, we review classical and recent studies of the olfactory system, especially focusing on the contribution of the NC and OP to the OE development. PMID:25662265

  14. Zebrafish arl6ip1 is required for neural crest development during embryogenesis.

    Directory of Open Access Journals (Sweden)

    Chi-Tang Tu

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

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

    OpenAIRE

    Arnold, Thomas D.; Keling Zang; Ainara Vallejo-Illarramendi

    2013-01-01

    SUMMARY 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 rol...

  16. Neural Crest As the Source of Adult Stem Cells

    Science.gov (United States)

    Pierret, Chris; Spears, Kathleen; Maruniak, Joel A.; Kirk, Mark D.

    2012-01-01

    Recent studies suggest that adult stem cells can cross germ layer boundaries. For example, bone marrow-derived stem cells appear to differentiate into neurons and glial cells, as well as other types of cells. How can stem cells from bone marrow, pancreas, skin, or fat become neurons and glia; in other words, what molecular and cellular events direct mesodermal cells to a neural fate? Transdifferentiation, dediffereniation, and fusion of donor adult stem cells with fully differentiated host cells have been proposed to explain the plasticity of adult stem cells. Here we review the origin of select adult stem cell populations and propose a unifying hypothesis to explain adult stem cell plasticity. In addition, we outline specific experiments to test our hypothesis. We propose that peripheral, tissue-derived, or adult stem cells are all progeny of the neural crest. PMID:16646675

  17. 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.

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

    Science.gov (United States)

    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

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

  19. Identification and dissection of a key enhancer mediating cranial neural crest specific expression of transcription factor, Ets-1

    OpenAIRE

    Barembaum, Meyer; Bronner, Marianne E.

    2013-01-01

    Neural crest cells form diverse derivatives that vary according to their level of origin along the body axis, with only cranial neural crest cells contributing to facial skeleton. Interestingly, the transcription factor Ets-1 is uniquely expressed in cranial but not trunk neural crest, where it functions as a direct input into neural crest specifier genes, Sox10 and FoxD3. We have isolated and interrogated a cis-regulatory element, conserved between birds and mammals, that drives reporter exp...

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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  2. File list: NoD.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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

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

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  7. File list: His.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

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

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  9. File list: His.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

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

    Lifescience Database Archive (English)

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  11. File list: NoD.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Pol.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: NoD.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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  16. File list: NoD.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Pol.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. Neural crest stem cells: discovery, properties and potential for therapy

    Institute of Scientific and Technical Information of China (English)

    Annita Achilleos; Paul A Trainor

    2012-01-01

    Neural crest (NC) cells are a migratory cell population synonymous with vertebrate evolution.They generate a wide variety of cell and tissue types during embryonic and adult development including cartilage and bone,connective tissue,pigment and endocrine cells as well as neurons and glia amongst many others.Such incredible lineage potential combined with a limited capacity for self-renewal,which persists even into adult life,demonstrates that NC cells bear the key hallmarks of stem and progenitor cells.In this review,we describe the identification,characterization and isolation of NC stem and progenitor cells from different tissues in both embryo and adult organisms.We discuss their specific properties and their potential application in cell-based tissue and disease-specific repair.

  19. 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.

  20. A novel role for Lh3 dependent ECM modifications during neural crest cell migration in zebrafish.

    Directory of Open Access Journals (Sweden)

    Santanu Banerjee

    Full Text Available During vertebrate development, trunk neural crest cells delaminate along the entire length of the dorsal neural tube and initially migrate as a non-segmented sheet. As they enter the somites, neural crest cells rearrange into spatially restricted segmental streams. Extracellular matrix components are likely to play critical roles in this transition from a sheet-like to a stream-like mode of migration, yet the extracellular matrix components and their modifying enzymes critical for this transition are largely unknown. Here, we identified the glycosyltransferase Lh3, known to modify extracellular matrix components, and its presumptive substrate Collagen18A1, to provide extrinsic signals critical for neural crest cells to transition from a sheet-like migration behavior to migrating as a segmental stream. Using live cell imaging we show that in lh3 null mutants, neural crest cells fail to transition from a sheet to a stream, and that they consequently enter the somites as multiple streams, or stall shortly after entering the somites. Moreover, we demonstrate that transgenic expression of lh3 in a small subset of somitic cells adjacent to where neural crest cells switch from sheet to stream migration restores segmental neural crest cell migration. Finally, we show that knockdown of the presumptive Lh3 substrate Collagen18A1 recapitulates the neural crest cell migration defects observed in lh3 mutants, consistent with the notion that Lh3 exerts its effect on neural crest cell migration by regulating post-translational modifications of Collagen18A1. Together these data suggest that Lh3-Collagen18A1 dependent ECM modifications regulate the transition of trunk neural crest cells from a non-segmental sheet like migration mode to a segmental stream migration mode.

  1. A novel role for Lh3 dependent ECM modifications during neural crest cell migration in zebrafish.

    Science.gov (United States)

    Banerjee, Santanu; Isaacman-Beck, Jesse; Schneider, Valerie A; Granato, Michael

    2013-01-01

    During vertebrate development, trunk neural crest cells delaminate along the entire length of the dorsal neural tube and initially migrate as a non-segmented sheet. As they enter the somites, neural crest cells rearrange into spatially restricted segmental streams. Extracellular matrix components are likely to play critical roles in this transition from a sheet-like to a stream-like mode of migration, yet the extracellular matrix components and their modifying enzymes critical for this transition are largely unknown. Here, we identified the glycosyltransferase Lh3, known to modify extracellular matrix components, and its presumptive substrate Collagen18A1, to provide extrinsic signals critical for neural crest cells to transition from a sheet-like migration behavior to migrating as a segmental stream. Using live cell imaging we show that in lh3 null mutants, neural crest cells fail to transition from a sheet to a stream, and that they consequently enter the somites as multiple streams, or stall shortly after entering the somites. Moreover, we demonstrate that transgenic expression of lh3 in a small subset of somitic cells adjacent to where neural crest cells switch from sheet to stream migration restores segmental neural crest cell migration. Finally, we show that knockdown of the presumptive Lh3 substrate Collagen18A1 recapitulates the neural crest cell migration defects observed in lh3 mutants, consistent with the notion that Lh3 exerts its effect on neural crest cell migration by regulating post-translational modifications of Collagen18A1. Together these data suggest that Lh3-Collagen18A1 dependent ECM modifications regulate the transition of trunk neural crest cells from a non-segmental sheet like migration mode to a segmental stream migration mode.

  2. A novel role for MuSK and non-canonical Wnt signaling during segmental neural crest cell migration.

    Science.gov (United States)

    Banerjee, Santanu; Gordon, Laura; Donn, Thomas M; Berti, Caterina; Moens, Cecilia B; Burden, Steven J; Granato, Michael

    2011-08-01

    Trunk neural crest cells delaminate from the dorsal neural tube as an uninterrupted sheet; however, they convert into segmentally organized streams before migrating through the somitic territory. These neural crest cell streams join the segmental trajectories of pathfinding spinal motor axons, suggesting that interactions between these two cell types might be important for neural crest cell migration. Here, we show that in the zebrafish embryo migration of both neural crest cells and motor axons is temporally synchronized and spatially restricted to the center of the somite, but that motor axons are dispensable for segmental neural crest cell migration. Instead, we find that muscle-specific receptor kinase (MuSK) and its putative ligand Wnt11r are crucial for restricting neural crest cell migration to the center of each somite. Moreover, we find that blocking planar cell polarity (PCP) signaling in somitic muscle cells also results in non-segmental neural crest cell migration. Using an F-actin biosensor we show that in the absence of MuSK neural crest cells fail to retract non-productive leading edges, resulting in non-segmental migration. Finally, we show that MuSK knockout mice display similar neural crest cell migration defects, suggesting a novel, evolutionarily conserved role for MuSK in neural crest migration. We propose that a Wnt11r-MuSK dependent, PCP-like pathway restricts neural crest cells to their segmental path.

  3. 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.

  4. 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.

  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

    Summary 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. PMID:25986498

  6. Elk3 is essential for the progression from progenitor to definitive neural crest cell.

    Science.gov (United States)

    Rogers, Crystal D; Phillips, Jacquelyn L; Bronner, Marianne E

    2013-02-15

    Elk3/Net/Sap2 (here referred to as Elk3) is an Ets ternary complex transcriptional repressor known for its involvement in angiogenesis during embryonic development. Although Elk3 is expressed in various tissues, additional roles for the protein outside of vasculature development have yet to be reported. Here, we characterize the early spatiotemporal expression pattern of Elk3 in the avian embryo using whole mount in situ hybridization and quantitative RT-PCR and examine the effects of its loss of function on neural crest development. At early stages, Elk3 is expressed in the head folds, head mesenchyme, intersomitic vessels, and migratory cranial neural crest (NC) cells. Loss of the Elk3 protein results in the retention of Pax7+ precursors in the dorsal neural tube that fail to upregulate neural crest specifier genes, FoxD3, Sox10 and Snail2, resulting in embryos with severe migration defects. The results putatively place Elk3 downstream of neural plate border genes, but upstream of neural crest specifier genes in the neural crest gene regulatory network (NC-GRN), suggesting that it is critical for the progression from progenitor to definitive neural crest cell. PMID:23266330

  7. Live image profiling of neural crest lineages in zebrafish transgenic lines.

    Science.gov (United States)

    Kwak, Jina; Park, Ok Kyu; Jung, Yoo Jung; Hwang, Byung Joon; Kwon, Seung-Hae; Kee, Yun

    2013-03-01

    Zebrafish transgenic lines are important experimental tools for lineage tracing and imaging studies. It is crucial to precisely characterize the cell lineages labeled in transgenic lines to understand their limitations and thus properly interpret the data obtained from their use; only then can we confidently select a line appropriate for our particular research objectives. Here we profiled the cell lineages labeled in the closely related neural crest transgenic lines Tg(foxd3:GFP), Tg(sox10:eGFP) and Tg(sox10:mRFP). These fish were crossed to generate embryos, in which foxd3 and sox10 transgenic neural crest labeling could be directly compared at the cellular level using live confocal imaging. We have identified key differences in the cell lineages labeled in each line during early neural crest development and demonstrated that the most anterior cranial neural crest cells initially migrating out of neural tube at the level of forebrain and anterior midbrain express sox10:eGFP and sox10:mRFP, but not foxd3:GFP. This differential profile was robustly maintained in the differentiating progeny of the neural crest lineages until 3.5dpf. Our data will enable researchers to make an informed choice in selecting transgenic lines for future neural crest research.

  8. Induction of cranial and posterior trunk neural crest by exogenous retinoic acid in zebrafish

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Retinoic acid (RA) plays an important role in development of vertebrate embryos. We demonstrate impacts of exogenous RA on the formation of neural crest cells in zebrafish using specific neural crest markers sox9b and crestin. Treatment with all-trans RA at 10?7 mmol/L at 50% epiboly induces sox9b expression in the forebrain and crestin expression in the forebrain and midbrain, resulting in significant increase of pigment cells in the head derived from the cranial neural crest. In addition, RA treatment induces expression of sox9b and crestin in the caudal marginal cells of the neuroectoderm during early segmentation. Earlier commitment of these cells to the neural crest fate in the posterior margins leads to abnormal development of the posterior body, probably by preventing mingling of ventral derived and dorsal-derived cells during the formation of the tailbud.

  9. Dissecting early regulatory relationships in the lamprey neural crest gene network.

    Science.gov (United States)

    Nikitina, Natalya; Sauka-Spengler, Tatjana; Bronner-Fraser, Marianne

    2008-12-23

    The neural crest, a multipotent embryonic cell type, originates at the border between neural and nonneural ectoderm. After neural tube closure, these cells undergo an epithelial-mesenchymal transition, migrate to precise, often distant locations, and differentiate into diverse derivatives. Analyses of expression and function of signaling and transcription factors in higher vertebrates has led to the proposal that a neural crest gene regulatory network (NC-GRN) orchestrates neural crest formation. Here, we interrogate the NC-GRN in the lamprey, taking advantage of its slow development and basal phylogenetic position to resolve early inductive events, 1 regulatory step at the time. To establish regulatory relationships at the neural plate border, we assess relative expression of 6 neural crest network genes and effects of individually perturbing each on the remaining 5. The results refine an upstream portion of the NC-GRN and reveal unexpected order and linkages therein; e.g., lamprey AP-2 appears to function early as a neural plate border rather than a neural crest specifier and in a pathway linked to MsxA but independent of ZicA. These findings provide an ancestral framework for performing comparative tests in higher vertebrates in which network linkages may be more difficult to resolve because of their rapid development. PMID:19104059

  10. Dissecting early regulatory relationships in the lamprey neural crest gene network.

    Science.gov (United States)

    Nikitina, Natalya; Sauka-Spengler, Tatjana; Bronner-Fraser, Marianne

    2008-12-23

    The neural crest, a multipotent embryonic cell type, originates at the border between neural and nonneural ectoderm. After neural tube closure, these cells undergo an epithelial-mesenchymal transition, migrate to precise, often distant locations, and differentiate into diverse derivatives. Analyses of expression and function of signaling and transcription factors in higher vertebrates has led to the proposal that a neural crest gene regulatory network (NC-GRN) orchestrates neural crest formation. Here, we interrogate the NC-GRN in the lamprey, taking advantage of its slow development and basal phylogenetic position to resolve early inductive events, 1 regulatory step at the time. To establish regulatory relationships at the neural plate border, we assess relative expression of 6 neural crest network genes and effects of individually perturbing each on the remaining 5. The results refine an upstream portion of the NC-GRN and reveal unexpected order and linkages therein; e.g., lamprey AP-2 appears to function early as a neural plate border rather than a neural crest specifier and in a pathway linked to MsxA but independent of ZicA. These findings provide an ancestral framework for performing comparative tests in higher vertebrates in which network linkages may be more difficult to resolve because of their rapid development.

  11. 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 ...

  12. An exclusively mesodermal origin of fin mesenchyme demonstrates that zebrafish trunk neural crest does not generate ectomesenchyme.

    Science.gov (United States)

    Lee, Raymond Teck Ho; Knapik, Ela W; Thiery, Jean Paul; Carney, Thomas J

    2013-07-01

    The neural crest is a multipotent stem cell population that arises from the dorsal aspect of the neural tube and generates both non-ectomesenchymal (melanocytes, peripheral neurons and glia) and ectomesenchymal (skeletogenic, odontogenic, cartilaginous and connective tissue) derivatives. In amniotes, only cranial neural crest generates both classes, with trunk neural crest restricted to non-ectomesenchyme. By contrast, it has been suggested that anamniotes might generate derivatives of both classes at all axial levels, with trunk neural crest generating fin osteoblasts, scale mineral-forming cells and connective tissue cells; however, this has not been fully tested. The cause and evolutionary significance of this cranial/trunk dichotomy, and its absence in anamniotes, are debated. Recent experiments have disputed the contribution of fish trunk neural crest to fin osteoblasts and scale mineral-forming cells. This prompted us to test the contribution of anamniote trunk neural crest to fin connective tissue cells. Using genetics-based lineage tracing in zebrafish, we find that these fin mesenchyme cells derive entirely from the mesoderm and that neural crest makes no contribution. Furthermore, contrary to previous suggestions, larval fin mesenchyme cells do not generate the skeletogenic cells of the adult fin, but persist to form fibroblasts associated with adult fin rays. Our data demonstrate that zebrafish trunk neural crest does not generate ectomesenchymal derivatives and challenge long-held ideas about trunk neural crest fate. These findings have important implications for the ontogeny and evolution of the neural crest.

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Erika Kague

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

  16. Substrate-mediated reprogramming of human fibroblasts into neural crest stem-like cells and their applications in neural repair.

    Science.gov (United States)

    Tseng, Ting-Chen; Hsieh, Fu-Yu; Dai, Niann-Tzyy; Hsu, Shan-Hui

    2016-09-01

    Cell- and gene-based therapies have emerged as promising strategies for treating neurological diseases. The sources of neural stem cells are limited while the induced pluripotent stem (iPS) cells have risk of tumor formation. Here, we proposed the generation of self-renewable, multipotent, and neural lineage-related neural crest stem-like cells by chitosan substrate-mediated gene transfer of a single factor forkhead box D3 (FOXD3) for the use in neural repair. A simple, non-toxic, substrate-mediated method was applied to deliver the naked FOXD3 plasmid into human fibroblasts. The transfection of FOXD3 increased cell proliferation and up-regulated the neural crest marker genes (FOXD3, SOX2, and CD271), stemness marker genes (OCT4, NANOG, and SOX2), and neural lineage-related genes (Nestin, β-tubulin and GFAP). The expression levels of stemness marker genes and neural crest maker genes in the FOXD3-transfected fibroblasts were maintained until the fifth passage. The FOXD3 reprogrammed fibroblasts based on the new method significantly rescued the neural function of the impaired zebrafish. The chitosan substrate-mediated delivery of naked plasmid showed feasibility in reprogramming somatic cells. Particularly, the FOXD3 reprogrammed fibroblasts hold promise as an easily accessible cellular source with neural crest stem-like behavior for treating neural diseases in the future. PMID:27341268

  17. A robust method to derive functional neural crest cells from human pluripotent stem cells.

    Science.gov (United States)

    Kreitzer, Faith R; Salomonis, Nathan; Sheehan, Alice; Huang, Miller; Park, Jason S; Spindler, Matthew J; Lizarraga, Paweena; Weiss, William A; So, Po-Lin; Conklin, Bruce R

    2013-01-01

    Neural crest (NC) cells contribute to the development of many complex tissues of all three germ layers during embryogenesis, and its abnormal development accounts for several congenital birth defects. Generating NC cells-including specific subpopulations such as cranial, cardiac, and trunk NC cells-from human pluripotent stem cells will provide a valuable model system to study human development and disease. Here, we describe a rapid and robust NC differentiation method called "LSB-short" that is based on dual SMAD pathway inhibition. This protocol yields high percentages of NC cell populations from multiple human induced pluripotent stem and human embryonic stem cell lines in 8 days. The resulting cells can be propagated easily, retain NC marker expression over multiple passages, and can spontaneously differentiate into several NC-derived cell lineages, including smooth muscle cells, peripheral neurons, and Schwann cells. NC cells generated by this method represent cranial, cardiac and trunk NC subpopulations based on global gene expression analyses, are similar to in vivo analogues, and express a common set of NC alternative isoforms. Functionally, they are also able to migrate appropriately in response to chemoattractants such as SDF-1, FGF8b, and Wnt3a. By yielding NC cells that likely represent all NC subpopulations in a shorter time frame than other published methods, our LSB-short method provides an ideal model system for further studies of human NC development and disease. PMID:23862100

  18. Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis.

    Science.gov (United States)

    Chai, Y; Jiang, X; Ito, Y; Bringas, P; Han, J; Rowitch, D H; Soriano, P; McMahon, A P; Sucov, H M

    2000-04-01

    Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indelibly marking the progeny of the cranial neural crest during tooth and mandible development. In the first mouse line, Cre recombinase is expressed under the control of the Wnt1 promoter as a transgene. Significantly, Wnt1 transgene expression is limited to the migrating neural crest cells that are derived from the dorsal CNS. The second mouse line, the ROSA26 conditional reporter (R26R), serves as a substrate for the Cre-mediated recombination. Using this two-component genetic system, we have systematically followed the migration and differentiation of the cranial neural crest (CNC) cells from E9.5 to 6 weeks after birth. Our results demonstrate, for the first time, that CNC cells contribute to the formation of condensed dental mesenchyme, dental papilla, odontoblasts, dentine matrix, pulp, cementum, periodontal ligaments, chondrocytes in Meckel's cartilage, mandible, the articulating disc of temporomandibular joint and branchial arch nerve ganglia. More importantly, there is a dynamic distribution of CNC- and non-CNC-derived cells during tooth and mandibular morphogenesis. These results are a first step towards a comprehensive understanding of neural crest cell migration and differentiation during mammalian craniofacial development. Furthermore, this transgenic model also provides a new tool for cell lineage analysis and genetic manipulation of neural-crest-derived components in normal and abnormal embryogenesis. PMID:10725243

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

    Lifescience Database Archive (English)

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  20. File list: ALL.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: ALL.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.PSC.10.AllAg.hESC_derived_neural_crests hg19 All antigens Pluripotent stem cell hESC derived neural cres...X059364,SRX1091530 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.PSC.10.AllAg.hESC_derived_neural_crests.bed ...

  2. Local increase level of chondroitin sulfate induces changes in the rhombencephalic neural crest migration.

    Science.gov (United States)

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

    1998-03-01

    Numerous studies suggest that chondroitin sulfate proteoglycan (CSPG) inhibits neural crest cells (NCC) migration at the trunk level. However, its action on the cephalic neural crest is not clear. To determine this action, we have microinjected 0.5 nl of different concentrations of chondroitin sulfate (CS) at the anterior rhombencephalon level in 9 stage chick embryos, as well as subgerminally administering beta-D-xyloside to 8 stage chick embryos. Beta-D-xyloside disrupts CSPG synthesis, producing an increase in CS free chains in several embryonal anlages. Chondroitin sulfate microinjected embryos and beta-D xyloside treated embryos were reincubated until attaining 12 stage. Results obtained for both experimental groups were similar. Immunoreactivity with HNK-1 antibody revealed that NCC did not migrate, remaining near the rhombencephalon dorsal wall; in addition, several NCC did not separate from the neural fold, becoming invaginated towards the rhombencephalon cavity. Our findings indicate that an increase in CS free chains in cephalic neural crest migratory routes not only disrupts their migration, but also impedes delamination and detachment of the rhombencephalic neuroepithelium NCC. These data suggest that the inhibitory action upon the neural crest migration attributed to CSPG may rest on its glycosaminoglycan (GAG). We cannot, however, rule out the possibility that increases in other GAGs apart from CS, may produce similar effects on neural crest migration. PMID:9551866

  3. File list: Oth.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Oth.PSC.10.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Oth.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Oth.PSC.50.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

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

    Directory of Open Access Journals (Sweden)

    M La Noce

    2014-10-01

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

  8. Signi fi cance of Neural Crest in Tooth Development: The Molecular Signature

    Directory of Open Access Journals (Sweden)

    VP Jayasekharan

    2014-07-01

    Full Text Available The neural crest originates from cells located along the lateral margins of the neural plate. Neural crest cells arise as the result of an inductive action by the non-neural ectoderm adjacent to the neural plate and possibly by nearby mesoderm as well. As the neural tube forms, a group of cells separate from the neuro- ectoderm. These cells have the capacity to migrate and differen- tiate extensively within the developing embryo and they are the basis of structures such as spinal sensory ganglia, sympathetic neurons, Schwann cells, pigment cells and meninges. Speci fi c interactions occur during the development of tooth and recent research has concentrated more on the molecular aspects of these interactions. Thus, it is highly imperative to understand and digress the complex mechanisms involved in these processes

  9. Characterization of an individual neural crest-like cell lineage in the invertebrate chordate Ciona intestinalis

    OpenAIRE

    Cone, Angela C.

    2008-01-01

    During embryogenesis, all chordate embryos undergo neurulation to form a dorsal, hollow nerve cord. Neural crest cells (NCC), considered a vertebrate innovation, arise during neurulation and later differentiate into a multitude of tissues that account for much of the structural complexity that distinguishes craniates from invertebrate chordates [1, 2]. NCCs are induced and specified at the border of the neural and non-neural ectoderm by a complex network of inductive signals and transcription...

  10. [Progress in the study of syndromic hearing loss resulted from neural crest abnormalities].

    Science.gov (United States)

    Yalan, Liu; Hua, Zhang; Yong, Feng

    2014-11-01

    More than 400 types of syndromic hearing loss (SHL) have been reported so far, in which Waardenburg syndrome (WS), congenital microtia syndrome (CMS), and large vestibular aqueduct syndrome (LVAS) are the most common ones in clinic. However, it is difficult to study the genetic basis and pathogenesis of SHL in a systematical way because of the strong clinical and genetic heterogeneity of SHL. Dysfunction of neural crest cells (NCC), which are caused by the gene interaction network extended from SOX10 and PAX3, are relevant to the phenotype of WS, CMS and LVAS. Our previous study also confirmed that the gene network was involved in the pathogenesis of WS. In this review, we summarize research progress in the pathogenic mechanisms of SHL resulted from defects in neural crest decelopment, and provide the gene interaction network of neural crest abnormalities resulting in SHL, and hope to provide research ideas and theoretical basis for the systematical study on pathogenesis of common SHL. PMID:25567871

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

    Directory of Open Access Journals (Sweden)

    Christine Cheung

    2014-10-01

    Full Text Available There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden.

  12. Radionuclide diagnosis and therapy of neural crest tumors using iodine-131 metaiodobenzylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A.; Voute, P.A.; de Kraker, J.; Marcuse, H.R.

    1987-03-01

    The successful application of (/sup 131/I)metaiodobenzylguanidine (MIBG) in diagnosis and therapy of pheochromocytoma has led to its use in other tumors which derive from the neural crest and potentially concentrate this radiopharmaceutical as well. In the present series, (/sup 131/)MIBG total-body scintigraphy was used for detection of neuroblastoma in 47 patients and 47 cases of other neural crest tumors. The method was found to be as reliable in neuroblastoma (sensitivity 95%, specificity 100%), as it is in pheochromocytoma. Although other neural crest tumors may concentrate (/sup 131/I)MIBG, this is not a consistent finding; however, it is useful to investigate which tumors do, as this may provide an alternative treatment modality for some patients. Although followup is still very short, preliminary results of therapeutic use of (/sup 131/I) MIBG in 21 patients indicate that this treatment modality may be effective in neuroblastoma and malignant pheochromocytoma.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. File list: ALL.PSC.20.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.PSC.20.AllAg.hESC_derived_neural_crests hg19 All antigens Pluripotent stem cell hESC derived...X1091539,SRX059364 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

  16. File list: His.PSC.05.AllAg.hESC_derived_neural_crests [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.PSC.05.AllAg.hESC_derived_neural_crests hg19 Histone Pluripotent stem cell hESC derived...13,SRX1091515,SRX059363,SRX059364 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

  17. Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

    Science.gov (United States)

    Glejzer, A; Laudet, E; Leprince, P; Hennuy, B; Poulet, C; Shakhova, O; Sommer, L; Rogister, B; Wislet-Gendebien, S

    2011-06-01

    Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities. PMID:20976520

  18. Cdon promotes neural crest migration by regulating N-cadherin localization.

    Science.gov (United States)

    Powell, Davalyn R; Williams, Jason S; Hernandez-Lagunas, Laura; Salcedo, Ernesto; O'Brien, Jenean H; Artinger, Kristin Bruk

    2015-11-15

    Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.

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

    NARCIS (Netherlands)

    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.

    2016-01-01

    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 dif

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

    NARCIS (Netherlands)

    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

    2016-01-01

    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 dif

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

    International Nuclear Information System (INIS)

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

  2. Gene regulatory evolution and the origin of macroevolutionary novelties: insights from the neural crest

    OpenAIRE

    Van Otterloo, Eric; Robert A Cornell; Medeiros, Daniel Meulemans; Garnett, Aaron T.

    2013-01-01

    The appearance of novel anatomic structures during evolution is driven by changes to the networks of transcription factors, signaling pathways, and downstream effector genes controlling development. The nature of the changes to these developmental gene regulatory networks (GRNs) is poorly understood. A striking test case is the evolution of the GRN controlling development of the neural crest (NC). NC cells emerge from the neural plate border (NPB) and contribute to multiple adult structures. ...

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

    Directory of Open Access Journals (Sweden)

    Matthew J Anderson

    2016-05-01

    Full Text Available 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

  4. miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells

    Institute of Scientific and Technical Information of China (English)

    Yuxin Ni; Kaizhi Zhang; Xuejuan Liu; Tingting Yang; Baixiang Wang; Li Fu; Lan A; Yanmin Zhou

    2014-01-01

    Hair follicle-derived neural crest stem cells can be induced to differentiate into Schwann cells in vivo and in vitro. However, the underlying regulatory mechanism during cell differentiation remains poorly understood. This study isolated neural crest stem cells from human hair folli-cles and induced them to differentiate into Schwann cells. Quantitative RT-PCR showed that microRNA (miR)-21 expression was gradually increased during the differentiation of neural crest stem cells into Schwann cells. After transfection with the miR-21 agonist (agomir-21), the differentiation capacity of neural crest stem cells was enhanced. By contrast, after transfection with the miR-21 antagonist (antagomir-21), the differentiation capacity was attenuated. Further study results showed that SOX-2 was an effective target of miR-21. Without compromising SOX2 mRNA expression, miR-21 can down-regulate SOX protein expression by binding to the 3′-UTR of miR-21 mRNA. Knocking out the SOX2 gene from the neural crest stem cells significantly reversed the antagomir-21 inhibition of neural crest stem cells differentiating into Schwann cells. The results suggest that miR-21 expression was increased during the differentiation of neural crest stem cells into Schwann cells and miR-21 promoted the differentiation through down-regu-lating SOX protein expression by binding to the 3′-UTR of SOX2 mRNA.

  5. 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

  6. The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification.

    Science.gov (United States)

    Hatch, Victoria L; Marin-Barba, Marta; Moxon, Simon; Ford, Christopher T; Ward, Nicole J; Tomlinson, Matthew L; Desanlis, Ines; Hendry, Adam E; Hontelez, Saartje; van Kruijsbergen, Ila; Veenstra, Gert Jan C; Münsterberg, Andrea E; Wheeler, Grant N

    2016-08-15

    Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a 'gate-keeper' for the correct temporal and spatial development of the neural crest. PMID:27343897

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Sox10-dependent neural crest origin of olfactory microvillous neurons in zebrafish.

    Science.gov (United States)

    Saxena, Ankur; Peng, Brian N; Bronner, Marianne E

    2013-03-19

    The sense of smell in vertebrates is detected by specialized sensory neurons derived from the peripheral nervous system. Classically, it has been presumed that the olfactory placode forms all olfactory sensory neurons. In contrast, we show that the cranial neural crest is the primary source of microvillous sensory neurons within the olfactory epithelium of zebrafish embryos. Using photoconversion-based fate mapping and live cell tracking coupled with laser ablation, we followed neural crest precursors as they migrated from the neural tube to the nasal cavity. A subset that coexpressed Sox10 protein and a neurogenin1 reporter ingressed into the olfactory epithelium and differentiated into microvillous sensory neurons. Timed loss-of-function analysis revealed a critical role for Sox10 in microvillous neurogenesis. Taken together, these findings directly demonstrate a heretofore unknown contribution of the cranial neural crest to olfactory sensory neurons in zebrafish and provide important insights into the assembly of the nascent olfactory system. DOI:http://dx.doi.org/10.7554/eLife.00336.001.

  9. 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

    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

  10. Neural crest and mesoderm lineage-dependent gene expression in orofacial development.

    Science.gov (United States)

    Bhattacherjee, Vasker; Mukhopadhyay, Partha; Singh, Saurabh; Johnson, Charles; Philipose, John T; Warner, Courtney P; Greene, Robert M; Pisano, M Michele

    2007-06-01

    The present study utilizes a combination of genetic labeling/selective isolation of pluripotent embryonic progenitor cells, and oligonucleotide-based microarray technology, to delineate and compare the "molecular fingerprint" of two mesenchymal cell populations from distinct lineages in the developing embryonic orofacial region. The first branchial arches-bi-lateral tissue primordia that flank the primitive oral cavity-are populated by pluripotent mesenchymal cells from two different lineages: neural crest (neuroectoderm)- and mesoderm-derived mesenchymal cells. These cells give rise to all of the connective tissue elements (bone, cartilage, smooth and skeletal muscle, dentin) of the orofacial region (maxillary and mandibular portion), as well as neurons and glia associated with the cranial ganglia, among other tissues. In the present study, neural crest- and mesoderm-derived mesenchymal cells were selectively isolated from the first branchial arch of gestational day 9.5 mouse embryos using laser capture microdissection (LCM). The two different embryonic cell lineages were distinguished through utilization of a novel two component transgenic mouse model (Wnt1Cre/ZEG) in which the neural crest cells and their derivatives are indelibly marked (i.e., expressing enhanced green fluorescent protein, EGFP) throughout the pre- and post-natal lifespan of the organism. EGFP-labeled neural crest-derived, and non-fluorescent mesoderm-derived mesenchymal cells from the first branchial arch were visualized in frozen tissue sections from gestational day 9.5 mouse embryos and independently isolated by LCM under epifluorescence optics. RNA was extracted from the two populations of LCM-procured cells, and amplified by double-stranded cDNA synthesis and in vitro transcription. Gene expression profiles of the two progenitor cell populations were generated via hybridization of the cell-type specific cRNA samples to oligo-based GeneChip microarrays. Comparison of gene expression

  11. Neural crest-mediated bone resorption is a determinant of species-specific jaw length

    OpenAIRE

    Ealba, Erin L.; Jheon, Andrew H.; Hall, Jane; Curantz, Camille; Butcher, Kristin D.; Schneider, Richard A

    2015-01-01

    Precise control of jaw length during development is crucial for proper form and function. Previously we have shown that in birds, neural crest mesenchyme (NCM) confers species-specific size and shape to the beak by regulating molecular and histological programs for the induction and deposition of cartilage and bone. Here we reveal that a hitherto unrecognized but similarly essential mechanism for establishing jaw length is the ability of NCM to mediate bone resorption. Osteoclasts are conside...

  12. Adipose Stromal Cells Contain Phenotypically Distinct Adipogenic Progenitors Derived from Neural Crest

    OpenAIRE

    Yoshihiro Sowa; Tetsuya Imura; Toshiaki Numajiri; Kosuke Takeda; Yo Mabuchi; Yumi Matsuzaki; Kenichi Nishino

    2013-01-01

    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 contain...

  13. Feeder-free Derivation of Neural Crest Progenitor Cells from Human Pluripotent Stem Cells

    OpenAIRE

    Zeltner, Nadja; Lafaille, Fabien G.; Fattahi, Faranak; Studer, Lorenz

    2014-01-01

    Human pluripotent stem cells (hPSCs) have great potential for studying human embryonic development, for modeling human diseases in the dish and as a source of transplantable cells for regenerative applications after disease or accidents. Neural crest (NC) cells are the precursors for a large variety of adult somatic cells, such as cells from the peripheral nervous system and glia, melanocytes and mesenchymal cells. They are a valuable source of cells to study aspects of human embryonic develo...

  14. Analysis of neural crest-derived clones reveals novel aspects of facial development.

    Science.gov (United States)

    Kaucka, Marketa; Ivashkin, Evgeny; Gyllborg, Daniel; Zikmund, Tomas; Tesarova, Marketa; Kaiser, Jozef; Xie, Meng; Petersen, Julian; Pachnis, Vassilis; Nicolis, Silvia K; Yu, Tian; Sharpe, Paul; Arenas, Ernest; Brismar, Hjalmar; Blom, Hans; Clevers, Hans; Suter, Ueli; Chagin, Andrei S; Fried, Kaj; Hellander, Andreas; Adameyko, Igor

    2016-08-01

    Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth. PMID:27493992

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

    Directory of Open Access Journals (Sweden)

    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

  16. Induction of neural crest in Xenopus by transcription factor AP2α

    OpenAIRE

    Luo, Ting; Lee, Young-Hoon; Saint-Jeannet, Jean-Pierre; Sargent, Thomas D.

    2003-01-01

    We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2α is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2α is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by exp...

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

    Directory of Open Access Journals (Sweden)

    Tsutomu Motohashi

    2016-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Hartley Rebecca S

    2010-01-01

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

  19. Meis3 is required for neural crest invasion of the gut during zebrafish enteric nervous system development.

    Science.gov (United States)

    Uribe, Rosa A; Bronner, Marianne E

    2015-11-01

    During development, vagal neural crest cells fated to contribute to the enteric nervous system migrate ventrally away from the neural tube toward and along the primitive gut. The molecular mechanisms that regulate their early migration en route to and entry into the gut remain elusive. Here we show that the transcription factor meis3 is expressed along vagal neural crest pathways. Meis3 loss of function results in a reduction in migration efficiency, cell number, and the mitotic activity of neural crest cells in the vicinity of the gut but has no effect on neural crest or gut specification. Later, during enteric nervous system differentiation, Meis3-depleted embryos exhibit colonic aganglionosis, a disorder in which the hindgut is devoid of neurons. Accordingly, the expression of Shh pathway components, previously shown to have a role in the etiology of Hirschsprung's disease, was misregulated within the gut after loss of Meis3. Taken together, these findings support a model in which Meis3 is required for neural crest proliferation, migration into, and colonization of the gut such that its loss leads to severe defects in enteric nervous system development.

  20. The different effects on cranial and trunk neural crest cell behaviour following exposure to a low concentration of alcohol in vitro.

    Science.gov (United States)

    Czarnobaj, Joanna; Bagnall, Keith M; Bamforth, J Steven; Milos, Nadine C

    2014-05-01

    Embryonic neural crest cells give rise to large regions of the face and peripheral nervous system. Exposure of these cells to high alcohol concentrations leads to cell death in the craniofacial region resulting in facial defects. However, the effects of low concentrations of alcohol on neural crest cells are not clear. In this study, cranial neural crest cells from Xenopus laevis were cultured in an ethanol concentration approximately equivalent to one drink. Techniques were developed to study various aspects of neural crest cell behaviour and a number of cellular parameters were quantified. In the presence of alcohol, a significant number of cranial neural crest cells emigrated from the explant on fibronectin but the liberation of individual cells was delayed. The cells also remained close to the explant and their morphology changed. Cranial neural crest cells did not grow on Type 1 collagen. For the purposes of comparison, the behaviour of trunk neural crest cells was also studied. The presence of alcohol correlated with increased retention of single cells on fibronectin but left other parameters unchanged. The behaviour of trunk neural crest cells growing on Type 1 collagen in the presence of alcohol did not differ from controls. Low concentrations of alcohol therefore significantly affected both cranial and trunk neural crest cells, with a wider variety of effects on cells from the cranial as opposed to the trunk region. The results suggest that low concentrations of alcohol may be more detrimental to early events in organ formation than currently suspected.

  1. Canonical Wnt activity regulates trunk neural crest delamination linking BMP/noggin signaling with G1/S transition.

    Science.gov (United States)

    Burstyn-Cohen, Tal; Stanleigh, Jonathan; Sela-Donenfeld, Dalit; Kalcheim, Chaya

    2004-11-01

    Delamination of premigratory neural crest cells depends on a balance between BMP/noggin and on successful G1/S transition. Here, we report that BMP regulates G1/S transition and consequent crest delamination through canonical Wnt signaling. Noggin overexpression inhibits G1/S transition and blocking G1/S abrogates BMP-induced delamination; moreover, transcription of Wnt1 is stimulated by BMP and by the developing somites, which concomitantly inhibit noggin production. Interfering with beta-catenin and LEF/TCF inhibits G1/S transition, neural crest delamination and transcription of various BMP-dependent genes, which include Cad6B, Pax3 and Msx1, but not that of Slug, Sox9 or FoxD3. Hence, we propose that developing somites inhibit noggin transcription in the dorsal tube, resulting in activation of BMP and consequent Wnt1 production. Canonical Wnt signaling in turn stimulates G1/S transition and generation of neural crest cell motility independently of its proposed role in earlier neural crest specification. PMID:15456730

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

    International Nuclear Information System (INIS)

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

  3. IKAP/Elp1 is required in vivo for neurogenesis and neuronal survival, but not for neural crest migration.

    Directory of Open Access Journals (Sweden)

    Barbara J Hunnicutt

    Full Text Available Familial Dysautonomia (FD; Hereditary Sensory Autonomic Neuropathy; HSAN III manifests from a failure in development of the peripheral sensory and autonomic nervous systems. The disease results from a point mutation in the IKBKAP gene, which encodes the IKAP protein, whose function is still unresolved in the developing nervous system. Since the neurons most severely depleted in the disease derive from the neural crest, and in light of data identifying a role for IKAP in cell motility and migration, it has been suggested that FD results from a disruption in neural crest migration. To determine the function of IKAP during development of the nervous system, we (1 first determined the spatial-temporal pattern of IKAP expression in the developing peripheral nervous system, from the onset of neural crest migration through the period of programmed cell death in the dorsal root ganglia, and (2 using RNAi, reduced expression of IKBKAP mRNA in the neural crest lineage throughout the process of dorsal root ganglia (DRG development in chick embryos in ovo. Here we demonstrate that IKAP is not expressed by neural crest cells and instead is expressed as neurons differentiate both in the CNS and PNS, thus the devastation of the PNS in FD could not be due to disruptions in neural crest motility or migration. In addition, we show that alterations in the levels of IKAP, through both gain and loss of function studies, perturbs neuronal polarity, neuronal differentiation and survival. Thus IKAP plays pleiotropic roles in both the peripheral and central nervous systems.

  4. Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development.

    Science.gov (United States)

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

    2013-08-01

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

  5. A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells.

    Science.gov (United States)

    Nitzan, Erez; Krispin, Shlomo; Pfaltzgraff, Elise R; Klar, Avihu; Labosky, Patricia A; Kalcheim, Chaya

    2013-06-01

    Understanding when and how multipotent progenitors segregate into diverse fates is a key question during embryonic development. The neural crest (NC) is an exemplary model system with which to investigate the dynamics of progenitor cell specification, as it generates a multitude of derivatives. Based on 'in ovo' lineage analysis, we previously suggested an early fate restriction of premigratory trunk NC to generate neural versus melanogenic fates, yet the timing of fate segregation and the underlying mechanisms remained unknown. Analysis of progenitors expressing a Foxd3 reporter reveals that prospective melanoblasts downregulate Foxd3 and have already segregated from neural lineages before emigration. When this downregulation is prevented, late-emigrating avian precursors fail to upregulate the melanogenic markers Mitf and MC/1 and the guidance receptor Ednrb2, generating instead glial cells that express P0 and Fabp. In this context, Foxd3 lies downstream of Snail2 and Sox9, constituting a minimal network upstream of Mitf and Ednrb2 to link melanogenic specification with migration. Consistent with the gain-of-function data in avians, loss of Foxd3 function in mouse NC results in ectopic melanogenesis in the dorsal tube and sensory ganglia. Altogether, Foxd3 is part of a dynamically expressed gene network that is necessary and sufficient to regulate fate decisions in premigratory NC. Their timely downregulation in the dorsal neural tube is thus necessary for the switch between neural and melanocytic phases of NC development.

  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. PMID:26755698

  7. Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull.

    Science.gov (United States)

    Wada, Naoyuki; Javidan, Yashar; Nelson, Sarah; Carney, Thomas J; Kelsh, Robert N; Schilling, Thomas F

    2005-09-01

    Neural crest cells that form the vertebrate head skeleton migrate and interact with surrounding tissues to shape the skull, and defects in these processes underlie many human craniofacial syndromes. Signals at the midline play a crucial role in the development of the anterior neurocranium, which forms the ventral braincase and palate, and here we explore the role of Hedgehog (Hh) signaling in this process. Using sox10:egfp transgenics to follow neural crest cell movements in the living embryo, and vital dye labeling to generate a fate map, we show that distinct populations of neural crest form the two main cartilage elements of the larval anterior neurocranium: the paired trabeculae and the midline ethmoid. By analyzing zebrafish mutants that disrupt sonic hedgehog (shh) expression, we demonstrate that shh is required to specify the movements of progenitors of these elements at the midline, and to induce them to form cartilage. Treatments with cyclopamine, to block Hh signaling at different stages, suggest that although requirements in morphogenesis occur during neural crest migration beneath the brain, requirements in chondrogenesis occur later, as cells form separate trabecular and ethmoid condensations. Cell transplantations indicate that these also reflect different sources of Shh, one from the ventral neural tube that controls trabecular morphogenesis and one from the oral ectoderm that promotes chondrogenesis. Our results suggest a novel role for Shh in the movements of neural crest cells at the midline, as well as in their differentiation into cartilage, and help to explain why both skeletal fusions and palatal clefting are associated with the loss of Hh signaling in holoprosencephalic humans.

  8. 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-...

  9. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    Full Text Available Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC as mixed populations of cells including mesenchymal (MSC and neural crest stem cells (NCSC. Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application.

  10. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Poulet, Christophe; Neirinckx, Virginie; Hennuy, Benoit; Swingland, James T; Laudet, Emerence; Sommer, Lukas; Shakova, Olga; Bours, Vincent; Rogister, Bernard

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the transformation of NCSC into tumorigenic cells, after in vitro long-term passaging. Indeed, the characterization of 6 neural crest-derived clones revealed the presence of one tumorigenic clone. Transcriptomic analyses of this clone highlighted, among others, numerous cell cycle checkpoint modifications and chromosome 11q down-regulation (suggesting a deletion of chromosome 11q) compared with the other clones. Moreover, unsupervised analysis such as a dendrogram generated after agglomerative hierarchical clustering comparing several transcriptomic data showed important similarities between the tumorigenic neural crest-derived clone and mammary tumor cell lines. Altogether, it appeared that NCSC isolated from adult bone marrow represents a potential danger for cellular therapy, and consequently, we recommend that phenotypic, functional and genetic assays should be performed on bone marrow mesenchymal and neural crest stem cells before in vivo use, to demonstrate whether their biological properties, after ex vivo expansion, remain suitable for clinical application. PMID:23071568

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

    OpenAIRE

    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

    2013-01-01

    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...

  12. 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

  13. Cranial neural crest cells on the move: their roles in craniofacial development.

    Science.gov (United States)

    Cordero, Dwight R; Brugmann, Samantha; Chu, Yvonne; Bajpai, Ruchi; Jame, Maryam; Helms, Jill A

    2011-02-01

    The craniofacial region is assembled through the active migration of cells and the rearrangement and sculpting of facial prominences and pharyngeal arches, which consequently make it particularly susceptible to a large number of birth defects. Genetic, molecular, and cellular processes must be temporally and spatially regulated to culminate in the three-dimension structures of the face. The starting constituent for the majority of skeletal and connective tissues in the face is a pluripotent population of cells, the cranial neural crest cells (NCCs). In this review we discuss the newest scientific findings in the development of the craniofacial complex as related to NCCs. Furthermore, we present recent findings on NCC diseases called neurocristopathies and, in doing so, provide clinicians with new tools for understanding a growing number of craniofacial genetic disorders. PMID:21271641

  14. 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

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

    Science.gov (United States)

    Richardson, Jo; Gauert, Anton; Briones Montecinos, Luis; Fanlo, Lucía; Alhashem, Zainalabdeen Mohmammed; Assar, Rodrigo; Marti, Elisa; Kabla, Alexandre; Härtel, Steffen; Linker, Claudia

    2016-05-31

    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.

  16. 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

  17. Pigment pattern evolution by differential deployment of neural crest and post-embryonic melanophore lineages in Danio fishes.

    Science.gov (United States)

    Quigley, Ian K; Turner, Jessica M; Nuckels, Richard J; Manuel, Joan L; Budi, Erine H; MacDonald, Erin L; Parichy, David M

    2004-12-01

    Latent precursors or stem cells of neural crest origin are present in a variety of post-embryonic tissues. Although these cells are of biomedical interest for roles in human health and disease, their potential evolutionary significance has been underappreciated. As a first step towards elucidating the contributions of such cells to the evolution of vertebrate form, we investigated the relative roles of neural crest cells and post-embryonic latent precursors during the evolutionary diversification of adult pigment patterns in Danio fishes. These pigment patterns result from the numbers and arrangements of embryonic melanophores that are derived from embryonic neural crest cells, as well as from post-embryonic metamorphic melanophores that are derived from latent precursors of presumptive neural crest origin. In the zebrafish D. rerio, a pattern of melanophore stripes arises during the larval-to-adult transformation by the recruitment of metamorphic melanophores from latent precursors. Using a comparative approach in the context of new phylogenetic data, we show that adult pigment patterns in five additional species also arise from metamorphic melanophores, identifying this as an ancestral mode of adult pigment pattern development. By contrast, superficially similar adult stripes of D. nigrofasciatus (a sister species to D. rerio) arise by the reorganization of melanophores that differentiated at embryonic stages, with a diminished contribution from metamorphic melanophores. Genetic mosaic and molecular marker analyses reveal evolutionary changes that are extrinsic to D. nigrofasciatus melanophore lineages, including a dramatic reduction of metamorphic melanophore precursors. Finally, interspecific complementation tests identify a candidate genetic pathway for contributing to the evolutionary reduction in metamorphic melanophores and the increased contribution of early larval melanophores to D. nigrofasciatus adult pigment pattern development. These results

  18. 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. PMID:23382206

  19. Induction of neural crest in Xenopus by transcription factor AP2alpha.

    Science.gov (United States)

    Luo, Ting; Lee, Young-Hoon; Saint-Jeannet, Jean-Pierre; Sargent, Thomas D

    2003-01-21

    We report experiments with Xenopus laevis, using both intact embryos and ectodermal explants, showing that the transcription factor AP2alpha is positively regulated by bone morphogenetic protein (BMP) and Wnt signaling, and that this activation is an essential step in the induction of neural crest (NC). Ectopic expression of AP2alpha is sufficient to activate high-level expression of NC-specific genes such as Slug and Sox9, which can occur as isolated domains within the neural plate as well as by expansion of endogenous NC territories. AP2alpha also has the property of inducing NC in isolated ectoderm in which Wnt signaling is provided but BMP signaling is minimized by overexpression of chordin. Like other NC regulatory factors, activation of AP2alpha requires some attenuation of endogenous BMP signaling; however, this process occurs at a lower threshold for AP2alpha. Furthermore, AP2alpha expression domains are larger than for other NC factors. Loss-of-function experiments with antisense AP2alpha morpholino oligonucleotides result in severe reduction in the NC territory. These results support a central role for AP2alpha in NC induction. We propose a model in which AP2alpha expression, along with inactivation of NC inhibitory factors such as Dlx3, establish a feedback loop comprising AP2alpha, Sox9, and Slug, leading to and maintaining NC specification. PMID:12511599

  20. 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.

  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

    Directory of Open Access Journals (Sweden)

    Khadijeh Karbalaie

    2015-04-01

    Full Text Available Objective: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. IN VITRO PROPERTIES OF NEURAL CREST-DERIVED MULTIPOTENT STEM CELLS FROM A BULGE REGION OF WHISKER FOLLICLE

    Directory of Open Access Journals (Sweden)

    R. G. Vasyliev

    2014-08-01

    Full Text Available A culture method for multipotent neural crest-derived stem cell isolated from the bulge region of the hair follicle of whisker pad of adult mice has been described and their biological properties have been studied. It was shown that the cells possess a fibroblast-like morphology, they are nestin-positive and cytokeratin-negative, and also express the following surface markers: CD44, CD73, CD90 and Sca-1. This cell type shows the functional properties of stem cells in culture: clonogenicity, self-renewal, sphere-forming capacity and the ability to the directed multilineage differentiation. Due to these properties, neural crest-derived multipotent stem cells are promising for application in the regenerative medicine

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

    OpenAIRE

    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

    Background 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 CRIS...

  4. Evaluation of Developmental Toxicants and Signaling Pathways in a Functional Test Based on the Migration of Human Neural Crest Cells

    OpenAIRE

    Zimmer, Bastian; Lee, Gabsang; Balmer, Nina V.; Meganathan, Kesavan; Sachinidis, Agapios; Studer, Lorenz; Leist, Marcel

    2012-01-01

    Background: Information on the potential developmental toxicity (DT) of the majority of chemicals is scarce, and test capacities for further animal-based testing are limited. Therefore, new approaches with higher throughput are required. A screening strategy based on the use of relevant human cell types has been proposed by the U.S. Environmental Protection Agency and others. Because impaired neural crest (NC) function is one of the known causes for teratologic effects, testing of toxicant ef...

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

    Directory of Open Access Journals (Sweden)

    Brenda L Bohnsack

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

  6. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow

    OpenAIRE

    Sabine Wislet-Gendebien; Christophe Poulet; Virginie Neirinckx; Benoit Hennuy; Swingland, James T.; Emerence Laudet; Lukas Sommer; Olga Shakova; Vincent Bours; Bernard Rogister

    2012-01-01

    Bone marrow stromal cells are adult multipotent cells that represent an attractive tool in cellular therapy strategies. Several studies have reported that in vitro passaging of mesenchymal stem cells alters the functional and biological properties of those cells, leading to the accumulation of genetic aberrations. Recent studies described bone marrow stromal cells (BMSC) as mixed populations of cells including mesenchymal (MSC) and neural crest stem cells (NCSC). Here, we report the ...

  7. The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes.

    Science.gov (United States)

    Silver, Debra L; Leeds, Karen E; Hwang, Hun-Way; Miller, Emily E; Pavan, William J

    2013-03-15

    Melanoblasts are a population of neural crest-derived cells that generate the pigment-producing cells of our body. Defective melanoblast development and function underlies many disorders including Waardenburg syndrome and melanoma. Understanding the genetic regulation of melanoblast development will help elucidate the etiology of these and other neurocristopathies. Here we demonstrate that Magoh, a component of the exon junction complex, is required for normal melanoblast development. Magoh haploinsufficient mice are hypopigmented and exhibit robust genetic interactions with the transcription factor, Sox10. These phenotypes are caused by a marked reduction in melanoblast number beginning at mid-embryogenesis. Strikingly, while Magoh haploinsufficiency severely reduces epidermal melanoblasts, it does not significantly affect the number of dermal melanoblasts. These data indicate Magoh impacts melanoblast development by disproportionately affecting expansion of epidermal melanoblast populations. We probed the cellular basis for melanoblast reduction and discovered that Magoh mutant melanoblasts do not undergo increased apoptosis, but instead are arrested in mitosis. Mitotic arrest is evident in both Magoh haploinsufficient embryos and in Magoh siRNA treated melanoma cell lines. Together our findings indicate that Magoh-regulated proliferation of melanoblasts in the dermis may be critical for production of epidermally-bound melanoblasts. Our results point to a central role for Magoh in melanocyte development. PMID:23333945

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-01-01

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

  11. 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.

  12. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    Science.gov (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. PMID:27341758

  13. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    Science.gov (United States)

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells.

  14. Molecular Evolution of the Neural Crest Regulatory Network in Ray-Finned Fish.

    Science.gov (United States)

    Kratochwil, Claudius F; Geissler, Laura; Irisarri, Iker; Meyer, Axel

    2015-11-01

    Gene regulatory networks (GRN) are central to developmental processes. They are composed of transcription factors and signaling molecules orchestrating gene expression modules that tightly regulate the development of organisms. The neural crest (NC) is a multipotent cell population that is considered a key innovation of vertebrates. Its derivatives contribute to shaping the astounding morphological diversity of jaws, teeth, head skeleton, or pigmentation. Here, we study the molecular evolution of the NC GRN by analyzing patterns of molecular divergence for a total of 36 genes in 16 species of bony fishes. Analyses of nonsynonymous to synonymous substitution rate ratios (dN/dS) support patterns of variable selective pressures among genes deployed at different stages of NC development, consistent with the developmental hourglass model. Model-based clustering techniques of sequence features support the notion of extreme conservation of NC-genes across the entire network. Our data show that most genes are under strong purifying selection that is maintained throughout ray-finned fish evolution. Late NC development genes reveal a pattern of increased constraints in more recent lineages. Additionally, seven of the NC-genes showed signs of relaxation of purifying selection in the famously species-rich lineage of cichlid fishes. This suggests that NC genes might have played a role in the adaptive radiation of cichlids by granting flexibility in the development of NC-derived traits-suggesting an important role for NC network architecture during the diversification in vertebrates. PMID:26475317

  15. Regulation of pre-otic brain development by the cephalic neural crest.

    Science.gov (United States)

    Creuzet, Sophie E

    2009-09-15

    Emergence of the neural crest (NC) is considered an essential asset in the evolution of the chordate phylum, as specific vertebrate traits such as peripheral nervous system, cephalic skeletal tissues, and head development are linked to the NC and its derivatives. It has been proposed that the emergence of the NC was responsible for the formation of a "new head" characterized by the spectacular development of the forebrain and associated sense organs. It was previously shown that removal of the cephalic NC (CNC) prevents the formation of the facial structures but also results in anencephaly. This article reports on the molecular mechanisms whereby the CNC controls cephalic neurulation and brain morphogenesis. This study demonstrates that molecular variations of Gremlin and Noggin level in CNC account for morphological changes in brain size and development. CNC cells act in these processes through a multi-step control and exert cumulative effects counteracting bone morphogenetic protein signaling produced by the neighboring tissues (e.g., adjacent neuroepithelium, ventro-medial mesoderm, superficial ectoderm). These data provide an explanation for the fact that acquisition of the NC during the protochordate-to-vertebrate transition has coincided with a large increase of brain vesicles. PMID:19720987

  16. 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. PMID:27266404

  17. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Science.gov (United States)

    Zhang, Jie Ting; Weng, Zhi Hui; Tsang, Kam Sze; Tsang, Lai Ling; Chan, Hsiao Chang; Jiang, Xiao Hua

    2016-01-01

    The biologic studies of human neural crest stem cells (hNCSCs) are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs). For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

  18. MycN Is Critical for the Maintenance of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells.

    Directory of Open Access Journals (Sweden)

    Jie Ting Zhang

    Full Text Available The biologic studies of human neural crest stem cells (hNCSCs are extremely challenging due to the limited source of hNCSCs as well as ethical and technical issues surrounding isolation of early human embryonic tissues. On the other hand, vast majority of studies on MycN have been conducted in human tumor cells, thus, the role of MycN in normal human neural crest development is completely unknown. In the present study, we determined the role of MycN in hNCSCs isolated from in vitro-differentiating human embryonic stem cells (hESCs. For the first time, we show that suppression of MycN in hNCSCs inhibits cell growth and cell cycle progression. Knockdown of MycN in hNCSCs increases the expression of Cdkn1a, Cdkn2a and Cdkn2b, which encodes the cyclin-dependent kinases p21CIP1, p16 INK4a and p15INK4b. In addition, MycN is involved in the regulation of human sympathetic neurogenesis, as knockdown of MycN enhances the expression of key transcription factors involved in sympathetic neuron differentiation, including Phox2a, Phox2b, Mash1, Hand2 and Gata3. We propose that unlimited source of hNCSCs provides an invaluable platform for the studies of human neural crest development and diseases.

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

    Science.gov (United States)

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

    2016-03-15

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

  20. Sonic hedgehog is a chemotactic neural crest cell guide that is perturbed by ethanol exposure.

    Science.gov (United States)

    Tolosa, Ezequiel J; Fernández-Zapico, Martín E; Battiato, Natalia L; Rovasio, Roberto A

    2016-01-01

    Our aim was to understand the involvement of Sonic hedgehog (Shh) morphogen in the oriented distribution of neural crest cells (NCCs) toward the optic vesicle and to look for potential disorders of this guiding mechanism after ethanol exposure. In vitro directional analysis showed the chemotactic response of NCCs up Shh gradients and to notochord co-cultures (Shh source) or to their conditioned medium, a response inhibited by anti-Shh antibody, receptor inhibitor cyclopamine and anti-Smo morpholino (MO). Expression of the Ptch-Smo receptor complex on in vitro NCCs was also shown. In whole embryos, the expression of Shh mRNA and protein was seen in the ocular region, and of Ptch, Smo and Gli/Sufu system on cephalic NCCs. Anti-Smo MO or Ptch-mutated plasmid (Ptch1(Δloop2)) impaired cephalic NCC migration/distribution, with fewer cells invading the optic region and with higher cell density at the homolateral mesencephalic level. Beads embedded with cyclopamine (Smo-blocking) or Shh (ectopic signal) supported the role of Shh as an in vivo guide molecule for cephalic NCCs. Ethanol exposure perturbed in vitro and in vivo NCC migration. Early stage embryos treated with ethanol, in a model reproducing Fetal Alcohol Syndrome, showed later disruptions of craniofacial development associated with abnormal in situ expression of Shh morphogen. The results show the Shh/Ptch/Smo-dependent migration of NCCs toward the optic vesicle, with the support of specific inactivation with genetic and pharmacological tools. They also help to understand mechanisms of accurate distribution of embryonic cells and of their perturbation by a commonly consumed teratogen, and demonstrate, in addition to its other known developmental functions, a new biological activity of cellular guidance for Shh. PMID:26979762

  1. Specific diagnosis of neural crest tumours by MIBG scintigraphy; Diagnostic specifique des tumeurs issues de la crete neurale par la scintigraphie a la MIBG

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. [Het Nederlands Kanker Instituut, Amsterdam (Netherlands)

    1995-12-31

    MIBG scintigraphy has been used since 1981 as a diagnostic tool in pheochromocytoma and subsequently in a wide variety of neural crest tumors. The authors give the criteria for the choice between {sup 123}I and {sup 123}I-MIBG, remind drug interactions, report sensitivity and specificity values in main indications and discuss the relative merits of MIBG and pentetreotide scintigraphy. (author). 7 refs., 4 figs., 1 tab.

  2. Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics

    Directory of Open Access Journals (Sweden)

    JFW Greiner

    2011-12-01

    Full Text Available Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

  3. 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......, radiographs, dental casts, and medical records. PATIENTS: Ninety individuals (30 cleft lip, 30 cleft palate, and 30 combined cleft lip and palate), aged 5-27 years. MAIN OUTCOME MEASURES: Visual evaluation of tooth number and tooth morphology. RESULTS: Cleft lip: Dental deviations were predominantly observed...

  4. Delivery of Epidermal Neural Crest Stem Cells (EPI-NCSC) to hippocamp in Alzheimer's Disease Rat Model

    OpenAIRE

    Esmaeilzade, Banafshe; Nobakht, Maliheh; Joghataei, Mohammad Taghi; Rahbar Roshandel, Nahid; Rasouli, Homa; Samadi Kuchaksaraei, Ali; Hosseini, Seyed Mohammad; Najafzade, Nowruz; Asalgoo, Sara; Hejazian, Leila Beygom; Ghoroghi, Fatima Moghani

    2012-01-01

    Background: Alzheimer’s disease (AD) is characterized by progressive neuronal loss in hippocamp. Epidermal neural crest stem cells (EPI-NCSC) can differentiate into neurons, astrocytes and oligodendrocytes. The purpose of this study was to evaluate the effects of transplanting EPI-NCSC into AD rat model. Methods: Two weeks after induction of AD by injection of Amyloid-β 1-40 into CA1 area of rat hippocamp, Y-maze and single-trial passive avoidance tests were used to show deficit of learning a...

  5. Neural crest-mediated bone resorption is a determinant of species-specific jaw length.

    Science.gov (United States)

    Ealba, Erin L; Jheon, Andrew H; Hall, Jane; Curantz, Camille; Butcher, Kristin D; Schneider, Richard A

    2015-12-01

    Precise control of jaw length during development is crucial for proper form and function. Previously we have shown that in birds, neural crest mesenchyme (NCM) confers species-specific size and shape to the beak by regulating molecular and histological programs for the induction and deposition of cartilage and bone. Here we reveal that a hitherto unrecognized but similarly essential mechanism for establishing jaw length is the ability of NCM to mediate bone resorption. Osteoclasts are considered the predominant cells that resorb bone, although osteocytes have also been shown to participate in this process. In adults, bone resorption is tightly coupled to bone deposition as a means to maintain skeletal homeostasis. Yet, the role and regulation of bone resorption during growth of the embryonic skeleton have remained relatively unexplored. We compare jaw development in short-beaked quail versus long-billed duck and find that quail have substantially higher levels of enzymes expressed by bone-resorbing cells including tartrate-resistant acid phosphatase (TRAP), Matrix metalloproteinase 13 (Mmp13), and Mmp9. Then, we transplant NCM destined to form the jaw skeleton from quail to duck and generate chimeras in which osteocytes arise from quail donor NCM and osteoclasts come exclusively from the duck host. Chimeras develop quail-like jaw skeletons coincident with dramatically elevated expression of TRAP, Mmp13, and Mmp9. To test for a link between bone resorption and jaw length, we block resorption using a bisphosphonate, osteoprotegerin protein, or an MMP13 inhibitor, and this significantly lengthens the jaw. Conversely, activating resorption with RANKL protein shortens the jaw. Finally, we find that higher resorption in quail presages their relatively lower adult jaw bone mineral density (BMD) and that BMD is also NCM-mediated. Thus, our experiments suggest that NCM not only controls bone resorption by its own derivatives but also modulates the activity of mesoderm

  6. 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. PMID:27429770

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Ankita Das

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

  11. 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...

  12. In vitro and in vivo effects on neural crest stem cell differentiation by conditional activation of Runx1 short isoform and its effect on neuropathic pain behavior

    DEFF Research Database (Denmark)

    Kanaykina, Nadezda; Abelson, Klas; King, Dale;

    2010-01-01

    cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. We investigated whether conditional activation of Runx1 short isoform (Runx1a), which lacks a transcription activation domain, influences differentiation of neural crest stem cells (NCSCs) in vitro and in vivo...

  13. Portable Dynamic Positioning Control System on A Barge in Short-Crested Waves Using the Neural Network Algorithm

    Institute of Scientific and Technical Information of China (English)

    FANG Ming-chung; LEE Zi-yi

    2013-01-01

    This paper develops a nonlinear mathematical model to simulate the dynamic motion behavior of the barge equipped with the portable outboard Dynamic Positioning (DP) system in short-crested waves.The self-tuning Proportional-Derivative (PD) controller based on the neural network algorithm is applied to control the thrusters for optimal adjustment of the barge position in waves.In addition to the wave,the current,the wind and the nonlinear drift force are also considered in the calculations.The time domain simulations for the six-degree-of-freedom motions of the barge with the DP system are solved by the 4th order Runge-Kutta method which can compromise the efficiency and the accuracy of the simulations.The technique of the portable alternative DP system developed here can serve as a practical tool to assist those ships without being equipped with the DP facility while the dynamic positioning missions are needed.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Laura Jimenez

    2016-04-01

    Full Text Available 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, called Tg(snai1b:GFP, which labels epithelial cells undergoing EMT to produce sox10-positive neural crest (NC cells. Time-lapse and lineage analysis of Tg(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. Treating Tg(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 RA in vivo and raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells.

  16. Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function.

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    Kiran Ramgolam

    Full Text Available 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

  17. Disruption of the ERK/MAPK pathway in neural crest cells as a potential cause of Pierre Robin sequence.

    Science.gov (United States)

    Parada, Carolina; Han, Dong; Grimaldi, Alexandre; Sarrión, Patricia; Park, Shery S; Pelikan, Richard; Sanchez-Lara, Pedro A; Chai, Yang

    2015-11-01

    Disrupted ERK1/2 signaling is associated with several developmental syndromes in humans. To understand the function of ERK2 (MAPK1) in the postmigratory neural crest populating the craniofacial region, we studied two mouse models: Wnt1-Cre;Erk2(fl/fl) and Osr2-Cre;Erk2(fl/fl). Wnt1-Cre;Erk2(fl/fl) mice exhibited cleft palate, malformed tongue, micrognathia and mandibular asymmetry. Cleft palate in these mice was associated with delay/failure of palatal shelf elevation caused by tongue malposition and micrognathia. Osr2-Cre;Erk2(fl/fl) mice, in which the Erk2 deletion is restricted to the palatal mesenchyme, did not display cleft palate, suggesting that palatal clefting in Wnt1-Cre;Erk2(fl/fl) mice is a secondary defect. Tongues in Wnt1-Cre;Erk2(fl/fl) mice exhibited microglossia, malposition, disruption of the muscle patterning and compromised tendon development. The tongue phenotype was extensively rescued after culture in isolation, indicating that it might also be a secondary defect. The primary malformations in Wnt1-Cre;Erk2(fl/fl) mice, namely micrognathia and mandibular asymmetry, are linked to an early osteogenic differentiation defect. Collectively, our study demonstrates that mutation of Erk2 in neural crest derivatives phenocopies the human Pierre Robin sequence and highlights the interconnection of palate, tongue and mandible development. Because the ERK pathway serves as a crucial point of convergence for multiple signaling pathways, our study will facilitate a better understanding of the molecular regulatory mechanisms of craniofacial development.

  18. 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.

  19. Periconceptional folate consumption is associated with neonatal DNA methylation modifications in neural crest regulatory and cancer development genes.

    Science.gov (United States)

    Gonseth, Semira; Roy, Ritu; Houseman, E Andres; de Smith, Adam J; Zhou, Mi; Lee, Seung-Tae; Nusslé, Sébastien; Singer, Amanda W; Wrensch, Margaret R; Metayer, Catherine; Wiemels, Joseph L

    2015-01-01

    Folate deficiency during early embryonic development constitutes a risk factor for neural tube defects and potentially for childhood leukemia via unknown mechanisms. We tested whether folate consumption during the 12 months prior to conception induced DNA methylation modifications at birth in healthy neonates with a genome-wide and agnostic approach. We hypothesized that DNA methylation in genes involved in neural tube development and/or cancer susceptibility would be affected by folate exposure. We retrospectively assessed folate exposure at the time of conception by food-frequency questionnaires administered to the mothers of 343 healthy newborns. We measured genome-wide DNA methylation from neonatal blood spots. We implemented a method based on bootstrap resampling to decrease false-positive findings. Folate was inversely associated with DNA methylation throughout the genome. Among the top folate-associated genes that were replicated in an independent Gambian study were TFAP2A, a gene critical for neural crest development, STX11, a gene implicated in acute myeloid leukemia, and CYS1, a candidate gene for cystic kidney disease. Reduced periconceptional folate intake was associated with increased methylation and, in turn, decreased gene expression at these 3 loci. The top folate-sensitive genes defined by their associated CpG sites were enriched for numerous transcription factors by Gene Set Enrichment Analysis, including those implicated in cancer development (e.g., MYC-associated zinc finger protein). The influence of estimated periconceptional folate intake on neonatal DNA methylation levels provides potential mechanistic insights into the role of this vitamin in the development of neural tube defects and childhood cancers. PMID:26646725

  20. 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.

  1. Neural crest migration: interplay between chemorepellents, chemoattractants, contact inhibition, epithelial-mesenchymal transition, and collective cell migration.

    Science.gov (United States)

    Theveneau, Eric; Mayor, Roberto

    2012-01-01

    Neural crest (NC) cells are induced at the border of the neural plate and subsequently leave the neuroepithelium during a delamination phase. This delamination involves either a complete or partial epithelium-to-mesenchyme transition, which is directly followed by an extensive cell migration. During migration, NC cells are exposed to a wide variety of signals controlling their polarity and directionality, allowing them to colonize specific areas or preventing them from invading forbidden zones. For instance, NC cells are restricted to very precise pathways by the presence of inhibitory signals at the borders of each route, such as Semaphorins, Ephrins, and Slit/Robo. Although specific NC chemoattractants have been recently identified, there is evidence that repulsive interactions between the cells, in a process called contact inhibition of locomotion, is one of the major driving forces behind directional migration. Interestingly, in cellular and molecular terms, the invasive behavior of NC is similar to the invasion of cancer cells during metastasis. NC cells eventually settle in various places and make an immense contribution to the vertebrate body. They form the major constituents of the skull, the peripheral nervous system, and the pigment cells among others, which show the remarkable diversity and importance of this embryonic-stem cell like cell population. Consequently, several birth defects and craniofacial disorders, such as Treacher Collins syndrome, are due to improper NC cell migration. PMID:23801492

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

    Science.gov (United States)

    Willems, Bernd; Tao, Shijie; Yu, Tingsheng; Huysseune, Ann; Witten, Paul Eckhard; Winkler, Christoph

    2015-01-01

    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.

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

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    Ankush Gosain

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

  4. Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury

    OpenAIRE

    Neirinckx, Virginie; Agirman, Gulistan; Coste, Cécile; Marquet, Alice; Dion, Valérie; Rogister, Bernard; Franzen, Rachelle; Wislet, Sabine

    2015-01-01

    Introduction Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a...

  5. 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.

  6. Strict perpendicular orientation of neural crest-derived neurons in vitro is dependent on an extracellular gradient of voltage.

    Science.gov (United States)

    Pan, Linjie; Borgens, Richard Ben

    2012-07-01

    We report extraordinary perpendicular orientations of neurons dependent on the presence of an external direct current (DC) voltage gradient. We chose chick dorsal root and postganglionic sympathetic neurons to evaluate. These were cultured in observation chambers in which the cells were separated from electrode products or substrate effects and maintained at 35°C. Both types of neurons showed a rapid restructuring of their anatomy. Typically, neurites that were not perpendicular to the voltage gradient were quickly resorbed into the cell body within a few minutes. Over 3-6 hr, significant new neurite growth occurred and was patterned perpendicular to the DC electrical field (Ef). This preferred asymmetry was dependent on the Ef, as was the initial retrograde degeneration of fibers. At 400-500 mV/mm, over 90% of the cells in culture assumed this orientation. Removal of the DC Ef led to a loss of the preferred orientation, with further random growth within the chambers. This is the first report of such responses in dorsal root ganglion neurons. We also used sympathetic neurons as a meaningful comparison to analyze whether there were any qualitative or quantitative differences between these two cell types of neural crest origin. We discuss the means by which these orientations were achieved.

  7. 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.

  8. Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences.

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Alix, Philippe; Leprince, Pierre; Glejzer, Aneta; Poulet, Christophe; Hennuy, Benoit; Sommer, Lukas; Shakhova, Olga; Rogister, Bernard

    2012-08-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crest stem cells (NCSC) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSC), including their similarities and differences. In this paper, using transcriptomic as well as proteomic technologies, we compared NCSC to MSC and stromal nestin-positive cells, all of them isolated from adult bone marrow. We demonstrated that the nestin-positive cell population, which was the first to be described as able to differentiate into functional neurons, was a mixed population of NCSC and MSC. More interestingly, we demonstrated that MSC shared with NCSC the same ability to truly differentiate into Tuj1-positive cells when co-cultivated with paraformaldehyde-fixed cerebellar granule neurons. Altogether, those results suggest that both NCSC and MSC can be considered as important tools for cellular therapies in order to replace neurons in various neurological diseases. PMID:22349262

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

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    Philip C Wrage

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

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

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    Kawakami Minoru

    2011-11-01

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

  11. Biological properties of neural crest-derived multipotent stem cells from the bulge region of whisker follicle expanded in new culture conditions

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    Vasyliev R. G.

    2014-11-01

    Full Text Available Aim. The work is aimed at obtaining the culture of neural crest-derived multipotent stem cells (NC-MSCs in new culture conditions and to investigate their biological properties. Methods. NC-MSCs were grown from the explants of the bulge region of whisker follicle of adult mice. The cell cultures were examined by the following methods: sphere-forming assay, directed multilineage differentiation, CFU assay, immunocytochemistry, flow cytometry, RT-PCR. Results. The obtained NC-MSCs expressed the typical neural crest markers (nestin, Sox10 and Sox2 and were differentiated into adipocytes, osteoblasts and Schwann cells. Under our original growing conditions, the culture of NC-MSCs at the third passage had the following parameters: 66.8 % nestin+, 3.1 % ALDH brigth and 33.3 % clonogenic cells. The NC-MSCs growth rate depended on plating density. EGF and bFGF demonstrated a dose-dependent mitogenic action on NC-MSCs. Conclusions. The proposed approach permits the NC-MSC expansion with the maintenance of their main functional properties. Further optimization of the culture conditions will be based on the use of growth factors and low plating density.

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

    International Nuclear Information System (INIS)

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

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-10

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

  15. Crested caracara

    Science.gov (United States)

    Ellis, D.H.; Smith, D.G.; Whaley, W.H.; Ellis, C.H.; Glinski, Richard L.; Pendleton, Beth Giron; Moss, Mary Beth; LeFranc, Maurice N.=; Millsap, Brian A.; Hoffman, Stephen W.

    1988-01-01

    The crested caracara's range extends from the southern United States south to Tierra del Fuego. Although the caracara has been recorded in all of the southwestern states, it occurs regularly only in southern Arizona and central, southern and coastal Texas. Its distribution is closely linked to the availability of carrion. Throughout its range, thecaracara is associated with open habitats such as desertscrub, grassland and savanna. Nesting pairs usually produce one brood each breeding season, which extends from December through August. Eggs are laid from March into early June and clutch size averages two to three eggs. Young fledge in June and July and may remain with the adults for several weeks. Management recommendations for the crested caracara include clarifying its status in the Southwest. using supplemental feeding and modifying habitats to encourage recolonization of previously occupied areas and movement into new areas.

  16. 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

  17. CREST Syndrome

    OpenAIRE

    Tuğçe Köksüz; Zeynep Nurhan Saraçoğlu; Ayşe Esra Koku-Aksu; İlham Sabuncu; Cengiz Korkmaz

    2014-01-01

    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 ...

  18. The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest

    Science.gov (United States)

    Escriva, Hector; Holland, Nicholas D.; Gronemeyer, Hinrich; Laudet, Vincent; Holland, Linda Z.

    2002-01-01

    Amphioxus, the closest living invertebrate relative of the vertebrates, has a notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form, AmphiPax1, which is normally downregulated where gill slits form, remains upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To dissect the role of RA signaling in patterning chordate embryos, we have cloned the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR-AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or IR7 retinoic acid response elements (RAREs). The 5' untranslated region of AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation. The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle (homologous to the diencephalon plus anterior midbrain), while AmphiRAR expression is high in the equivalent of the hindbrain and spinal cord. Similarly, while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds of the endoderm, the highest AmphiRAR expression is in the middle third. Expression of AmphiRAR is upregulated by exogenous RA and completely downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx posteriorly; the first three gill slit primordia are elongated and shifted posteriorly, but do not penetrate, and additional, non-penetrating gill slit primordia are induced. Thus, in an organism without neural crest, initiation and penetration of gill slits appear to be separate events mediated by distinct levels of RA signaling in the pharyngeal endoderm. Although these compounds have little effect on levels of AmphiTR2/4 expression, RA

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

    Science.gov (United States)

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

    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(+) cells decreased whilst the percentage of GFAP(+) cells increased with age. The results demonstrated that alterations in ENCC growth characteristics occur with increased culture time, which may partially account for the poor results of proposed cell therapies. PMID:27068376

  20. 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.

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

    Science.gov (United States)

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

    2015-10-01

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

  2. Requirement for frzb and fzd7a in cranial neural crest convergence and extension mechanisms during zebrafish palate and jaw morphogenesis.

    Science.gov (United States)

    Kamel, George; Hoyos, Tatiana; Rochard, Lucie; Dougherty, Max; Kong, Yawei; Tse, William; Shubinets, Valeriy; Grimaldi, Michael; Liao, Eric C

    2013-09-15

    Regulation of convergence and extension by wnt-frizzled signaling is a common theme in embryogenesis. This study examines the functional requirements of frzb and fzd7a in convergence and extension mechanisms during craniofacial development. Using a morpholino knockdown approach, we found that frzb and fzd7a are dispensable for directed migration of the bilateral trabeculae, but necessary for the convergence and extension of the palatal elements, where the extension process is mediated by chondrocyte proliferation, morphologic change and intercalation. In contrast, frzb and fzd7a are required for convergence of the mandibular prominences, where knockdown of either frzb or fzd7a resulted in complete loss of lower jaw structures. Further, we found that bapx1 was specifically downregulated in the wnt9a/frzb/fzd7a morphants, while general neural crest markers were unaffected. In addition, expression of wnt9a and frzb was also absent in the edn-/- mutant. Notably, over-expression of bapx1 was sufficient to partially rescue mandibular elements in the wnt9a/frzb/fzd7a morphants, demonstrating genetic epistasis of bapx1 acting downstream of edn1 and wnt9a/frzb/fzd7a in lower jaw development. This study underscores the important role of wnt-frizzled signaling in convergence and extension in palate and craniofacial morphogenesis, distinct regulation of upper vs. lower jaw structures, and integration of wnt-frizzled with endothelin signaling to coordinate shaping of the facial form.

  3. Retinoic acid upregulates ret and induces chain migration and population expansion in vagal neural crest cells to colonise the embryonic gut.

    Directory of Open Access Journals (Sweden)

    Johanna E Simkin

    Full Text Available Vagal neural crest cells (VNCCs arise in the hindbrain, and at (avian embryonic day (E 1.5 commence migration through paraxial tissues to reach the foregut as chains of cells 1-2 days later. They then colonise the rest of the gut in a rostrocaudal wave. The chains of migrating cells later resolve into the ganglia of the enteric nervous system. In organ culture, E4.5 VNCCs resident in the gut (termed enteric or ENCC which have previously encountered vagal paraxial tissues, rapidly colonised aneural gut tissue in large numbers as chains of cells. Within the same timeframe, E1.5 VNCCs not previously exposed to paraxial tissues provided very few cells that entered the gut mesenchyme, and these never formed chains, despite their ability to migrate in paraxial tissue and in conventional cell culture. Exposing VNCCs in vitro to paraxial tissue normally encountered en route to the foregut conferred enteric migratory ability. VNCC after passage through paraxial tissue developed elements of retinoic acid signalling such as Retinoic Acid Binding Protein 1 expression. The paraxial tissue's ability to promote gut colonisation was reproduced by the addition of retinoic acid, or the synthetic retinoid Am80, to VNCCs (but not to trunk NCCs in organ culture. The retinoic acid receptor antagonist CD 2665 strongly reduced enteric colonisation by E1.5 VNCC and E4.5 ENCCs, at a concentration suggesting RARα signalling. By FACS analysis, retinoic acid application to vagal neural tube and NCCs in vitro upregulated Ret; a Glial-derived-neurotrophic-factor receptor expressed by ENCCs which is necessary for normal enteric colonisation. This shows that early VNCC, although migratory, are incapable of migrating in appropriate chains in gut mesenchyme, but can be primed for this by retinoic acid. This is the first instance of the characteristic form of NCC migration, chain migration, being attributed to the application of a morphogen.

  4. NEURAL AND CARDIAC TOXICITIES ASSOCIATED WITH 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA)

    OpenAIRE

    Baumann, Michael H.; Rothman, Richard B.

    2009-01-01

    (±)-3,4-Methylenedioxymethamphetamine (MDMA) is a commonly abused illicit drug which affects multiple organ systems. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been viewed as neurotoxicity. Recent data implicate MDMA in the development of valvular heart disease (VHD). The present paper reviews several issues related to MDMA-associated neural and cardiac toxicities. The hypothesis of MDMA neurotoxicit...

  5. 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.

  6. Transient Global Amnesia following Neural and Cardiac Angiography May Be Related to Ischemia

    Directory of Open Access Journals (Sweden)

    Hongzhou Duan

    2016-01-01

    Full Text Available Introduction. Transient global amnesia (TGA following angiography is rare, and the pathogenesis has not been illustrated clearly till now. The aim of this research is to explore the pathogenesis of TGA following angiography by analyzing our data and reviewing the literature. Methods. We retrospectively studied 20836 cases with angiography in our hospital between 2007 and 2015 and found 9 cases with TGA following angiography. The data of these 9 cases were analyzed. Results. We found all 9 cases with TGA following neural angiography (5 in 4360 or cardiac angiography (4 in 8817 and no case with TGA following peripheral angiography (0 in 7659. Statistical difference was found when comparing the neural and cardiac angiography group with peripheral group (p=0.022. Two cases with TGA were confirmed with small acute infarctions in hippocampus after angiography. This might be related to the microemboli which were rushed into vertebral artery following blood flow during neural angiography or cardiac angiography. There was no statistical difference when comparing the different approaches for angiography (p=0.82 and different contrast agents (p=0.619. Conclusion. Based on the positive findings of imaging study and our analysis, we speculate that ischemia in the medial temporal lobe with the involvement of the hippocampus might be an important reason of TGA following angiography.

  7. Automated Cardiac Beat Classification Using RBF Neural Networks

    Directory of Open Access Journals (Sweden)

    Ali Khazaee

    2013-04-01

    Full Text Available This paper proposes a four stage, denoising, feature extraction, optimization and classification method for detection of premature ventricular contractions. In the first stage, we investigate the application of wavelet denoising in noise reduction of multi-channel high resolution ECG signals. In this stage, the Stationary Wavelet Transform is used. Feature extraction module extracts ten ECG morphological features and one timing interval feature. Then a number of radial basis function (RBF neural networks with different value of spread parameter are designed and compared their ability for classification of three different classes of ECG signals. Genetic Algorithm is used to find best value of RBF parameters. A classification accuracy of 100% for training dataset and 95.66% for testing dataset and an overall accuracy of detection of 95.83% were achieved over seven files from the MIT/BIH arrhythmia database.

  8. Control of the collective migration of enteric neural crest cells by the Complement anaphylatoxin C3a and N-cadherin.

    Science.gov (United States)

    Broders-Bondon, Florence; Paul-Gilloteaux, Perrine; Gazquez, Elodie; Heysch, Julie; Piel, Matthieu; Mayor, Roberto; Lambris, John D; Dufour, Sylvie

    2016-06-01

    We analyzed the cellular and molecular mechanisms governing the adhesive and migratory behavior of enteric neural crest cells (ENCCs) during their collective migration within the developing mouse gut. We aimed to decipher the role of the complement anaphylatoxin C3a during this process, because this well-known immune system attractant has been implicated in cephalic NCC co-attraction, a process controlling directional migration. We used the conditional Ht-PA-cre transgenic mouse model allowing a specific ablation of the N-cadherin gene and the expression of a fluorescent reporter in migratory ENCCs without affecting the central nervous system. We performed time-lapse videomicroscopy of ENCCs from control and N-cadherin mutant gut explants cultured on fibronectin (FN) and micropatterned FN-stripes with C3a or C3aR antagonist, and studied cell migration behavior with the use of triangulation analysis to quantify cell dispersion. We performed ex vivo gut cultures with or without C3aR antagonist to determine the effect on ENCC behavior. Confocal microscopy was used to analyze the cell-matrix adhesion properties. We provide the first demonstration of the localization of the complement anaphylatoxin C3a and its receptor on ENCCs during their migration in the embryonic gut. C3aR receptor inhibition alters ENCC adhesion and migration, perturbing directionality and increasing cell dispersion both in vitro and ex vivo. N-cadherin-null ENCCs do not respond to C3a co-attraction. These findings indicate that C3a regulates cell migration in a N-cadherin-dependent process. Our results shed light on the role of C3a in regulating collective and directional cell migration, and in ganglia network organization during enteric nervous system ontogenesis. The detection of an immune system chemokine in ENCCs during ENS development may also shed light on new mechanisms for gastrointestinal disorders. PMID:27041467

  9. 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.

  10. Control of the collective migration of enteric neural crest cells by the Complement anaphylatoxin C3a and N-cadherin.

    Science.gov (United States)

    Broders-Bondon, Florence; Paul-Gilloteaux, Perrine; Gazquez, Elodie; Heysch, Julie; Piel, Matthieu; Mayor, Roberto; Lambris, John D; Dufour, Sylvie

    2016-06-01

    We analyzed the cellular and molecular mechanisms governing the adhesive and migratory behavior of enteric neural crest cells (ENCCs) during their collective migration within the developing mouse gut. We aimed to decipher the role of the complement anaphylatoxin C3a during this process, because this well-known immune system attractant has been implicated in cephalic NCC co-attraction, a process controlling directional migration. We used the conditional Ht-PA-cre transgenic mouse model allowing a specific ablation of the N-cadherin gene and the expression of a fluorescent reporter in migratory ENCCs without affecting the central nervous system. We performed time-lapse videomicroscopy of ENCCs from control and N-cadherin mutant gut explants cultured on fibronectin (FN) and micropatterned FN-stripes with C3a or C3aR antagonist, and studied cell migration behavior with the use of triangulation analysis to quantify cell dispersion. We performed ex vivo gut cultures with or without C3aR antagonist to determine the effect on ENCC behavior. Confocal microscopy was used to analyze the cell-matrix adhesion properties. We provide the first demonstration of the localization of the complement anaphylatoxin C3a and its receptor on ENCCs during their migration in the embryonic gut. C3aR receptor inhibition alters ENCC adhesion and migration, perturbing directionality and increasing cell dispersion both in vitro and ex vivo. N-cadherin-null ENCCs do not respond to C3a co-attraction. These findings indicate that C3a regulates cell migration in a N-cadherin-dependent process. Our results shed light on the role of C3a in regulating collective and directional cell migration, and in ganglia network organization during enteric nervous system ontogenesis. The detection of an immune system chemokine in ENCCs during ENS development may also shed light on new mechanisms for gastrointestinal disorders.

  11. Lack of organ specific commitment of vagal neural crest cell derivatives as shown by back-transplantation of GFP chicken tissues.

    Science.gov (United States)

    Freem, Lucy J; Delalande, Jean Marie; Campbell, Alison M; Thapar, Nikhil; Burns, Alan J

    2012-01-01

    Neural crest cells (NCC) are multipotent progenitors that migrate extensively throughout the developing embryo and generate a diverse range of cell types. Vagal NCC migrate from the hindbrain into the foregut and from there along the gastrointestinal tract to form the enteric nervous system (ENS), the intrinsic innervation of the gut, and into the developing lung buds to form the intrinsic innervation of the lungs. The aim of this study was to determine the developmental potential of vagal NCC that had already colonised the gut or the lungs. We used transgenic chicken embryos that ubiquitously express green fluorescent protein (GFP) to permanently mark and fate-map vagal NCC using intraspecies grafting. This was combined with back-transplantation of gut and lung segments, containing GFP-positive NCC, into the vagal region of a second recipient embryo to determine, using immunohistochemical staining, whether gut or lung NCC are competent of re-colonising both these organs, or whether their fate is restricted. Chick(GFP)-chick intraspecies grafting efficiently labelled NCC within the gut and lung of chick embryos. When segments of embryonic day (E)5.5 pre-umbilical midgut containing GFP-positive NCC were back-transplanted into the vagal region of E1.5 host embryos, the GFP-positive NCC remigrated to colonise both the gut and lungs and differentiated into neurons in stereotypical locations. However, GFP-positive lung NCC did not remigrate when back-transplanted. Our studies suggest that gut NCC are not restricted to colonising only this organ, since upon back-transplantation GFP-positive gut NCC colonised both the gut and the lung.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

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

    2010-11-15

    Abnormalities in the development of enteric neural crest-derived progenitors (ENPs) that generate the enteric nervous system (ENS) can lead to aganglionosis in a variable portion of the distal gastrointestinal tract. Cumulative evidence suggests that variation of aganglionosis is due to gene interactions that modulate the ability of ENPs to populate the intestine; however, the developmental processes underlying this effect are unknown. We hypothesized that differences in enteric ganglion deficits could be attributable to the effects of genetic background on early developmental processes, including migration, proliferation, or lineage divergence. Developmental processes were investigated in congenic Sox10(Dom) mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B6) and C3HeB/FeJ (C3Fe). Immuno-staining on whole-mount fetal gut tissue and dissociated cell suspensions was used to assess migration and proliferation. Flow cytometry utilizing the cell surface markers p75 and HNK-1 was used to isolate live ENPs for analysis of developmental potential. Frequency of ENPs was reduced in Sox10(Dom) embryos relative to wild-type embryos, but was unaffected by genetic background. Both migration and developmental potential of ENPs in Sox10(Dom) embryos were altered by inbred strain background with the most highly significant differences seen for developmental potential between strains and genotypes. In vivo imaging of fetal ENPs and postnatal ganglia demonstrates that altered lineage divergence impacts ganglia in the proximal intestine. Our analysis demonstrates that genetic background alters early ENS development and suggests that abnormalities in lineage diversification can shift the proportions of ENP populations and thus may contribute to ENS deficiencies in vivo.

  14. Macro-micro imaging of cardiac-neural circuits in co-cultures from normal and diseased hearts.

    Science.gov (United States)

    Bub, Gil; Burton, Rebecca-Ann B

    2015-07-15

    The autonomic nervous system plays an important role in the modulation of normal cardiac rhythm, but is also implicated in modulating the heart's susceptibility to re-entrant ventricular and atrial arrhythmias. The mechanisms by which the autonomic nervous system is pro-arrhythmic or anti-arrhythmic is multifaceted and varies for different types of arrhythmia and their cardiac substrates. Despite decades of research in this area, fundamental questions related to how neuron density and spatial organization modulate cardiac wave dynamics remain unanswered. These questions may be ill-posed in intact tissues where the activity of individual cells is often experimentally inaccessible. Development of simplified biological models that would allow us to better understand the influence of neural activation on cardiac activity can be beneficial. This Symposium Review summarizes the development of in vitro cardiomyocyte cell culture models of re-entrant activity, as well as challenges associated with extending these models to include the effects of neural activation.

  15. Optogenetic stimulation of multiwell MEA plates for neural and cardiac applications

    Science.gov (United States)

    Clements, Isaac P.; Millard, Daniel C.; Nicolini, Anthony M.; Preyer, Amanda J.; Grier, Robert; Heckerling, Andrew; Blum, Richard A.; Tyler, Phillip; McSweeney, K. M.; Lu, Yi-Fan; Hall, Diana; Ross, James D.

    2016-03-01

    Microelectrode array (MEA) technology enables advanced drug screening and "disease-in-a-dish" modeling by measuring the electrical activity of cultured networks of neural or cardiac cells. Recent developments in human stem cell technologies, advancements in genetic models, and regulatory initiatives for drug screening have increased the demand for MEA-based assays. In response, Axion Biosystems previously developed a multiwell MEA platform, providing up to 96 MEA culture wells arrayed into a standard microplate format. Multiwell MEA-based assays would be further enhanced by optogenetic stimulation, which enables selective excitation and inhibition of targeted cell types. This capability for selective control over cell culture states would allow finer pacing and probing of cell networks for more reliable and complete characterization of complex network dynamics. Here we describe a system for independent optogenetic stimulation of each well of a 48-well MEA plate. The system enables finely graded control of light delivery during simultaneous recording of network activity in each well. Using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes and rodent primary neuronal cultures, we demonstrate high channel-count light-based excitation and suppression in several proof-of-concept experimental models. Our findings demonstrate advantages of combining multiwell optical stimulation and MEA recording for applications including cardiac safety screening, neural toxicity assessment, and advanced characterization of complex neuronal diseases.

  16. Detection and classification of cardiac ischemia using vectorcardiogram signal via neural network

    Directory of Open Access Journals (Sweden)

    Ali Reza Mehri Dehnavi

    2011-01-01

    Full Text Available Background: Various techniques are used in diagnosing cardiac diseases. The electrocardiogram is one of these tools in common use. In this study vectorcardiogram (VCG signals are used as a tool for detection of cardiac ischemia. Methods: VCG signals used in this study were obtained form 60 patients suspected to have ischemia disease and 10 normal candidates. Verification of the ischemia had done by the cardiologist during strain test by the evaluation of electrocardiogram (ECG records and patient′s clinical history. The recorder device was Cardiax digital recorder system. The VCG signals were recorded in Frank lead configuration system. Results: Extracted ischemia VCG signals have been configured with 22 features. Feature dimensionalities were reduced by the use of Independent Components Analysis and Principal Component Analysis tools. Results obtained from strain test indicated that among 60 subjects, 50 had negative results and 10 had positive results. Ischemia detection of neural network using VCG parameters indicates 86% accuracy. Classification result on neural network using ECG ischemia detection parameters is 73% accurate. Accumulative evaluation including VCG analysis and strain test indicates 90% consistency. Conclusions: Regarding the obtained results in this study, VCG has higher accuracy than ECG, so that in cases which ECG signal cannot provide certain diagnosis of existence or non-existence of ischemia, VCG signal can help in a wider range. We suggest the use of VCG as an auxiliary low cost tool in ischemia detection.

  17. Retinol dehydrogenase, RDH1l, is essential for the heart development and cardiac performance in zebrafish

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; ZHANG Li-feng; GUI Yong-hao; SONG Hou-yan

    2013-01-01

    Background Retinoic acid (RA) is a potent signaling molecule that plays pleiotropic roles in patterning,morphogenesis,and organogenesis during embryonic development.The synthesis from retinol (vitamin A) to retinoic acid requires two sequential oxidative steps.The first step involves the oxidation of retinol to retinal through the action of retinol dehydrogenases.Retinol dehydrogenases1l (RDH1l) is a novel zebrafish retinol dehydrogenase.Herein we investigated the role of zebrafish RDH1l in heart development and cardiac performance in detail.Methods RDH1l specific morpholino was used to reduce the function of RDH1l in zebrafish.The gene expressions were observed by using whole mount in situ hybridization.Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf).The cardiac performance was analyzed by measuring ventricular shortening fraction (VSF).Results The knock-down of RDH1l led to abnormal neural crest cells migration and reduced numbers of neural crest cells in RDH1l morphant embryos.The reduced numbers of cardiac neural crest cells also can be seen in RDH1l morphant embryos.Furthermore,the morpholino-mediated knock-down of RDH1l resulted in the abnormal heart loop.The left-right determining genes expression pattern was altered in RDH1l morphant embryos.The impaired cardiac performance was observed in RDH1l morphant embryos.Taken together,these data demonstrate that RDH1l is essential for the heart development and cardiac performance in zebrafish.Conclusions RDH1l plays a important role in the neural crest cells development,and then ultimately affects the heart loop and cardiac performance.These results show for the first time that an enzyme involved in the retinol to retinaldehyde conversion participate in the heart development and cardiac performance in zebrafish.

  18. The influence of different SPECT reconstruction algorithms on cardiac ischemia with the use artificial neural networks

    International Nuclear Information System (INIS)

    The aim of the study was the attempt to evaluate the influence of two different methods of cardiac perfusion SPECT reconstruction (FBP and ITW) on clinical efficacy in diagnosing the coronary artery disease as well as the cardiac ischemia detection in three areas of heart vascularized by main coronary arteries: LAD, LCX and RCA with the use of artificial neural networks (ANN). The study was performed retrospectively with the use of the diagnostic image records as well as clinical dataset of 43 patients. Myocardial perfusion stress/rest SPECT study and X-ray coronarography data were evaluated for each patient. The results of coronary angiography were considered the reference method. The cardiac SPECT data were reconstructed using the two different methods: filtered backprojection (FBP) and iterative Wallis method (ITW). The local perfusion deficits denominated in stress and rest study in three main vessel cardiac segments were the main input values for the ANN. The sensitivity of detection of coronary artery disease with the of ANN was 95% for both FBP and ITW reconstruction technique (p≥0.05). The sensitivity analysis of regional ischemia detection by ANN in areas LAD, LCX and RCA provided 97%, 65% and 64%, correspondingly for FDP method. With the use of ITW algorithm the sensitivity in the respective regions was: 65%, 55% and 60%. The difference in sensitivity of ANN ischemia detection for the LAD region was statistically significant for FDP versus ITW reconstruction algorithm (p=0.0007). No statistical discrepancy in sensitivity was stated in the other regions due to reconstruction technique (p≥0.005). The compared method of reconstruction of myocardial perfusion SPECT studies the do not influence the clinical efficacy in diagnosing the coronary disease with the use of ANN. In case of ANN application for local ischemia recognition results of the study indicate the FBP algorithm effective. (author)

  19. Effect of Tbxl knock-down on cardiac performance in zebrafish

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-feng; GUI Yong-hao; WANG Yue-xiang; JIANG Qiu; SONG Hou-yan

    2010-01-01

    Background Tbxl is the major candidate gene for DiGeorge syndrome (DGS). Similar to defects observed in DGS patients, the structures disrupted in Tbxl-/- animal models are derived from the neural crest cells during development. Although the morphological phenotypes of some Tbxl knock-down animal models have been well described, analysis of the cardiac performance is limited. Therefore, myocardial performance was explored in Tbxl morpholino injected zebrafish embryos. Methods To elucidate these issues, Tbxl specific morpholino was used to reduce the function of Tbxl in zebrafish. The differentiation of the myocardial cells was observed using whole mount in situ hybridization. Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf). The cardiac performance was analyzed by measuring ventricular shortening fraction and atrial shortening fraction.Results Tbxl morpholino injected embryos were characterized by defects in the pharyngeal arches, otic vesicle, aortic arches and thymus. In addition, Tbxl knock down reduced the amount of pharyngeal neural crest cells in zebrafish. Abnormal cardiac morphology was visible in nearly 20% of the Tbxl morpholino injected embryos. The hearts in these embryos did not loop or loop incompletely. Importantly, cardiac performance and heart rate were reduced in Tbxl morpholino injected embryos.Conclusions Tbxl might play an essential role in the development of pharyngeal neural crest cells in zebrafish. Cardiac performance is impaired by Tbxl knock down in zebrafish.

  20. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    Science.gov (United States)

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

  1. Dpysl2 (CRMP2) and Dpysl3 (CRMP4) phosphorylation by Cdk5 and DYRK2 is required for proper positioning of Rohon-Beard neurons and neural crest cells during neurulation in zebrafish.

    Science.gov (United States)

    Tanaka, Hideomi; Morimura, Rii; Ohshima, Toshio

    2012-10-15

    Dpysl2 (CRMP2) and Dpysl3 (CRMP4) are involved in neuronal polarity and axon elongation in cultured neurons. These proteins are expressed in various regions of the developing nervous system, but their roles in vivo are largely unknown. In dpysl2 and dpysl3 double morphants, Rohon-Beard (RB) primary sensory neurons that were originally located bilaterally along the midline shifted their position to a more medial location in the dorsal-most part of spinal cord. A similar phenotype was observed in the cdk5 and dyrk2 double morphants. Dpysl2 and Dpysl3 phosphorylation mimics recovered this phenotype. Cell transplantation analysis demonstrated that this ectopic RB cell positioning was non-cell autonomous and correlated with the abnormal position of neural crest cells (NCCs), which also occupied the dorsal-most part of the spinal cord during the neural rod formation stage. The cell position of other interneuron and motor neurons within the central nervous system was normal in these morphants. These results suggest that the phosphorylation of Dpysl2 and Dpysl3 by Cdk5 and DYRK2 is required for the proper positioning of RB neurons and NCCs during neurulation in zebrafish embryos.

  2. Using Mixture Structures of Neural Networks in Order to Detect Cardiac Arrhythmias Using Fusion of Temporal and Wavelet Features

    Directory of Open Access Journals (Sweden)

    syed mohammd Razavi

    2011-05-01

    Full Text Available In recent years the use of intelligent systems in science and engineering, especially in the diagnosis of disease, is increasingly growing. In this paper a smart way to diagnose heart disease (cardiac arrhythmias is presented. This method is based on a combination of structures using neural networks for classification of normal operation and four abnormal heart functions. In the combination of these structures, some neural networks as a mediator, and some of them have been used as a specialist. In the proposed method firstly for removing noise from ECG signal, preprocessing was performed. The various time features (including fifteen properties and wavelet features (includes fifteen feature are extracted from the noise free signal and given the large number of selected features, principal components analysis is used for feature reduction to eight features. The proposed structures of MLP neural networks and RBF neural networks are appropriately trained for classification of arrhythmias and their performance has been evaluated. The results of the implementation of the proposed method on MIT / BIH database show the better performance in the diagnosis of cardiac arrhythmias compared to previous approaches.

  3. 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.…

  4. Automatic coronary calcium scoring in cardiac CT angiography using convolutional neural networks

    NARCIS (Netherlands)

    Wolterink, Jelmer M.; Leiner, Tim; Viergever, Max A.; Isgum, I

    2015-01-01

    The amount of coronary artery calcification (CAC) is a strong and independent predictor of cardiovascular events. Non-contrast enhanced cardiac CT is considered a reference for quantification of CAC. Recently, it has been shown that CAC may be quantified in cardiac CT angiography (CCTA). We present

  5. Chronic vagal stimulation for the treatment of low ejection fraction heart failure : results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    NARCIS (Netherlands)

    Zannad, Faiez; De Ferrari, Gaetano M; Tuinenburg, Anton E; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis; Castel, Maria Angeles; D'Onofrio, Antonio; Solomon, Scott D; Wold, Nicholas; Ruble, Stephen B

    2015-01-01

    AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure p

  6. Detection and classification of cardiac ischemia using vectorcardiogram signal via neural network

    OpenAIRE

    Ali Reza Mehri Dehnavi; Iman Farahabadi; Hossain Rabbani; Amin Farahabadi; Mohamad Parsa Mahjoob; Nasser Rajabi Dehnavi

    2011-01-01

    Background: Various techniques are used in diagnosing cardiac diseases. The electrocardiogram is one of these tools in common use. In this study vectorcardiogram (VCG) signals are used as a tool for detection of cardiac ischemia. Methods: VCG signals used in this study were obtained form 60 patients suspected to have ischemia disease and 10 normal candidates. Verification of the ischemia had done by the cardiologist during strain test by the evaluation of electrocardiogram (ECG) records ...

  7. Cardiac Arrhythmias Classification Method Based on MUSIC, Morphological Descriptors, and Neural Network

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available An electrocardiogram (ECG beat classification scheme based on multiple signal classification (MUSIC algorithm, morphological descriptors, and neural networks is proposed for discriminating nine ECG beat types. These are normal, fusion of ventricular and normal, fusion of paced and normal, left bundle branch block, right bundle branch block, premature ventricular concentration, atrial premature contraction, paced beat, and ventricular flutter. ECG signal samples from MIT-BIH arrhythmia database are used to evaluate the scheme. MUSIC algorithm is used to calculate pseudospectrum of ECG signals. The low-frequency samples are picked to have the most valuable heartbeat information. These samples along with two morphological descriptors, which deliver the characteristics and features of all parts of the heart, form an input feature vector. This vector is used for the initial training of a classifier neural network. The neural network is designed to have nine sample outputs which constitute the nine beat types. Two neural network schemes, namely multilayered perceptron (MLP neural network and a probabilistic neural network (PNN, are employed. The experimental results achieved a promising accuracy of 99.03% for classifying the beat types using MLP neural network. In addition, our scheme recognizes NORMAL class with 100% accuracy and never misclassifies any other classes as NORMAL.

  8. Cardiac Arrhythmias Classification Method Based on MUSIC, Morphological Descriptors, and Neural Network

    Science.gov (United States)

    Naghsh-Nilchi, Ahmad R.; Kadkhodamohammadi, A. Rahim

    2009-12-01

    An electrocardiogram (ECG) beat classification scheme based on multiple signal classification (MUSIC) algorithm, morphological descriptors, and neural networks is proposed for discriminating nine ECG beat types. These are normal, fusion of ventricular and normal, fusion of paced and normal, left bundle branch block, right bundle branch block, premature ventricular concentration, atrial premature contraction, paced beat, and ventricular flutter. ECG signal samples from MIT-BIH arrhythmia database are used to evaluate the scheme. MUSIC algorithm is used to calculate pseudospectrum of ECG signals. The low-frequency samples are picked to have the most valuable heartbeat information. These samples along with two morphological descriptors, which deliver the characteristics and features of all parts of the heart, form an input feature vector. This vector is used for the initial training of a classifier neural network. The neural network is designed to have nine sample outputs which constitute the nine beat types. Two neural network schemes, namely multilayered perceptron (MLP) neural network and a probabilistic neural network (PNN), are employed. The experimental results achieved a promising accuracy of 99.03% for classifying the beat types using MLP neural network. In addition, our scheme recognizes NORMAL class with 100% accuracy and never misclassifies any other classes as NORMAL.

  9. An Unusual Cause of Cardiac Arrhythmias; Mediastinal Schwannoma

    Directory of Open Access Journals (Sweden)

    Serdar Ozkan

    2014-02-01

    Full Text Available Schwannomas are rare tumours, which originated from neural crest cells. Thoracic schwannomas are very rare and most commonly seen in posterior mediastinum. In a 39 year old female patient whose tumor story dated back to 4 years, a 14 cm extra parenchymal intrathoracic tumor was observed to put minimal pressure on the heart. The patient%u2019s arrhythmia, who had preoperative complaints of palpitations, was improved after tumor excision. Although schwannomas generally are asympthomatic masses, they can lead mass effect according to their localization. In this study, patient with thoracic schwannoma presented with cardiac arrhythmia which never reported in literature so far.

  10. 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

  11. Recurrent Fully Convolutional Neural Networks for Multi-slice MRI Cardiac Segmentation

    OpenAIRE

    Poudel, Rudra P K; Lamata, Pablo; Montana, Giovanni

    2016-01-01

    In cardiac magnetic resonance imaging, fully-automatic segmentation of the heart enables precise structural and functional measurements to be taken, e.g. from short-axis MR images of the left-ventricle. In this work we propose a recurrent fully-convolutional network (RFCN) that learns image representations from the full stack of 2D slices and has the ability to leverage inter-slice spatial dependences through internal memory units. RFCN combines anatomical detection and segmentation into a si...

  12. Percutaneous autonomic neural modulation: A novel technique to treat cardiac arrhythmia

    International Nuclear Information System (INIS)

    Ablation and anti-arrhythmic medications have shown promise but have been met with varying success and unwanted side effects such as myocardial injury, arrhythmias, and morbidity from invasive surgical intervention. The answer to improving efficacy of ablation may include modulation of the cardiac aspect of the autonomic nervous system. Our lab has developed a novel approach and device to navigate the oblique sinus and to use DC current and saline/alcohol irrigation to selectively stimulate and block the autonomic ganglia found on the epicardial side of the heart. This novel approach minimizes myocardial damage from thermal injury and provides a less invasive and targeted approach. For feasibility, proof-of-concept, and safety monitoring, we carried out canine studies to test this novel application. Our results suggest a safer and less invasive way of modulating arrhythmogenic substrate that may lead to improved treatment of AF in humans

  13. Percutaneous autonomic neural modulation: A novel technique to treat cardiac arrhythmia

    Energy Technology Data Exchange (ETDEWEB)

    DeSimone, Christopher V.; Madhavan, Malini [Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (United States); Venkatachalam, Kalpathi L. [Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Jacksonville, FL (United States); Knudson, Mark B. [Mayo Clinic, Rochester, MN (United States); EnteroMedics, EnteroMedics, St. Paul, MN (United States); Asirvatham, Samuel J., E-mail: asirvatham.samuel@mayo.edu [Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (United States); Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN (United States)

    2013-05-15

    Ablation and anti-arrhythmic medications have shown promise but have been met with varying success and unwanted side effects such as myocardial injury, arrhythmias, and morbidity from invasive surgical intervention. The answer to improving efficacy of ablation may include modulation of the cardiac aspect of the autonomic nervous system. Our lab has developed a novel approach and device to navigate the oblique sinus and to use DC current and saline/alcohol irrigation to selectively stimulate and block the autonomic ganglia found on the epicardial side of the heart. This novel approach minimizes myocardial damage from thermal injury and provides a less invasive and targeted approach. For feasibility, proof-of-concept, and safety monitoring, we carried out canine studies to test this novel application. Our results suggest a safer and less invasive way of modulating arrhythmogenic substrate that may lead to improved treatment of AF in humans.

  14. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    OpenAIRE

    Zannad, Faiez; De Ferrari, Gaetano M.; Tuinenburg, Anton E.; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M.; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis

    2014-01-01

    Aim The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. Methods: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or contro...

  15. MicroRNA-21 can promote the differentiation of neural crest stem cells from human follicle into Schwann cells%miR-21促进毛囊神经嵴干细胞分化为许旺细胞

    Institute of Scientific and Technical Information of China (English)

    王艳华; 刘浩; 辛红; 白晓雪; 刘学娟; 倪宇昕

    2014-01-01

    BACKGROUND:MicroRNAs are a class of non-coding single-stranded smal RNA molecules containing 18–25 nucleotides that can bind to the 3’UTR of the mRNA molecules and regulate the protein expression of target genes. Studies have shown that microRNAs could regulate Schwann cel differentiation, myelination maturation and growth of the peripheral nerve. OBJECTIVE: To observe the expression of miR-21 during the differentiation of neural crest stem cels from human folicle into Schwann cels. METHODS: Hair folicle stem cels were cultured and neural crest stem cels were separated from human hair folicles by flow cytometry. Then, the neural crest stem cels were induced to differentiate into Schwann cels. qRT-PCR was used to detect the expression of miR-21 in the process of induction. Neural crest stem cels from hair folicles were divided into control group, agomir-21 group, agomir-NC group, antagomir-21 group and antagomir-NC group. The control group was without intervention. Agomir-21 group was transfected with miR-21 agonist, whereas Antagomir-21 group was transfected with miR-21 antagonist. agomir-NC group and antagomir-NC group were respectively negative controls of agomir-21 group and antagomir-21 group. Finaly, the possible target of miR-21 was searched in database. RESULTS AND CONCLUSION: Neural crest stem cels were successfuly separated from human hair folicles using flow cytometry and induced to differentiate into Schwann cels. In the process of cel differentiation, miR-21 expression was upregulated gradualy. Transfection of miR-21 agonist could enhance the stem cel differentiation into Schwann cels, whereas transfection of miR-21 antagonist could weaken the differentiation capacity of stem cels. Furthermore, we found via database searching that SOX2 maybe a target of miR-21 and participate in the regulatory role of miR-21. This study suggested that hair folicle neural crest stem cels can be used as an important source of Schwann cels and miR-21 can promote the

  16. Numerical Simulation of 3-D Wave Crests

    Institute of Scientific and Technical Information of China (English)

    YU Dingyong; ZHANG Hanyuan

    2003-01-01

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

  17. Crested Ibis%朱鹮

    Institute of Scientific and Technical Information of China (English)

    丁长青

    2010-01-01

    @@ The Crested Ibis(Nipponia nippon,Plates Ⅰ and Ⅱ)(Ciconiiformes: Threskiomithidae)is a mediumsized wading bird,ranging in length from 57.5 to 84.0 cm,with a longish neck and legs,a red featherless face with a crested white head.Its most distinctive morphological character is the long,slender and decurved bill,perfectly adapted for probing in water and mud,or even in cracks on dry ground.The nonbreeding adult is white,with orange cinnamon tones in the tail and flight-feathers.The long bill is black with a red tip.Its red legs do not extend beyond the tail in flight(Hoyo et al.,1992).

  18. Lineage and morphogenetic analysis of the cardiac valves.

    Science.gov (United States)

    de Lange, Frederik J; Moorman, Antoon F M; Anderson, Robert H; Männer, Jörg; Soufan, Alexandre T; de Gier-de Vries, Corrie; Schneider, Michael D; Webb, Sandra; van den Hoff, Maurice J B; Christoffels, Vincent M

    2004-09-17

    We used a genetic lineage-labeling system to establish the material contributions of the progeny of 3 specific cell types to the cardiac valves. Thus, we labeled irreversibly the myocardial (alphaMHC-Cre+), endocardial (Tie2-Cre+), and neural crest (Wnt1-Cre+) cells during development and assessed their eventual contribution to the definitive valvar complexes. The leaflets and tendinous cords of the mitral and tricuspid valves, the atrioventricular fibrous continuity, and the leaflets of the outflow tract valves were all found to be generated from mesenchyme derived from the endocardium, with no substantial contribution from cells of the myocardial and neural crest lineages. Analysis of chicken-quail chimeras revealed absence of any substantial contribution from proepicardially derived cells. Molecular and morphogenetic analysis revealed several new aspects of atrioventricular valvar formation. Marked similarities are seen during the formation of the mural leaflets of the mitral and tricuspid valves. These leaflets form by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface rather than by delamination of lateral cushions from the ventricular myocardial wall. The myocardial layer is subsequently removed by the process of apoptosis. In contrast, the aortic leaflet of the mitral valve, the septal leaflet of the tricuspid valve, and the atrioventricular fibrous continuity between these valves develop from the mesenchyme of the inferior and superior atrioventricular cushions. The tricuspid septal leaflet then delaminates from the muscular ventricular septum late in development. PMID:15297379

  19. Classification of Atrial Septal Defect and Ventricular Septal Defect with Documented Hemodynamic Parameters via Cardiac Catheterization by Genetic Algorithms and Multi-Layered Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Mustafa Yıldız

    2012-08-01

    Full Text Available Introduction: We aimed to develop a classification method to discriminate ventricular septal defect and atrial septal defect by using severalhemodynamic parameters.Patients and Methods: Forty three patients (30 atrial septal defect, 13 ventricular septal defect; 26 female, 17 male with documentedhemodynamic parameters via cardiac catheterization are included to study. Such parameters as blood pressure values of different areas,gender, age and Qp/Qs ratios are used for classification. Parameters, we used in classification are determined by divergence analysismethod. Those parameters are; i pulmonary artery diastolic pressure, ii Qp/Qs ratio, iii right atrium pressure, iv age, v pulmonary arterysystolic pressure, vi left ventricular sistolic pressure, vii aorta mean pressure, viii left ventricular diastolic pressure, ix aorta diastolicpressure, x aorta systolic pressure. Those parameters detected from our study population, are uploaded to multi-layered artificial neuralnetwork and the network was trained by genetic algorithm.Results: Trained cluster consists of 14 factors (7 atrial septal defect and 7 ventricular septal defect. Overall success ratio is 79.2%, andwith a proper instruction of artificial neural network this ratio increases up to 89%.Conclusion: Parameters, belonging to artificial neural network, which are needed to be detected by the investigator in classical methods,can easily be detected with the help of genetic algorithms. During the instruction of artificial neural network by genetic algorithms, boththe topology of network and factors of network can be determined. During the test stage, elements, not included in instruction cluster, areassumed as in test cluster, and as a result of this study, we observed that multi-layered artificial neural network can be instructed properly,and neural network is a successful method for aimed classification.

  20. 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 recall

  1. 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 ...

  2. Whistler wave trapping in a density crest

    International Nuclear Information System (INIS)

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

  3. Optical coherence tomography. A new high-resolution imaging technology to study cardiac development in chick embryos

    DEFF Research Database (Denmark)

    Yelbuz, T.M.; Choma, M.A.; Thrane, L.;

    2002-01-01

    Background-Optical coherence tomography (OCT) is a depth-resolved, noninvasive, non-destructive imaging modality, the use of which has yet to be fully realized in developmental biology. Methods and Results-We visualized embryonic chick hearts at looping stages using an OCT system with a 22 mum...... axial and 27 mum lateral resolution and an acquisition rate of 4000 A-scans per second. Normal chick embryos from stages 14 to 22 and sham-operated and cardiac neural crest-ablated embryos from stages 15 and 18 were scanned by OCT. Three-dimensional data sets were acquired and processed to create...... volumetric reconstructions and short video clips. The OCT-scanned embryos (2 in each group) were photographed after histological sectioning in comparable planes to those visualized by OCT. The optical and histological results showing cardiovascular microstructures such as myocardium, the cardiac jelly, and...

  4. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages

    International Nuclear Information System (INIS)

    Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal β III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders

  5. 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...

  6. 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....

  7. Combining Amplitude Spectrum Area with Previous Shock Information Using Neural Networks Improves Prediction Performance of Defibrillation Outcome for Subsequent Shocks in Out-Of-Hospital Cardiac Arrest Patients.

    Directory of Open Access Journals (Sweden)

    Mi He

    Full Text Available Quantitative ventricular fibrillation (VF waveform analysis is a potentially powerful tool to optimize defibrillation. However, whether combining VF features with additional attributes that related to the previous shock could enhance the prediction performance for subsequent shocks is still uncertain.A total of 528 defibrillation shocks from 199 patients experienced out-of-hospital cardiac arrest were analyzed in this study. VF waveform was quantified using amplitude spectrum area (AMSA from defibrillator's ECG recordings prior to each shock. Combinations of AMSA with previous shock index (PSI or/and change of AMSA (ΔAMSA between successive shocks were exercised through a training dataset including 255shocks from 99patientswith neural networks. Performance of the combination methods were compared with AMSA based single feature prediction by area under receiver operating characteristic curve(AUC, sensitivity, positive predictive value (PPV, negative predictive value (NPV and prediction accuracy (PA through a validation dataset that was consisted of 273 shocks from 100patients.A total of61 (61.0% patients required subsequent shocks (N = 173 in the validation dataset. Combining AMSA with PSI and ΔAMSA obtained highest AUC (0.904 vs. 0.819, p<0.001 among different combination approaches for subsequent shocks. Sensitivity (76.5% vs. 35.3%, p<0.001, NPV (90.2% vs. 76.9%, p = 0.007 and PA (86.1% vs. 74.0%, p = 0.005were greatly improved compared with AMSA based single feature prediction with a threshold of 90% specificity.In this retrospective study, combining AMSA with previous shock information using neural networks greatly improves prediction performance of defibrillation outcome for subsequent shocks.

  8. Effects of Serial Passage on the Characteristics and Cardiac and Neural Differentiation of Human Umbilical Cord Wharton’s Jelly-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Jianchun Lian

    2016-01-01

    Full Text Available Background and Objective. It is important to guarantee the quality of stem cells. Serial passage is the main approach to expand stem cells. This study evaluated effects of serial passage on the biological characteristics of human umbilical cord Wharton’s jelly-derived MSCs (WJ MSCs. Methods. Biological properties of WJ MSCs in the early (less than 10 passages, P10, middle (P11–20, and late (more than P20 phases including cell proliferation, cell cycle, phenotype, senescence, oncogene expression, stemness marker expression, and differentiation capacity were evaluated using flow cytometry, real-time PCR, immunocytofluorescence, and western blot. Results. It was found that there were no significant differences in cell proliferation, cell cycle, phenotype, and stemness marker expression in different phases. However, the expression of senescence-related gene, p21, and oncogene, c-Myc, was significantly upregulated in the late phase, which had close relations with the obviously increased cell senescence. Moreover, cardiac differentiation capability of WJ MSCs decreased whereas the propensity for neural differentiation increased significantly in the middle phase. Conclusions. This study reveals that WJ MSCs in the early and middle phases are relatively stable, and effect of serial passage on the lineage-specific differentiation should be considered carefully.

  9. Generalized crested products of Markov chains

    CERN Document Server

    D'Angeli, Daniele

    2010-01-01

    We define a finite Markov chain, called generalized crested product, which naturally appears as a generalization of the first crested product of Markov chains. A complete spectral analysis is developed and the $k$-step transition probability is given. It is important to remark that this Markov chain describes a more general version of the classical Ehrenfest diffusion model. As a particular case, one gets a generalization of the classical Insect Markov chain defined on the ultrametric space. Finally, an interpretation in terms of representation group theory is given, by showing the correspondence between the spectral decomposition of the generalized crested product and the Gelfand pairs associated with the generalized wreath product of permutation groups.

  10. Sensitivity of the inverse wave crest problem

    NARCIS (Netherlands)

    Peterson, Pearu; Groesen, van E.

    2001-01-01

    In a previous paper [Physica D 141 (3-4) (2000) 316], the inverse problem for wave crests was introduced and a solution strategy for two-wave interactions was given. Here these solutions are actually constructed, in particular for the cases with small interaction angle, moderate phase shifts, and/or

  11. Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines.

    Science.gov (United States)

    Lauriol, Jessica; Cabrera, Janel R; Roy, Ashbeel; Keith, Kimberly; Hough, Sara M; Damilano, Federico; Wang, Bonnie; Segarra, Gabriel C; Flessa, Meaghan E; Miller, Lauren E; Das, Saumya; Bronson, Roderick; Lee, Kyu-Ho; Kontaridis, Maria I

    2016-08-01

    Hypertrophic cardiomyopathy is a common cause of mortality in congenital heart disease (CHD). Many gene abnormalities are associated with cardiac hypertrophy, but their function in cardiac development is not well understood. Loss-of-function mutations in PTPN11, which encodes the protein tyrosine phosphatase (PTP) SHP2, are implicated in CHD and cause Noonan syndrome with multiple lentigines (NSML), a condition that often presents with cardiac hypertrophic defects. Here, we found that NSML-associated hypertrophy stems from aberrant signaling mechanisms originating in developing endocardium. Trabeculation and valvular hyperplasia were diminished in hearts of embryonic mice expressing a human NSML-associated variant of SHP2, and these defects were recapitulated in mice expressing NSML-associated SHP2 specifically in endothelial, but not myocardial or neural crest, cells. In contrast, mice with myocardial- but not endothelial-specific NSML SHP2 expression developed ventricular septal defects, suggesting that NSML-associated mutations have both cell-autonomous and nonautonomous functions in cardiac development. However, only endothelial-specific expression of NSML-associated SHP2 induced adult-onset cardiac hypertrophy. Further, embryos expressing the NSML-associated SHP2 mutation exhibited aberrant AKT activity and decreased downstream forkhead box P1 (FOXP1)/FGF and NOTCH1/EPHB2 signaling, indicating that SHP2 is required for regulating reciprocal crosstalk between developing endocardium and myocardium. Together, our data provide functional and disease-based evidence that aberrant SHP2 signaling during cardiac development leads to CHD and adult-onset heart hypertrophy. PMID:27348588

  12. Migratory neuronal progenitors arise from the neural plate borders in tunicates.

    Science.gov (United States)

    Stolfi, Alberto; Ryan, Kerrianne; Meinertzhagen, Ian A; Christiaen, Lionel

    2015-11-19

    The neural crest is an evolutionary novelty that fostered the emergence of vertebrate anatomical innovations such as the cranium and jaws. During embryonic development, multipotent neural crest cells are specified at the lateral borders of the neural plate before delaminating, migrating and differentiating into various cell types. In invertebrate chordates (cephalochordates and tunicates), neural plate border cells express conserved factors such as Msx, Snail and Pax3/7 and generate melanin-containing pigment cells, a derivative of the neural crest in vertebrates. However, invertebrate neural plate border cells have not been shown to generate homologues of other neural crest derivatives. Thus, proposed models of neural crest evolution postulate vertebrate-specific elaborations on an ancestral neural plate border program, through acquisition of migratory capabilities and the potential to generate several cell types. Here we show that a particular neuronal cell type in the tadpole larva of the tunicate Ciona intestinalis, the bipolar tail neuron, shares a set of features with neural-crest-derived spinal ganglia neurons in vertebrates. Bipolar tail neuron precursors derive from caudal neural plate border cells, delaminate and migrate along the paraxial mesoderm on either side of the neural tube, eventually differentiating into afferent neurons that form synaptic contacts with both epidermal sensory cells and motor neurons. We propose that the neural plate borders of the chordate ancestor already produced migratory peripheral neurons and pigment cells, and that the neural crest evolved through the acquisition of a multipotent progenitor regulatory state upstream of multiple, pre-existing neural plate border cell differentiation programs. PMID:26524532

  13. 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 to...... generate power. Model tests have been performed using scale models (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 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 mechanical power available to the power take off....

  14. CREST guide:the cognitive interview

    OpenAIRE

    Milne, Rebecca Jane

    2016-01-01

    This CREST Guide is an overview of an interviewing protocol – the Cognitive Interview – which aims to improve the recall of accurate and reliable information from interviewees. The Cognitive Interview is a theory and evidence-based approach which addresses three primary psychological processes that underlie interviews with cooperative interviewees: 1. the social dynamics between the interviewee and interviewer; 2. the interviewee’s and interviewer’s cognitive processes; and 3. communication b...

  15. Catching the wave at its crest.

    Science.gov (United States)

    Schenke, R

    1995-09-01

    Leland Kaiser, PhD, a long-time member of the ACPE faculty, describes opportunities in terms of surfers. Many smaller and insignificant waves will appear before the surfer senses "the big one." The knowledgeable and skilled surfer will distinguish these small waves (mere fads in management terms) from the real one (a significant trend for the medical manager). If the surfer catches the big wave before its crest, there is a formidable danger of being too far in front and being crushed by it. If the surfer misjudges the wave and starts behind the crest, the wave will leave the surfer behind. It is only by catching the wave at or near its crest that the surfer has a chance for a long and exciting ride. And, of course, even having judged the wave perfectly, there is no guarantee of success. The surfer must still use his or her skills with daring and precision if the ride is to end in the calmer waters of the shore and not in the toss and tumble of a spill. PMID:10161232

  16. Laboratory Experiments on Low-crested Breakwaters

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  17. Vesicularity of basalt erupted at Reykjanes Ridge crest

    Science.gov (United States)

    Duffield, W.A.

    1978-01-01

    Average vesicularity of basalt drilled at three sites on the west flank of the Reykjanes Ridge increases with decreasing age. This change apparently records concomitant decrease in water depth at the ridge crest where the basalt was erupted and suggests substantial upward growth of the crest during the past 35 Myr. ?? 1978 Nature Publishing Group.

  18. 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 scal...

  19. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  20. Neural tube closure in Xenopus laevis involves medial migration, directed protrusive activity, cell intercalation and convergent extension.

    Science.gov (United States)

    Davidson, L A; Keller, R E

    1999-10-01

    We have characterized the cell movements and prospective cell identities as neural folds fuse during neural tube formation in Xenopus laevis. A newly developed whole-mount, two-color fluorescent RNA in situ hybridization method, visualized with confocal microscopy, shows that the dorsal neural tube gene xpax3 and the neural-crest-specific gene xslug are expressed far lateral to the medial site of neural fold fusion and that expression moves medially after fusion. To determine whether cell movements or dynamic changes in gene expression are responsible, we used low-light videomicroscopy followed by fluorescent in situ and confocal microscopy. These methods revealed that populations of prospective neural crest and dorsal neural tube cells near the lateral margin of the neural plate at the start of neurulation move to the dorsal midline using distinctive forms of motility. Before fold fusion, superficial neural cells apically contract, roll the neural plate into a trough and appear to pull the superficial epidermal cell sheet medially. After neural fold fusion, lateral deep neural cells move medially by radially intercalating between other neural cells using two types of motility. The neural crest cells migrate as individual cells toward the dorsal midline using medially directed monopolar protrusions. These movements combine the two lateral populations of neural crest into a single medial population that form the roof of the neural tube. The remaining cells of the dorsal neural tube extend protrusions both medially and laterally bringing about radial intercalation of deep and superficial cells to form a single-cell-layered, pseudostratified neural tube. While ours is the first description of medially directed cell migration during neural fold fusion and re-establishment of the neural tube, these complex cell behaviors may be involved during cavitation of the zebrafish neural keel and secondary neurulation in the posterior axis of chicken and mouse.

  1. Crested wheatgrass control and monitoring Benton Lake Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Crested wheatgrass (CWG) was planted on Benton Lake NWR at least 30 years ago, presumably to stabilize the soil where it had been disturbed in the process of...

  2. 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.

  3. Introducing Big Sagebrush into a Crested Wheatgrass Monoculture

    OpenAIRE

    Newhall, Robert L; Rasmussen, V. Philip, Jr.; Kitchen, Boyd M

    2011-01-01

    Crested wheatgrass (Agropyron desertorum or A. cristatum) has been effectively used to stabilize arid and semi-arid range sites for decades. Reestablishing native plant materials into these areas is often desirable to increase wildlife habitat and ecological diversity. Due to its competitive nature, efforts to reestablish native plants into crested wheatgrass monocultures have had limited success. Tillage will control the grass but leaves the soil vulnerable to erosion and weed invasion. This...

  4. CREST: Climate REconstruction SofTware

    Science.gov (United States)

    Chevalier, M.; Cheddadi, R.; Chase, B. M.

    2014-02-01

    Several methods currently exist to quantitatively reconstruct palaeoclimatic variables from fossil botanical data. Of these, pdf-based (probability density functions) methods have proven valuable as they can be applied to a wide range of plants assemblages. Most commonly applied to fossil pollen data, their performance, however, can be limited by the taxonomic resolution of the pollen data, as many species may belong to a given pollen-type. Consequently, the climate information associated with different species cannot sometimes not be precisely identified, resulting less accurate reconstructions. This can become particularly problematic in regions of high biodiversity. In this paper, we propose a novel pdf-based method that takes into account the different climatic requirements of each species constituting the broader pollen-type. Pdfs are fitted in two successive steps, with parametric pdfs fitted first for each species, and then a combination of those individual species pdfs into a broader single pdf to represent the pollen-type as a unit. A climate value for the pollen assemblage is estimated from the likelihood function obtained after the multiplication of the pollen-type pdfs, with each being weighted according to its pollen percentage. To test the robustness of the method, we have applied the method to southern Africa as a regional case study, and reconstructed a suite of climatic variables based on extensive botanical data derived from herbarium collections. The reconstructions proved to be accurate for both temperature and precipitation. Predictable exceptions were areas that experience conditions at the extremes of the regional climatic spectra. Importantly, the accuracy of the reconstructed values is independent from the vegetation type where the method is applied or the number of species used. The method used in this study is publicly available in a software package entitled CREST (Climate REconstruction SofTware) and will provide the opportunity to

  5. Comparison of standard TEC models with a Neural Network based TEC model using multistation GPS TEC around the northern crest of Equatorial Ionization Anomaly in the Indian longitude sector during the low and moderate solar activity levels of the 24th solar cycle

    Science.gov (United States)

    Sur, D.; Paul, A.

    2013-09-01

    The highest Total Electron Content (TEC) values in the world normally occur at Equatorial Ionization Anomaly (EIA) region resulting in largest ionospheric range delay values observed for any potential Space Based Augmentation System (SBAS). Reliable forecasting of TEC is crucial for satellite based navigation systems. The day to day variability of the location of the anomaly peak and its intensity is very large. This imposes severe limitations on the applicability of commonly used ionospheric models to the low latitude regions. It is necessary to generate a mathematical ionospheric forecasting and mapping model for TEC based on physical ionospheric influencing parameters. A model, IRPE-TEC, has been developed based on real time low latitude total electron content data using GPS measurements from a number of stations situated around the northern crest of the EIA during 2007 through 2011 to predict the vertical TEC values during the low and moderate solar activity levels of the 24th solar cycle. This model is compared with standard ionospheric models like International Reference Ionosphere (IRI) and Parameterized Ionospheric Model (PIM) to establish its applicability in the equatorial region for accurate predictions.

  6. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  7. 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.

  8. 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).

  9. Iliac Crest Avulsion Fracture in a Young Sprinter.

    Science.gov (United States)

    Casabianca, L; Rousseau, R; Loriaut, P; Massein, A; Mirouse, G; Gerometta, A; Khiami, F

    2015-01-01

    Avulsion fracture of the iliac crest is an uncommon pathology. It usually occurs in teenagers during sport activities, more common in boys. We report a case of 16-year-old male competitive sprinter, who had an avulsion of a part of the iliac crest and the anterior-superior iliac spine during a competition. The traumatism occurred during the period of acceleration phase out of the blocks which corresponds to the maximum traction phase on the tendons. Then a total loss of function of the lower limb appears forcing him to stop the run. X-ray and CT scan confirmed the rare diagnosis of avulsion of the quasitotality of the iliac crest apophysis, corresponding to Salter 2 fracture. We performed an open reduction and internal fixation with two screws, allowing a return to sport after 3 months and his personal best record in the 100 meters at the 6th postoperative month.

  10. Iliac Crest Avulsion Fracture in a Young Sprinter

    Directory of Open Access Journals (Sweden)

    L. Casabianca

    2015-01-01

    Full Text Available Avulsion fracture of the iliac crest is an uncommon pathology. It usually occurs in teenagers during sport activities, more common in boys. We report a case of 16-year-old male competitive sprinter, who had an avulsion of a part of the iliac crest and the anterior-superior iliac spine during a competition. The traumatism occurred during the period of acceleration phase out of the blocks which corresponds to the maximum traction phase on the tendons. Then a total loss of function of the lower limb appears forcing him to stop the run. X-ray and CT scan confirmed the rare diagnosis of avulsion of the quasitotality of the iliac crest apophysis, corresponding to Salter 2 fracture. We performed an open reduction and internal fixation with two screws, allowing a return to sport after 3 months and his personal best record in the 100 meters at the 6th postoperative month.

  11. 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...

  12. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  13. Neural defects and cardiac arrhythmia in fish larvae following embryonic exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47).

    Science.gov (United States)

    Lema, Sean C; Schultz, Irvin R; Scholz, Nathaniel L; Incardona, John P; Swanson, Penny

    2007-05-31

    Polybrominated diphenyl ethers (PBDEs) are added to plastics, polyurethane foam, and textiles as a flame retardant. While PBDEs play a key role in reducing loss of human life and property from fires, these flame retardants have become pervasive organic contaminants in the environment and in the tissues of fish, birds, marine mammals, and humans. Levels of PBDEs in wildlife and humans continue to rise, raising concerns about potential ecological and health risks associated with exposure to these chemicals. Nevertheless, there is little currently known about the toxicological effects of PBDE exposure. Here, we examined the developmental toxicity of the PBDE congener 2,2',4,4'-tetrabromodiphenyl ether (PBDE 47) using the zebrafish (Danio rerio) as an ontogenetic model. Zebrafish embryos were exposed continuously to dissolved phase PBDE 47 (100-5000 microg/l) beginning 3-5 h post-fertilization (hpf). Fish treated with the highest concentrations of PBDE 47 delayed hatching, had reduced growth post-hatching, and displayed an abnormal dorsal curvature of the body with flexion at the hindbrain. By 96h post-fertilization larvae exposed to PBDE 47 had significant tachycardia, which progressed into atrioventricular block arrhythmias. Microinjection of fluorescent dye into the hindbrain ventricle revealed that cerebrospinal fluid in the neural tube and brain ventricles flowed more slowly in fish larvae exposed to PBDE 47, a likely etiology for the dorsal curvature. Similar, though much less pronounced, developmental toxicity also occurred in larvae exposed to PBDE 47 only for a 20h period during early embryogenesis (3-23 hpf), suggesting that PBDEs incorporated in lipid of the egg are bioavailable and cause toxicity later in life. Taken together, this work indicates that exposure to PBDE 47 can cause morphological abnormalities, impair cardiovascular function and cerebrospinal fluid flow, and provides a tractable starting point for using the zebrafish model to explore

  14. Induced Pluripotent Stem Cells for Neural Tissue Engineering

    OpenAIRE

    Wang, Aijun; Tang, Zhenyu; Park, In-Hyun; Zhu, Yiqian; Patel, Shyam; Daley, George Q.; Song, Li

    2011-01-01

    Induced pluripotent stem cells (iPSCs) hold great promise for cell therapies and tissue engineering. Neural crest stem cells (NCSCs) are multipotent and represent a valuable system to investigate iPSC differentiation and therapeutic potential. Here we derived NCSCs from human iPSCs and embryonic stem cells (ESCs), and investigated the potential of NCSCs for neural tissue engineering. The differentiation of iPSCs and the expansion of derived NCSCs varied in different cell lines, but all NCSC l...

  15. The CREST reactive-burn model for explosives

    Directory of Open Access Journals (Sweden)

    Maheswaran M-A.

    2011-01-01

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

  16. GDNF is required for neural colonization of the pancreas.

    Science.gov (United States)

    Muñoz-Bravo, José Luis; Hidalgo-Figueroa, María; Pascual, Alberto; López-Barneo, José; Leal-Cerro, Alfonso; Cano, David A

    2013-09-01

    The mammalian pancreas is densely innervated by both the sympathetic and parasympathetic nervous systems, which control exocrine and endocrine secretion. During embryonic development, neural crest cells migrating in a rostrocaudal direction populate the gut, giving rise to neural progenitor cells. Recent studies in mice have shown that neural crest cells enter the pancreatic epithelium at E11.5. However, the cues that guide the migration of neural progenitors into the pancreas are poorly defined. In this study we identify glial cell line-derived neurotrophic factor (GDNF) as a key player in this process. GDNF displays a dynamic expression pattern during embryonic development that parallels the chronology of migration and differentiation of neural crest derivatives in the pancreas. Conditional inactivation of Gdnf in the pancreatic epithelium results in a dramatic loss of neuronal and glial cells and in reduced parasympathetic innervation in the pancreas. Importantly, the innervation of other regions of the gut remains unaffected. Analysis of Gdnf mutant mouse embryos and ex vivo experiments indicate that GDNF produced in the pancreas acts as a neurotrophic factor for gut-resident neural progenitor cells. Our data further show that exogenous GDNF promotes the proliferation of pancreatic progenitor cells in organ culture. In summary, our results point to GDNF as crucial for the development of the intrinsic innervation of the pancreas.

  17. 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.

  18. 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....

  19. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  20. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  1. Using CREST to Model Floods for the Upper Missouri Basin

    Science.gov (United States)

    Rodriguez, L.; Spelman, D.; Skym, P.; Oguamanam, M.

    2012-12-01

    The Upper Missouri River basin in Montana is prone to frequent floods during the months of May through June. During the summer of 2011, the duration of heavy rain and high snow melt caused floods in the Missouri Watershed to last for several weeks. Although organizations and citizens are aware of the flooding, the severity of any given flood is difficult to predict. Thus, a flood forecasting system would benefit the community by providing advance notice of areas prone to floods. The team addressed these issues by calibrating a fully distributed hydrological model on this region using the University of Oklahoma's Coupled Routing Excess STorage (CREST) 2.0 model. The CREST model contains ten internal parameters that must be optimized through calibration to in-situ data which was done using only remotely sensed data as inputs; these include: rainfall from TRMM, Digital Elevation Model (DEM) from SRTM, and potential evapotranspiration (PET). At a one kilometer spatial and three hour temporal resolutions, CREST was calibrated over a three year period. This calibration was unsuccessful, resulting in a maximum NSCE of just 0.24, due to the heavy impact of snow-pack melt on the hydrology of the Upper Missouri River watershed and the lack of snow melt inputs to the model. Because of this, a modeled snow melt product, which was selected to be the Snow Data Assimilation System (SNODAS), was implemented into the model for the first time. This implementation required substantial data processing prior to input as well as substantial troubleshooting within the CREST model. Additionally, the San Bernard watershed, which is in the absence of snow, was used and calibrated in the model for comparison. The arrangement of these calibrations was performed, and the necessary steps required were documented. However, the actual calibrations were not carried out due to lack of access needed in computational power and time. Significant progress was made in understanding the fundamental steps

  2. Aerodynamic Characteristics of the Crest with Membrane Attachment on Cretaceous Pterodactyloid Nyctosaurus

    Institute of Scientific and Technical Information of China (English)

    XING Lida; WU Jianghao; LU Yi; L(U) Junchang; JI Qiang

    2009-01-01

    The Nyctosaurus specimen KJ1 was reconstructed under the hypothesis that there is a membrane attached to the crest;the so-called headsail crest.The aerodynamic forces and moment acting on the headsail crest were analyzed.It was shown that KJ1 might adjust the angle of the headsail crest relative to the air current as one way to generate thrust(one of the aerodynamic forces,used to overcome body drag in forward flight)and that the magnitude of the thrust and moment could vary with the gesture angle and the relative locafion between the aerodynamic center of the headsail crest and body's center of gravity.Three scenarios were tested for comparison:the crest with membrane attachment,the crest without membrane attachment and the absence of a cranial crest.It was shown that the aerodynamic characteristics(increasing.maintaining and decreasing thrusts and moment) would have almost disappear in flight for the crest without membrane attachment and Was non-existent without the cranial crest.It is suggested from aerodynamics evidence alone that Nyctosaurus specimen KJ1 had a membrane attached to the crest and used this reconstructed form for auxiliary flight control.

  3. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  4. 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 present...... performance of the scheme. On the basis of the field observations described here, LCSs seem to work effectively under different environmental conditions, providing the opportunity to protect beaches in the context of Integrated Coastal Management....

  5. Facial expression recognition in crested macaques (Macaca nigra)

    OpenAIRE

    Micheletta, Jérôme; Whitehouse, Jamie; Parr, Lisa A.; Bridget M Waller

    2015-01-01

    Facial expressions are a main communication channel used by many different species of primate. Despite this, we know relatively little about how primates discriminate between different facial expressions, and most of what we do know comes from a restricted number of well-studied species. In this study, three crested macaques (Macaca nigra) took part in matching-to-sample tasks where they had to discriminate different facial expressions. In a first experiment, the macaques had to match a photo...

  6. 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.

  7. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  8. Evidence for paedomorphosis in Macedonian crested newt (Triturus macedonicus from Montenegro

    Directory of Open Access Journals (Sweden)

    Slijepčević Maja D.

    2015-01-01

    Full Text Available One of the most interesting heterochronic processes in the European newt (genus Triturus is paedomorphosis, a phenomenon of attaining reproductive maturity while retaining larval features. However, paedomorphosis seems to be rare in the crested newt (Triturus cristatus superspecies. In the locality Vrba, near the town of Tuzi (Montenegro, Dr Georg Džukić found paedomorphic Macedonian crested newt (Triturus macedonicus. In this paper, new evidence for this heterochronic process in the crested newt from Montenegro is reported.

  9. ghrelin调控神经生长因子信号途径介导心肌梗死后神经重构%Ghrelin inhibits cardiac neural remodeling after myocardial infarction in rats

    Institute of Scientific and Technical Information of China (English)

    王广丽; 刘磊; 邓笑伟

    2011-01-01

    Objective Ghrelin is a newly discovered peptide as an endogenous ligand for the growth hormone secretagogue receptor,and has been demonstrated to exert beneficial effect in the cardiovascular system.In the present study,we investigated whether ghrelin administration could inhibit cardiac neural remodeling and sympathetic hyperinnervation after myocardial infarction(MI).Methods Sprague-Dawley rats underwent coronary ligation to induce MI and received rat ghrelin(100μg/kg SC BID)or saline(control).Four weeks after treatment,rats were sacrificed.We examined the expression of nerve growth factor and never markers as well as the mRNA expressions of proinflammatory mediators.We also examined the NF-κB p65 protein and IκBα protein levels by western blot analysis.Results Compared to the control group,ghrelin administration significantly decreased the density of nerve fibers with positive immunostaining for GAP43 and TH,and decreased NGF mRNA and protein levels.Ghrelin also significantly suppressed interleukin-1β,tumor necrosis factor-α,and endothelin-1 mRNA expression,and inhibited NF-κB activation.In the MI rats,the mRNA expression of ET-1 at the non-infarcted zones had a significantly positive correlation with the NGF protein levels.Conclusion Treatment with ghrelin inhibited neural remodeling and sympathetic hyperinnervation,the process may be associated with the inhibition of proinflammatory response and NGF signaling.%目的 ghrelin是最近在胃中分离出来的生长激素释放肽受体的内源性配体,在心血管系统显示出了保护效应.本实验探讨了ghrelin对心肌梗死(MI)后大鼠神经重构的影响及其作用机制.方法 SD大鼠结扎冠状动脉制作MI模型作为对照组,干预组在手术后第1天开始给予ghrelin皮下注射,剂量为100μg/kg,每天两次.对照组开胸后在冠状动脉下穿线,但不结扎,给予盐水作皮下注射.经过4个星期治疗后,处死动物.检测梗死区及梗死边缘区神经生长

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-11-01

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

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

    Science.gov (United States)

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

    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 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. PMID:27535622

  12. Stroke and cardiac cell death: Two peas in a pod.

    Science.gov (United States)

    Gonzales-Portillo, Chiara; Ishikawa, Hiroto; Shinozuka, Kazutaka; Tajiri, Naoki; Kaneko, Yuji; Borlongan, Cesar V

    2016-03-01

    A close pathological link between stroke brain and heart failure may exist. Here, we discuss relevant laboratory and clinical reports demonstrating neural and cardiac myocyte cell death following ischemic stroke. Although various overlapping risk factors exist between cerebrovascular incidents and cardiac incidents, stroke therapy has largely neglected the cardiac pathological consequences. Recent preclinical stroke studies have implicated an indirect cell death pathway, involving toxic molecules, that originates from the stroke brain and produces cardiac cell death. In concert, previous laboratory reports have revealed a reverse cell death cascade, in that cardiac arrest leads to ischemic cell death in the brain. A deeper understanding of the crosstalk of cell death pathways between stroke and cardiac failure will facilitate the development of novel treatments designed to arrest the global pathology of both diseases thereby improving the clinical outcomes of patients diagnosed with stroke and heart failure.

  13. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  14. CRANIAL NEURAL CREST CELLS ON THE MOVE: THEIR ROLES IN CRANIOFACIAL DEVELOPMENT

    OpenAIRE

    Cordero, Dwight R; Brugmann, Samantha; Chu, Yvonne; Bajpai, Ruchi; Jame, Maryam; Helms, Jill A.

    2011-01-01

    The craniofacial region is assembled through the active migration of cells and the rearrangement and sculpting of facial prominences and pharyngeal arches, which consequently make it particularly susceptible to a large number of birth defects. Genetic, molecular, and cellular processes must be temporally and spatially regulated to culminate in the three-dimension structures of the face. The starting constituent for the majority of skeletal and connective tissues in the face is a pluripotent p...

  15. 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 reprogr

  16. 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

    2014-01-01

    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

  17. Elk3 is essential for the progression from progenitor to definitive neural crest cell

    OpenAIRE

    Rogers, Crystal D.; Phillips, Jacquelyn L.; Bronner, Marianne E.

    2013-01-01

    Elk3/Net/Sap2 (here referred to as Elk3) is an Ets ternary complex transcriptional repressor known for its involvement in angiogenesis during embryonic development. Although Elk3 is expressed in various tissues, additional roles for the protein outside of vasculature development have yet to be reported. Here, we characterize the early spatiotemporal expression pattern of Elk3 in the avian embryo using whole mount in situ hybridization and quantitative RT-PCR and examine the effects of its los...

  18. 76 FR 15971 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-03-22

    ... 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... Eagle Crest Energy as part of its on-going Section 7 Endangered Species Act consultation efforts. e....

  19. 76 FR 22699 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-04-22

    ... 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... Eagle Crest Energy as part of its on-going Section 7 Endangered Species Act consultation efforts. e....

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  1. A BMP regulatory network controls ectodermal cell fate decisions at the neural plate border.

    Science.gov (United States)

    Reichert, Sabine; Randall, Rebecca A; Hill, Caroline S

    2013-11-01

    During ectodermal patterning the neural crest and preplacodal ectoderm are specified in adjacent domains at the neural plate border. BMP signalling is required for specification of both tissues, but how it is spatially and temporally regulated to achieve this is not understood. Here, using a transgenic zebrafish BMP reporter line in conjunction with double-fluorescent in situ hybridisation, we show that, at the beginning of neurulation, the ventral-to-dorsal gradient of BMP activity evolves into two distinct domains at the neural plate border: one coinciding with the neural crest and the other abutting the epidermis. In between is a region devoid of BMP activity, which is specified as the preplacodal ectoderm. We identify the ligands required for these domains of BMP activity. We show that the BMP-interacting protein Crossveinless 2 is expressed in the BMP activity domains and is under the control of BMP signalling. We establish that Crossveinless 2 functions at this time in a positive-feedback loop to locally enhance BMP activity, and show that it is required for neural crest fate. We further demonstrate that the Distal-less transcription factors Dlx3b and Dlx4b, which are expressed in the preplacodal ectoderm, are required for the expression of a cell-autonomous BMP inhibitor, Bambi-b, which can explain the specific absence of BMP activity in the preplacodal ectoderm. Taken together, our data define a BMP regulatory network that controls cell fate decisions at the neural plate border.

  2. 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.

  3. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  4. Ror2 signaling is required for local upregulation of GFD6 and activation of BMP signaling at the neural plate border.

    Science.gov (United States)

    Schille, Carolin; Bayerlová, Michaela; Bleckmann, Annalen; Schambony, Alexandra

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction. PMID:27578181

  5. Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus.

    Science.gov (United States)

    Tse, Gary; Lai, Eric Tsz Him; Tse, Vivian; Yeo, Jie Ming

    2016-01-01

    Diabetes is a common endocrine disorder with an ever increasing prevalence globally, placing significant burdens on our healthcare systems. It is associated with significant cardiovascular morbidities. One of the mechanisms by which it causes death is increasing the risk of cardiac arrhythmias. The aim of this article is to review the cardiac (ion channel abnormalities, electrophysiological and structural remodelling) and extracardiac factors (neural pathway remodelling) responsible for cardiac arrhythmogenesis in diabetes. It is concluded by an outline of molecular targets for future antiarrhythmic therapy for the diabetic population. PMID:27642609

  6. STUDY ON THE RELATIONSHIP AMONG THE HEART MERIDIAN,CARDIAC REFERRED PAIN AND THE HEART

    Institute of Scientific and Technical Information of China (English)

    RONG Peijing; ZHU Bing

    2002-01-01

    @@ Purpose: The referred pain of the somatic structure, a response of the visceralgia, is often seen in clinic. But its underlying mechanisms are poorly understood. It is interested that cardiac referred pain often appears along the running course of the Heart Meridian (HM), while acupuncture of the acupoints of HM can effectively relieve cardiac pain. In the present study, the neural basis of the relationship among the HM, cardiac referred pain and the heart is investigated by using tri-labeling technique.

  7. Cardiac sodium channelopathies

    NARCIS (Netherlands)

    A.S. Amin; A. Asghari-Roodsari; H.L. Tan

    2010-01-01

    Cardiac sodium channel are protein complexes that are expressed in the sarcolemma of cardiomyocytes to carry a large inward depolarizing current (I-Na) during phase 0 of the cardiac action potential. The importance of I-Na for normal cardiac electrical activity is reflected by the high incidence of

  8. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  9. 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...... the histomorphometric measures at the iliac crest and the vertebral body. The material comprised matched sets of unilateral transiliac crest bone biopsies and lumbar vertebral bodies (L-2) from 24 women (19-96 years) and 24 men (23-95 years) selected from a larger autopsy material. Three female subjects (80, 88, and 90...... years) had a known vertebral fracture of L-2. The iliac crest biopsies and 9-mm-thick mediolateral slices of half the entire vertebral bodies were embedded in methylmetacrylate, stained with aniline blue, and scanned into a computer with a flatbed image scanner at a high resolution. With a custom...

  10. 2010 update to crested wheatgrass control and monitoring Benton Lake Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Crested wheatgrass (CWG) was planted on Benton Lake NWR at least 30 years ago, presumably to stabilize the soil where it had been disturbed in the process of...

  11. 2011 update to crested wheatgrass control and monitoring Benton Lake Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Crested wheatgrass (CWG) was planted on Benton Lake NWR at least 30 years ago, presumably to stabilize the soil where it had been disturbed in the process of...

  12. 2009 update to crested wheatgrass control and monitoring Benton Lake Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Crested wheatgrass (CWG) was planted on Benton Lake NWR at least 30 years ago, presumably to stabilize the soil where it had been disturbed in the process of...

  13. Sex-related gene and sex identification of Crested Ibis Nipponia nippon (Ciconiiformes: Threskiornithidae)

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The Crested Ibis (Nipponia nippon) is a critical endangeredspecies of the world. At present, a reintroduction program will be conducted to save this species essentially. However, because the Crested Ibise is a sexual alike bird, it is very difficult to identify the sex from the morphological character. In order to identify the sex easily and select the right individuals for captive breeding and reintroduction, the sex related gene on W chromosome was amplified and the sex of three Crested Ibises were also identified in the present study. The 262bp fragment was also sequenced, and we found that there were 13 different nucleotide sites with 2.25 of transition/transversion based on the comparison with that of the Oriental White Stork. The sequence will also provide a theoretic base for further designing specific primer for sex related gene in the Crested Ibis.

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    Debra R. Bolter

    2011-01-01

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

  16. 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....

  17. 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...

  18. 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...

  19. Maintenance and radiation protection issues of the CREST reactor

    International Nuclear Information System (INIS)

    A maintenance approach of the Compact Reversed Shear Tokamak (CREST) for high availability is proposed. Full sector removal through horizontal ports for easy maintenance is adopted in order to increase availability. Cask type sector removal machines are used to transfer the blanket/divertor sectors. Achievable availability is estimated with a maintenance period and its interval. The proposed maintenance approach allows, at least, the similar availability to that of the present nuclear plants. The estimated availability is acceptable from an economical viewpoint. Safety concerns related to the super-heated direct steam cycle are also examined. One of the unique concerns is due to nitrogen-16 production in the coolant. The super-heated steam must flow through the turbines within several 10 s after leaving the blanket. The requirements for shielding on the heat transfer systems are declared. Another concern is the confinement and recovery of tritium in the coolant, because a high temperature blanket may have a large tritium permeation rate. Water detritiation system proposed here would be able to control the tritium concentration in the coolant within an allowable range

  20. Crest factor optimization of the multisine waveform for bioimpedance spectroscopy

    International Nuclear Information System (INIS)

    The multisine excitation is widely used in impedance measurements to retain the advantages of the sine wave, while reducing the measurement time. Adding up sine waves increases the amplitude of the excitation signal, but, for the linearity assumption to be valid, the overall amplitude of the signal needs to be kept low. Thus, the crest factor (CF) of the excitation signal must be minimized. A novel empirical method for the minimization of the CF is described in this paper. As in the case of other known methods, the computed CF may be guaranteed to be only a local minimum. However, a systematic variation of initial parameters, which is possible due to the sparing algorithm, ensures a CF value very close or equal to the global minimum. The results of CF minimization and comparison with the results from other sources are provided. The direct CF optimization results (set of optimal phases) are not well suited for practical implementation. The influence of phase accuracy on the CF is discussed, and an algorithm for the recalculation of initial phases to the rougher set is described. It is shown that previously obtained optimization results (minimal CF) can be highly preserved, even in the case of rough phase resolutions. The CF of the multisine also depends on the frequency distribution and amplitudes of its components. The CF of multisines with several frequency distributions are compared. (paper)

  1. Probing dark matter crests with white dwarfs and IMBHs

    CERN Document Server

    Amaro-Seoane, Pau; Schödel, Rainer; Davidson, Emily; Cuadra, Jorge

    2015-01-01

    White dwarfs (WDs) are the most promising captors of dark matter (DM) particles in the crests that are expected to build up in the cores of dense stellar clusters. The DM particles could reach sufficient densities in WD cores to liberate energy through self-annihilation. The extinction associated with our Galactic Centre, the most promising region where to look for such effects, makes it impossible to detect the potential associated luminosity of the DM-burning WDs. However, in smaller stellar systems which are close enough to us and not heavily extincted, such as $\\omega-$Cen, we may be able to detect DM-burning WDs. We investigate the prospects of detection of DM-burning WDs in a stellar cluster harbouring an IMBH, which leads to higher densities of DM at the centre as compared with clusters without one. We calculate the capture rate of WIMPs by a WD around an IMBH and estimate the luminosity that a WD would emit depending on its distance to the center of the cluster. Direct-summation $N-$body simulations o...

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

    Science.gov (United States)

    Aureli, Filippo; Yates, Kerrie

    2010-02-23

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

  3. Dance Drama Crested Ibises Staged at National Center for the Performing Arts

    Institute of Scientific and Technical Information of China (English)

    Our; Staff; Reporter

    2015-01-01

    "By the floating mist of the lake,several pink feathered crested ibises are flying slowly across the crimson rays of the setting sun,causing rhythmic ripples with their red feet,quietly and elegantly……"The premiere of a fascinating and poetic dance drama was staged at the Opera House of the National Center for the Performing Arts(NCPA)on December 9,2014.Crested Ibises,jointly

  4. 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...

  5. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    NARCIS (Netherlands)

    Baardman, Maria E.; Zwier, Mathijs V.; Wisse, Lambertus J.; Gittenberger-de Groot, Adriana C.; Kerstjens-Frederikse, Wilhelmina S.; Hofstra, Robert M. W.; Jurdzinski, Angelika; Hierck, Beerend P.; Jongbloed, Monique R. M.; Berger, Rolf M. F.; Plosch, Torsten; DeRuiter, Marco C.

    2016-01-01

    Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascul

  6. BASIC CRITERIA OF IRANIAN COMMERCIAL TOOTHPASTES AND AN ADA APPROVED BRAND (CREST

    Directory of Open Access Journals (Sweden)

    N NOUR BAKHSH

    2003-03-01

    Full Text Available Introduction: The effectiveness of fluorided toothpastes in reducing dental caries is well-documented, However not all fluorided toothpastes are equally effective. The objective of this study was to compare some essential criteria of six different toothpastes manufactured in Iran with one brand of ADA approved toothpaste (Crest. Methods. Six commercial toothpastes produced in Iran named as Paveh, Puneh, Nasim, Darugar, golpasand and saviz were compared with Crest in three subjects as follows: 1. Amount of fluoride concentration 2. Amount of releasing fluoride 3. Cleaning efficiency. Two first criteria were tested using the potentiometric method with F- Ion specific electrode, and Cleaning efficiency was done by O'Leary index on 60 volunteers (10 for each toothpaste. Results: Fluoride Concentration in Paveh, Puneh, Nasim toothpastes were nearly700PPM,while in three others were much lower. The highest amount of fluoride was seen in Crest (1450 PPM. Cleaning efficiency of Darugar was better than Crest, Paveh, Puneh. Cleaning efficiency of Nasim was the same as Crest and Golpasand and Saviz were weaker than Crest. Discussion: Since at the present time, the most effective, Cost-benefit method for preventive aspects of fluoride, especially in developing countries is obtained by fluoride toothpastes. Manufactures should improve quality of fluoride toothpastes, ensure that all pates maximize Fluoride bioavailability, develop active agents to help better cleaning efficiency and label products clearly with containig fluoride in PPM.

  7. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  8. Facial expression recognition in crested macaques (Macaca nigra).

    Science.gov (United States)

    Micheletta, Jérôme; Whitehouse, Jamie; Parr, Lisa A; Waller, Bridget M

    2015-07-01

    Facial expressions are a main communication channel used by many different species of primate. Despite this, we know relatively little about how primates discriminate between different facial expressions, and most of what we do know comes from a restricted number of well-studied species. In this study, three crested macaques (Macaca nigra) took part in matching-to-sample tasks where they had to discriminate different facial expressions. In a first experiment, the macaques had to match a photograph of a facial expression to another exemplar of the same expression produced by a different individual, against examples of one of three other types of expressions and neutral faces. In a second experiment, they had to match a dynamic video recording of a facial expression to a still photograph of another exemplar of the same facial expression produced by another individual, also against one of four other expressions. The macaques performed above chance in both tasks, identifying expressions as belonging to the same category regardless of individual identity. Using matrix correlations and multidimensional scaling, we analysed the pattern of errors to see whether overall similarity between facial expressions and/or specific morphological features caused the macaques to confuse facial expressions. Overall similarity, measured with the macaque facial action coding system (maqFACS), did not correlate with performances. Instead, functional similarities between facial expressions could be responsible for the observed pattern of error. These results expand previous findings to a novel primate species and highlight the potential of using video stimuli to investigate the perception and categorisation of visual signals in primates. PMID:25821924

  9. Probing dark matter crests with white dwarfs and IMBHs

    Science.gov (United States)

    Amaro-Seoane, P.; Casanellas, J.; Schödel, R.; Davidson, E.; Cuadra, J.

    2016-06-01

    White dwarfs (WDs) are the most promising captors of dark matter (DM) particles in the crests that are expected to build up in the cores of dense stellar clusters. The DM particles could reach sufficient densities in WD cores to liberate energy through self-annihilation. The extinction associated with our Galactic Centre makes it impossible to detect the potential-associated luminosities, contrary to smaller stellar systems which are close enough to us and not heavily extincted, such as -Cen. We investigate the prospects of detection of DM-burning WDs in a stellar cluster harbouring an intermediate-mass black hole (IMBH), which leads to higher densities of DM at the centre. We calculate the capture rate and estimate the luminosity that a WD would emit depending on its distance to the centre of the cluster. Direct-summation N-body simulations of -Cen yield a non-negligible number of WDs in the range of radii of interest. We apply our assumption to published Hubble Space Telescope/Advanced Camera for Surveys observations of stars in the centre of -Cen and, although we are not able to identify any evident candidate, we proof that their bunching up at high luminosities would be unique. We predict that DM burning will lead to a truncation of the cooling sequence at the faint end. The detection of DM burning in future observations of dense stellar clusters could allow us to probe different models of DM distributions and characteristics. On the other hand, if DM-burning WDs really exist, their number and properties could give hints to the existence of IMBHs.

  10. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  11. 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.

  12. 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.

  13. A statistical study of equatorial ionospheric anomaly single crest from SWARM satellite

    Science.gov (United States)

    Fathy, Adel; Ghamry, Essam

    2016-07-01

    However the, the Equatorial Ionospheric Anomaly (EIA) is being represented by two crests within ±15 degree in latitudes, a single crest is being observed in the entire ionosphere. A statistical study of 1351 EIA single crest for ionospheric electron density from SWARM-A satellite are investigated within the interval April 2014 to April 2015. Our analysis focused on local time, seasonal and both geographic and geomagnetic latitudinal variations in addition EIA amplitude with respect to solar and geomagnetic activities. Our results showed that the maximum number of EIA single crest events peak mainly in the dayside region around 1000-1200 LT. The electron density amplitude of the EIA single crest events in the dayside region jumps to 3 times its dawn and nightside amplitude. Spring events observed very close to the magnetic equator in comparison to other seasons. Their maximum number occurs within the magnetic equator, while their seasonal distribution showed that the majority of winter events located in the southern hemisphere, while spring events are centered around the magnetic equator. Regardless of local time or longitudinal location of summer events, it always has smaller amplitude in comparison with other seasons. Seasonal distribution showed that the average number of EIA single crests per month is approximately 200 events with relatively large number of events in September than March. Also it showed two maxima at spring and autumn, and two minima at summer and winter. The average magnetic latitude of summer events is +10 degrees in northern hemisphere. The majority of dawnside and nightside summer events is located in northern hemisphere and reverses its location in winter, while dayside and duskside events seem to be centered within the magnetic equator. The EIA solar and magnetic activity dependence showed that almost EIA single crest events occurred at low and moderate activity which is in partial agreement with previous studies and dayside events

  14. Marketing cardiac CT programs.

    Science.gov (United States)

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing.

  15. Modified theoretical stage-discharge relation for circular sharp-crested weirs

    Directory of Open Access Journals (Sweden)

    Rasool GHOBADIAN

    2012-03-01

    Full Text Available A circular sharp-crested weir is a circular control section used for measuring flow in open channels, reservoirs, and tanks. As flow measuring devices in open channels, these weirs are placed perpendicular to the sides and bottoms of straight-approach channels. Considering the complex patterns of flow passing over circular sharp-crested weirs, an equation having experimental correlation coefficients was used to extract a stage-discharge relation for weirs. Assuming the occurrence of critical flow over the weir crest, a theoretical stage-discharge relation was obtained in this study by solving two extracted non-linear equations. To study the precision of the theoretical stage-discharge relation, 58 experiments were performed on six circular weirs with different diameters and crest heights in a 30 cm-wide flume. The results show that, for each stage above the weirs, the theoretically calculated discharge is less than the measured discharge, and this difference increases with the stage. Finally, the theoretical stage-discharge relation was modified by exerting a correction coefficient which is a function of the ratio of the upstream flow depth to the weir crest height. The results show that the modified stage-discharge relation is in good agreement with the measured results.

  16. 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.

  17. 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.

  18. 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.

  19. Parasympathetic neural activity accounts for the lowering of exercise heart rate at high altitude

    DEFF Research Database (Denmark)

    Boushel, Robert Christopher; Calbet, J A; Rådegran, G;

    2001-01-01

    In chronic hypoxia, both heart rate (HR) and cardiac output (Q) are reduced during exercise. The role of parasympathetic neural activity in lowering HR is unresolved, and its influence on Q and oxygen transport at high altitude has never been studied.......In chronic hypoxia, both heart rate (HR) and cardiac output (Q) are reduced during exercise. The role of parasympathetic neural activity in lowering HR is unresolved, and its influence on Q and oxygen transport at high altitude has never been studied....

  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

    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......-empirical formulae for the estimation of flow depths and flow velocities across a dike. The results have been coupled to the actual erosion of the landward dike slope determined by full-scale 2D tests using the so-called “Overtopping Simulator”. This paper describes the results from 96 small-scale tests carried out...... to significantly reduce the overtopping flow velocities and flow depths on especially the landward slope of a sea dike. Moreover, the tests showed that the average flow directions on the dike crest from oblique long-crested and short-crested waves correspond approximately to the incident wave direction. Flow...

  1. Interaction among cardiac, respiratory, and locomotor rhythms during cardiolocomotor synchronization.

    Science.gov (United States)

    Niizeki, K; Kawahara, K; Miyamoto, Y

    1993-10-01

    The nature of entrainment between cardiac and locomotor rhythms was investigated while normal human subjects walked or ran on a treadmill. To detect the incidence of entrainment occurrence, the phase relationships among cardiac, respiratory, and locomotor rhythms were analyzed. The phase relationship between heartbeats and gait signals showed that entrainment of cardiac rhythm to locomotor rhythm occurred in all subjects at one or more treadmill speeds. To elucidate interactions among cardiac, respiratory, and locomotor rhythms during the cardiolocomotor synchronization, spectral and coherence analyses were done for these three rhythms. Spectral and coherence analyses on fluctuations in the heart period and respiratory rhythms revealed that the strength of coupling between cardiac and respiratory rhythms decreased in the presence of cardiolocomotor synchronization. In addition, the coupling of cardiac and locomotor rhythms appeared to induce dissociation of coupling between respiratory and locomotor rhythms. These results were similar to those observed when stepping was voluntarily synchronized with cardiac rhythm. Possible mechanisms to explain coordination and interaction among the neural oscillators innervating these three rhythms are discussed.

  2. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  3. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  4. CREST v2.1 Refined by a Distributed Linear Reservoir Routing Scheme

    Science.gov (United States)

    Shen, X.; Hong, Y.; Zhang, K.; Hao, Z.; Wang, D.

    2014-12-01

    Hydrologic modeling is important in water resources management, and flooding disaster warning and management. Routing scheme is among the most important components of a hydrologic model. In this study, we replace the lumped LRR (linear reservoir routing) scheme used in previous versions of the distributed hydrological model, CREST (coupled routing and excess storage) by a newly proposed distributed LRR method, which is theoretically more suitable for distributed hydrological models. Consequently, we have effectively solved the problems of: 1) low values of channel flow in daily simulation, 2) discontinuous flow value along the river network during flood events and 3) irrational model parameters. The CREST model equipped with both the routing schemes have been tested in the Gan River basin. The distributed LRR scheme has been confirmed to outperform the lumped counterpart by two comparisons, hydrograph validation and visual speculation of the continuity of stream flow along the river: 1) The CREST v2.1 (version 2.1) with the implementation of the distributed LRR achieved excellent result of [NSCE(Nash coefficient), CC (correlation coefficient), bias] =[0.897, 0.947 -1.57%] while the original CREST v2.0 produced only negative NSCE, close to zero CC and large bias. 2) CREST v2.1 produced more naturally smooth river flow pattern along the river network while v2.0 simulated bumping and discontinuous discharge along the mainstream. Moreover, we further observe that by using the distributed LRR method, 1) all model parameters fell within their reasonable region after an automatic optimization; 2) CREST forced by satellite-based precipitation and PET products produces a reasonably well result, i.e., (NSCE, CC, bias) = (0.756, 0.871, -0.669%) in the case study, although there is still room to improve regarding their low spatial resolution and underestimation of the heavy rainfall events in the satellite products.

  5. Unraveling the rapid radiation of crested newts (Triturus cristatus superspecies using complete mitogenomic sequences

    Directory of Open Access Journals (Sweden)

    Wielstra Ben

    2011-06-01

    Full Text Available Abstract Background The rapid radiation of crested newts (Triturus cristatus superspecies comprises four morphotypes: 1 the T. karelinii group, 2 T. carnifex - T. macedonicus, 3 T. cristatus and 4 T. dobrogicus. These vary in body build and the number of rib-bearing pre-sacral vertebrae (NRBV. The phylogenetic relationships of the morphotypes have not yet been settled, despite several previous attempts, employing a variety of molecular markers. We here resolve the crested newt phylogeny by using complete mitochondrial genome sequences. Results Bayesian inference based on the mitogenomic data yields a fully bifurcating, significantly supported tree, though Maximum Likelihood inference yields low support values. The internal branches connecting the morphotypes are short relative to the terminal branches. Seen from the root of Triturus (NRBV = 13, a basal dichotomy separates the T. karelinii group (NRBV = 13 from the remaining crested newts. The next split divides the latter assortment into T. carnifex - T. macedonicus (NRBV = 14 versus T. cristatus (NRBV = 15 and T. dobrogicus (NRBV = 16 or 17. Conclusions We argue that the Bayesian full mitochondrial DNA phylogeny is superior to previous attempts aiming to recover the crested newt species tree. Furthermore, our new phylogeny involves a maximally parsimonious interpretation of NRBV evolution. Calibrating the phylogeny allows us to evaluate potential drivers for crested newt cladogenesis. The split between the T. karelinii group and the three other morphotypes, at ca. 10.4 Ma, is associated with the separation of the Balkan and Anatolian landmasses (12-9 Ma. No currently known vicariant events can be ascribed to the other two splits, first at ca. 9.3 Ma, separating T. carnifex - T. macedonicus, and second at ca. 8.8 Ma, splitting T. cristatus and T. dobrogicus. The crested newt morphotypes differ in the duration of their annual aquatic period. We speculate on the role that this ecological

  6. SMOOTH MUSCLE STEM CELLS

    Science.gov (United States)

    Vascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well-studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, includ...

  7. Avulsion fracture of the iliac crest in a child☆☆☆

    Science.gov (United States)

    Mortati, Rafael Borghi; Borghi Mortati, Lucas; Silva Teixeira, Matheus; Itiro Takano, Marcelo; Armelin Borger, Richard

    2014-01-01

    Avulsion fractures of the apophysis of the iliac crest have rare incidence and are little known. In this article, we report the case of an 11-year-old female patient who presented this injury after indirect trauma. From careful radiographic analysis, an avulsion fracture of the iliac crest was identified. It was decided to use nonsurgical treatment comprising analgesia and load restriction. This case report emphasizes the importance of suspecting avulsion fractures in cases of low-energy trauma, and also guides the treatment, so as to prevent functional deficit and deformities. PMID:26229818

  8. 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......, the Draupner New Year Wave, shows a good agreement in the mean, indicating that this second order wave can be a good identifier of the shape and occurrence of extreme wave events. A discussion on its use as an initial condition for a fully non-linear three-dimensional surface wave analysis is given....

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  10. [Cardiac evaluation before non-cardiac surgery].

    Science.gov (United States)

    Menzenbach, Jan; Boehm, Olaf

    2016-07-01

    Before non-cardiac surgery, evaluation of cardiac function is no frequent part of surgical treatment. European societies of anesthesiology and cardiology published consensus-guidelines in 2014 to present a reasonable approach for preoperative evaluation. This paper intends to differentiate the composite of perioperative risk and to display the guidelines methodical approach to handle it. Features to identify patients at risk from an ageing population with comorbidities, are the classification of surgical risk, functional capacity and risk indices. Application of diagnostic means, should be used adjusted to this risk estimation. Cardiac biomarkers are useful to discover risk of complications or mortality, that cannot be assessed by clinical signs. After preoperative optimization and perioperative cardiac protection, the observation of the postoperative period remains, to prohibit complications or even death. In consideration of limited resources of intensive care department, postoperative ward rounds beyond intensive care units are considered to be an appropriate instrument to avoid or recognize complications early to reduce postoperative mortality. PMID:27479258

  11. Cardiac metabolism and arrhythmias

    OpenAIRE

    Barth, Andreas S.; Tomaselli, Gordon F.

    2009-01-01

    Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all deaths in the U.S.1, 2 The major causes of sudden cardiac death in adults age 35 and older are coronary artery disease (70–80%) and dilated cardiomyopathy (10–15%).3 At the molecular level, a wide variety of mechanisms contribute to arrhythmias that cause sudden cardiac death, ranging from genetic predisposition (rare mutations and common polymorphisms in ion channels and structural...

  12. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O;

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed...... and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  13. Prospective use of skin-derived precursors in neural regeneration

    Institute of Scientific and Technical Information of China (English)

    LU Xiao-cheng; TAO Yi; LI Li-xin

    2012-01-01

    Objective To review recent studies concerning the origins of skin-derived precursors (SKPs),their differentiation characteristics,and their potential application in neural regenerative medicine.Data sources Data were retrieved from studies reported in PubMed published between April,1974 and June,2012.The search terms used were "skin-derived precursors","stem cells",and "neural diseases".Study selection Articles were included in the review if they were relevant to SKPs as stem cells,as well as their applications in neural regenerative medicine,such as in the treatment of spinal cord injury,Parkinson's disease,spinal muscular atrophy and Shah-Waardenburg syndrome.Results SKPs are a novel population of neural crest-derived precursors that arise during embryogenesis and persist into adulthood.They can generate both neural cells and mesodermal lineage cells (including smooth muscle cells and adipocytes).Compared with other stem cells,SKPs are abundant in adult skin,can differentiate easily into neural cells,and are not associated with any ethical controversies.Conclusion SKPs may provide an alternative source of stem cells to embryonic stem cells for transplantation therapy for neurological diseases.

  14. 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.

  15. Calibration of reaction rates for the CREST reactive-burn model

    Science.gov (United States)

    Handley, Caroline

    2015-06-01

    In recent years, the hydrocode-based CREST reactive-burn model has had success in modelling a range of shock initiation and detonation propagation phenomena in polymer bonded explosives. CREST uses empirical reaction rates that depend on a function of the entropy of the non-reacted explosive, allowing the effects of initial temperature, porosity and double-shock desensitisation to be simulated without any modifications to the model. Until now, the sixteen reaction-rate coefficients have been manually calibrated by trial and error, using hydrocode simulations of a subset of sustained-shock initiation gas-gun experiments and the detonation size-effect curve for the explosive. This paper will describe the initial development of an automatic method for calibrating CREST reaction-rate coefficients, using the well-established Particle Swarm Optimisation (PSO) technique. The automatic method submits multiple hydrocode simulations for each ``particle'' and analyses the results to determine the ``misfit'' to gas-gun and size-effect data. Over ~40 ``generations,'' the PSO code finds a best set of reaction-rate coefficients that minimises the misfit. The method will be demonstrated by developing a new CREST model for EDC32, a conventional high explosive.

  16. Management of Vascular Risk Factors in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)

    OpenAIRE

    Meschia, James F; Voeks, Jenifer H.; Leimgruber, Pierre P.; Mantese, Vito A.; Timaran, Carlos H; Chiu, David; Bart M. Demaerschalk; Howard, Virginia J; Hughes, Susan E.; Longbottom, Mary; Howard, Annie Green; Brott, Thomas G

    2014-01-01

    Background The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) is a multicenter randomized trial of stenting versus endarterectomy in patients with symptomatic and asymptomatic carotid disease. This study assesses management of vascular risk factors. Methods and Results Management was provided by the patient's physician, with biannual monitoring results collected by the local site. Therapeutic targets were low‐density lipoprotein, cholesterol

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  18. Overtopping Flow Impact on a Vertical Wall on a Dike Crest

    NARCIS (Netherlands)

    Chen, X.; Hofland, B.; Altomare, C.; Uijttewaal, J.S.W.

    2014-01-01

    In this paper the impact process and mechanism of overtopping flow on a vertical wall on a dike crest are investigated by means of a series of physical model tests. A double-peaked force was recognized in a time series of an overtoping flow. Four stages were summarized for the whole overtopping flow

  19. Genomic diversity and evolution of the head crest in the rock pigeon

    DEFF Research Database (Denmark)

    Shapiro, Michael D.; Kronenberg, Zev; Li, Cai;

    2013-01-01

    populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate...

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

    DEFF Research Database (Denmark)

    Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander;

    2015-01-01

    Real-time systems need time-predictable platforms to allow static analysis of the worst-case execution time (WCET). Standard multi-core processors are optimized for the average case and are hardly analyzable. Within the T-CREST project we propose novel solutions for time-predictable multi-core ar...

  1. 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...

  2. 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....

  3. 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...

  4. 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...

  5. 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.

  6. 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. T

  7. Territorial behaviour in Crested Newt Triturus cristatus and Marbled Newt T. Marmoratus (Amphibia, Urodela)

    NARCIS (Netherlands)

    Zuiderwijk, Annie; Sparreboom, Max

    1986-01-01

    Mating and premating behaviour of the Crested Newt Triturus cristatus and the Marbled Newt T. marmoratus were studied in both the natural habitat and aquaria. Attention is focussed on male interactions. During the breeding period, males occupy open spots on the bottom of a pond defending these again

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

    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

  10. Geographic variation and taxonomy of crested newts (Triturus cristatus superspecies): morphological and mitochondrial DNA data

    NARCIS (Netherlands)

    Arntzen, J.W.; Wallis, Graham P.

    1999-01-01

    Within the newt genus Triturus, the large-bodied species in the T. cristatus (crested newt) superspecies show an unusual degree of variation in relative trunk length as a result of among-taxon variation in interlimb vertebral count. Here we examine the systematic value of this feature as assessed by

  11. Ridge Expansion by Flapless Split Crest and Immediate Implant Placement: Evolution of the Technique.

    Science.gov (United States)

    Cortese, Antonio; Pantaleo, Giuseppe; Amato, Massimo; Claudio, Pier Paolo

    2016-03-01

    Various treatment strategies and techniques have been proposed to perform alveolar bone augmentation; most common are guided bone regeneration, split crest, and autologous bone grafting. All of these techniques are reported to possess bone regenerative properties of osteoinduction and osteoconduction in relation to regenerated bone survival. Split crest resulted to be one of the most reliable bone augmentation techniques. In this study, we describe a new flapless-modified split crest technique on 4 patients to optimize the bone regeneration with bone augmentation implant insertion in 1 single stage. The rationale of this technique is to obtain a proper buccal cortex expansion preserving its vascular supply and avoiding periosteal elevation for better cortical bone preservation. The main advantages of this technique consist in a single surgical stage without donor sites, vascular periosteal preservation of vestibular cortical walls, preservation of alveolar bone height avoiding bone loss after implant kit drilling, and preservation of proper cortical thickness on both sides, thereby saving periosteal nourishment on the vestibular side. Indication for this technique could be extended to almost every implant insertion for alveolar height saving at drilling time for implant insertion, because of the alveolar crest shape. PMID:26845089

  12. 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.

  13. Neural Engineering

    Science.gov (United States)

    He, Bin

    About the Series: Bioelectric Engineering presents state-of-the-art discussions on modern biomedical engineering with respect to applications of electrical engineering and information technology in biomedicine. This focus affirms Springer's commitment to publishing important reviews of the broadest interest to biomedical engineers, bioengineers, and their colleagues in affiliated disciplines. Recent volumes have covered modeling and imaging of bioelectric activity, neural engineering, biosignal processing, bionanotechnology, among other topics.

  14. Cardiac Risk Assessment

    Science.gov (United States)

    ... to assess cardiac risk include: High-sensitivity C-reactive protein (hs-CRP) : Studies have shown that measuring ... LDL-C but does not respond to typical strategies to lower LDL-C such as diet, exercise, ...

  15. Sudden Cardiac Arrest

    Science.gov (United States)

    ... Heart Risk Factors & Prevention Heart Diseases & Disorders Atrial Fibrillation (AFib) Sudden Cardiac Arrest (SCA) SCA: Who's At Risk? Prevention of SCA What Causes SCA? SCA Awareness Atrial Flutter Heart Block Heart Failure Sick Sinus Syndrome Substances & Heart Rhythm Disorders Symptoms & ...

  16. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;

    2012-01-01

    to a standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social......Aim: The comprehensive cardiac rehabilitation (CR) programme after myocardial infarction (MI) improves quality of life and results in reduced cardiac mortality and recurrence of MI. Hospitals worldwide face problems with low participation rates in rehabilitation programmes. Inequality...

  17. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  18. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  19. Cardiac rehabilitation in Germany.

    Science.gov (United States)

    Karoff, Marthin; Held, Klaus; Bjarnason-Wehrens, Birna

    2007-02-01

    The purpose of this review is to give an overview of the rehabilitation measures provided for cardiac patients in Germany and to outline its legal basis and outcomes. In Germany the cardiac rehabilitation system is different from rehabilitation measures in other European countries. Cardiac rehabilitation in Germany since 1885 is based on specific laws and the regulations of insurance providers. Cardiac rehabilitation has predominantly been offered as an inpatient service, but has recently been complemented by outpatient services. A general agreement on the different indications for offering these two services has yet to be reached. Cardiac rehabilitation is mainly offered after an acute cardiac event and bypass surgery. It is also indicated in severe heart failure and special cases of percutaneous coronary intervention. Most patients are men (>65%) and the age at which events occur is increasing. The benefits obtained during the 3-4 weeks after an acute event, and confirmed in numerous studies, are often later lost under 'usual care' conditions. Many attempts have been made by rehabilitation institutions to improve this deficit by providing intensive aftercare. One instrument set up to achieve this is the nationwide institution currently comprising more than 6000 heart groups with approximately 120000 outpatients. After coronary artery bypass grafting or acute coronary syndrome cardiac rehabilitation can usually be started within 10 days. The multidisciplinary rehabilitation team consists of cardiologists, psychologists, exercise therapists, social workers, nutritionists and nurses. The positive effects of cardiac rehabilitation are also important economically, for example, for the improvement of secondary prevention and vocational integration. PMID:17301623

  20. Cardiac tumours in infancy

    OpenAIRE

    Yadava, O.P.

    2012-01-01

    Cardiac tumours in infancy are rare and are mostly benign with rhabdomyomas, fibromas and teratomas accounting for the majority. The presentation depends on size and location of the mass as they tend to cause cavity obstruction or arrhythmias. Most rhabdomyomas tend to regress spontaneously but fibromas and teratomas generally require surgical intervention for severe haemodynamic or arrhythmic complications. Other relatively rare cardiac tumours too are discussed along with an Indian perspect...

  1. Infected cardiac hydatid cyst

    OpenAIRE

    Ceviz, M; Becit, N; Kocak, H.

    2001-01-01

    A 24 year old woman presented with chest pain and palpitation. The presence of a semisolid mass—an echinococcal cyst or tumour—in the left ventricular apex was diagnosed by echocardiography, computed tomography, and magnetic resonance imaging. The infected cyst was seen at surgery. The cyst was removed successfully by using cardiopulmonary bypass with cross clamp.


Keywords: cardiac hydatid cyst; infected cardiac hydatid cyst

  2. A pilot study investigating the utilization of crest pads for treatment of toe callus and ulceration.

    Science.gov (United States)

    Melo, Monica; Bernecker, Tricia; McCullough, James; Hong, John; Trumbauer, Jane Scott; Miller, Mary Ellen

    2015-12-01

    Patients with lesser-toe deformities are at increased risk of developing calluses and ulcers on the distal ends of the affected digits because of the increased pressures applied to these areas. The number of diabetic patients in the United States continues to increase, along with associated comorbidities such as peripheral vascular disease and peripheral neuropathy. These conditions predispose patients to developing foot ulcerations, especially if foot deformities are present. Crest pads are a simple-to-make, inexpensive option to treat calluses and ulcerations on the distal ends of digits; however, there is no research available that support their use. Crest pads consist of rolled gauze covered in moleskin, with a large opening that fits over several toes and lies on the dorsal aspect of the foot, with the padded portion resting under the toes. Over several days of use, the pad molds to the plantar aspect of the toes, offloading pressure from the distal end of the affected digit(s). The sample was obtained through a retrospective chart review of patients identified as having had at least one nail care visit and at least one follow-up visit at a vascular surgery practice between August 2011 and December 2014. Potential subjects with toe deformities who presented with callus or ulcer on the distal end of a digit were considered for inclusion, if they received a crest pad as part of their treatment plan. The scholarly project was a preintervention or postintervention design with subjects acting as their own controls. McNemar's test was used to analyze the results which were statistically significant (P ulcer improvement following the crest pad intervention. The results of this scholarly project support the use of crest pads in patients with lesser-toe deformities to treat distal toe calluses and/or ulcerations.

  3. A pilot study investigating the utilization of crest pads for treatment of toe callus and ulceration.

    Science.gov (United States)

    Melo, Monica; Bernecker, Tricia; McCullough, James; Hong, John; Trumbauer, Jane Scott; Miller, Mary Ellen

    2015-12-01

    Patients with lesser-toe deformities are at increased risk of developing calluses and ulcers on the distal ends of the affected digits because of the increased pressures applied to these areas. The number of diabetic patients in the United States continues to increase, along with associated comorbidities such as peripheral vascular disease and peripheral neuropathy. These conditions predispose patients to developing foot ulcerations, especially if foot deformities are present. Crest pads are a simple-to-make, inexpensive option to treat calluses and ulcerations on the distal ends of digits; however, there is no research available that support their use. Crest pads consist of rolled gauze covered in moleskin, with a large opening that fits over several toes and lies on the dorsal aspect of the foot, with the padded portion resting under the toes. Over several days of use, the pad molds to the plantar aspect of the toes, offloading pressure from the distal end of the affected digit(s). The sample was obtained through a retrospective chart review of patients identified as having had at least one nail care visit and at least one follow-up visit at a vascular surgery practice between August 2011 and December 2014. Potential subjects with toe deformities who presented with callus or ulcer on the distal end of a digit were considered for inclusion, if they received a crest pad as part of their treatment plan. The scholarly project was a preintervention or postintervention design with subjects acting as their own controls. McNemar's test was used to analyze the results which were statistically significant (P < .0001 at first callus follow-up and P = .0002 at second callus follow-up) for callus, hemorrhagic callus, and/or ulcer improvement following the crest pad intervention. The results of this scholarly project support the use of crest pads in patients with lesser-toe deformities to treat distal toe calluses and/or ulcerations. PMID:26567055

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Kari D Hagen

    2011-12-01

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

  6. Cardiac applications of optogenetics.

    Science.gov (United States)

    Ambrosi, Christina M; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-08-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics.

  7. A New Brachylophosaurin Hadrosaur (Dinosauria: Ornithischia with an Intermediate Nasal Crest from the Campanian Judith River Formation of Northcentral Montana.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Freedman Fowler

    Full Text Available Brachylophosaurini is a clade of hadrosaurine dinosaurs currently known from the Campanian (Late Cretaceous of North America. Its members include: Acristavus gagslarsoni, which lacks a nasal crest; Brachylophosaurus canadensis, which possesses a flat paddle-shaped nasal crest projecting posteriorly over the dorsal skull roof; and Maiasaura peeblesorum, which possesses a dorsally-projecting nasofrontal crest. Acristavus, from the lower Two Medicine Formation of Montana (~81-80 Ma, is hypothesized to be the ancestral member of the clade. Brachylophosaurus specimens are from the middle Oldman Formation of Alberta and equivalent beds in the Judith River Formation of Montana; the upper Oldman Formation is dated 77.8 Ma.A new brachylophosaurin hadrosaur, Probrachylophosaurus bergei (gen. et sp. nov. is described and phylogenetically analyzed based on the skull and postcranium of a large individual from the Judith River Formation of northcentral Montana (79.8-79.5 Ma; the horizon is equivalent to the lower Oldman Formation of Alberta. Cranial morphology of Probrachylophosaurus, most notably the nasal crest, is intermediate between Acristavus and Brachylophosaurus. In Brachylophosaurus, the nasal crest lengthens and flattens ontogenetically, covering the supratemporal fenestrae in large adults. The smaller nasal crest of Probrachylophosaurus is strongly triangular in cross section and only minimally overhangs the supratemporal fenestrae, similar to an ontogenetically earlier stage of Brachylophosaurus. Sutural fusion and tibial osteohistology reveal that the holotype of Probrachylophosaurus was relatively more mature than a similarly large Brachylophosaurus specimen; thus, Probrachylophosaurus is not simply an immature Brachylophosaurus.The small triangular posteriorly oriented nasal crest of Probrachylophosaurus is proposed to represent a transitional nasal morphology between that of a non-crested ancestor such as Acristavus and the large flat

  8. Neural Network Applications

    NARCIS (Netherlands)

    Vonk, E.; Jain, L.C.; Veelenturf, L.P.J.

    1995-01-01

    Artificial neural networks, also called neural networks, have been used successfully in many fields including engineering, science and business. This paper presents the implementation of several neural network simulators and their applications in character recognition and other engineering areas

  9. A Method for Determination of in Run-Up Front Velocities on Dikes in Oblique and Short-Crested Waves

    DEFF Research Database (Denmark)

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

    2011-01-01

    This paper presents a physical model test study to improve description of run-up events on dikes in oblique long and short-crested waves in terms of flow depth, flow velocities and overtopping. The paper focus on the flow velocities and a new method is proposed for determining flow velocities...... and flow directions on a dike. A validation of the proposed method is made against existing semiempirical formulae and measurements from a micro-propeller in case of perpendicular long-crested waves. Moreover, the method is applied for long- and short-crested oblique waves where results show...

  10. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  11. The cardiac anxiety questionnaire: cross-validation among cardiac inpatients

    NARCIS (Netherlands)

    Beek, M.H. van; Oude Voshaar, R.C.; Deelen, F.M. van; Balkom, A.J. van; Pop, G.A.; Speckens, A.E.

    2012-01-01

    OBJECTIVE: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  12. THE CARDIAC ANXIETY QUESTIONNAIRE : CROSS-VALIDATION AMONG CARDIAC INPATIENTS

    NARCIS (Netherlands)

    van Beek, M. H. C. T.; Voshaar, R. C. Oude; van Deelen, F. M.; van Balkom, A. J. L. M.; Pop, G.; Speckens, A. E. M.

    2012-01-01

    Objective: General anxiety symptoms are common in patients with cardiac disease and considered to have an adverse effect on cardiac prognosis. The role of specific cardiac anxiety, however, is still unknown. The aim of this study is to examine the factor structure, reliability, and validity of the D

  13. Linear surface capillary-gravity short-crested waves on a current

    Institute of Scientific and Technical Information of China (English)

    HUANG Hu

    2008-01-01

    One of the forward situations in the study of water waves is the basic three-dimensional surface wave motion of short-crested waves. Capillary waves result in rich effects concerned closely with remote sensing in the open ocean. Ocean currents experience a complete process in surface wave motion. Based on the above ideas, a linear dynamical system of surface capillary-gravity short-crested waves is developed by considering the current effects, thus leading to the following analytical expressions of the kinematic and dynamic variables: the wave height, the wave steepness, the phase velocity, the wave-particle velocities, accelerations and trajectories and the wave pressure. A number of the classi-cal, typical and latest special wave cases can arise from these expressions.

  14. Implant-Prosthetic Rehabilitation in Bilateral Agenesis of Maxillary Lateral Incisors with a Mini Split Crest

    Science.gov (United States)

    Figliuzzi, M. M.; Giudice, A.; Pileggi, S.; Pacifico, D.; Marrelli, M.; Tatullo, M.; Fortunato, L.

    2016-01-01

    The reported clinical case describes the surgical procedure of ridge augmentation by using a “split crest” technique with a partial thickness flap and a subsequent implant-prosthetic rehabilitation aimed at treating a bilateral agenesis of the upper lateral incisors. In such cases with vestibule-palatal and mesial-distal scarce bone thicknesses associated with the need of a proper functional and aesthetic rehabilitation, the split crest technique is particularly suitable. In the case we reported, because of the poor bone thicknesses, we performed a minimally invasive split crest which allowed a correct insertion of the fixtures. This technique allowed us to achieve an optimal functional and aesthetic rehabilitation; moreover, we obtained a good emergency profile, ensuring the vitality of the close teeth and ensuring a good primary stability and the following osseointegration of dental implants. PMID:27190658

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

    Energy Technology Data Exchange (ETDEWEB)

    Buchowski, J.M.; Ahn, N.U.; Ahn, U.M. [Dept. of Orthopaedic Surgery, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); McCarthy, E.F. [Dept. of Orthopaedic Surgery, Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Dept. of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Mehta, M.B. [Clinical Associates, Good Samaritan Hospital, Baltimore, MD (United States)

    2001-08-01

    An 88-year-old woman with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) presented with hyperglycemia, intravascular depletion, and atrial fibrillation. The patient was found to have unusually severe calcinosis cutis in both legs extending from the knees to the ankles bilaterally, as well as Raynaud's phenomenon, sclerodactyly, and telangiectasias. The patient was normocalcemic and normophosphatemic. Although subcutaneous calcification is often seen with CREST syndrome, this case is unusual in that the area of involvement was much larger than previously described. Furthermore, the amount of calcinosis was disproportionately severe and was the major cause of symptoms and disability compared with the other components of the syndrome. (orig.)

  16. Implant-Prosthetic Rehabilitation in Bilateral Agenesis of Maxillary Lateral Incisors with a Mini Split Crest

    Directory of Open Access Journals (Sweden)

    M. M. Figliuzzi

    2016-01-01

    Full Text Available The reported clinical case describes the surgical procedure of ridge augmentation by using a “split crest” technique with a partial thickness flap and a subsequent implant-prosthetic rehabilitation aimed at treating a bilateral agenesis of the upper lateral incisors. In such cases with vestibule-palatal and mesial-distal scarce bone thicknesses associated with the need of a proper functional and aesthetic rehabilitation, the split crest technique is particularly suitable. In the case we reported, because of the poor bone thicknesses, we performed a minimally invasive split crest which allowed a correct insertion of the fixtures. This technique allowed us to achieve an optimal functional and aesthetic rehabilitation; moreover, we obtained a good emergency profile, ensuring the vitality of the close teeth and ensuring a good primary stability and the following osseointegration of dental implants.

  17. Conditional Short-crested second order waves in shallow water and with superimposed current

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher

    2004-01-01

    wave, given the value of the wave crest at a specific point in time or space. In the present paper a derivation of the expected second order short-crested wave riding on a uniform current is given. The analysis is based on the second order Sharma and Dean shallow water wave theory and the direction......For bottom-supported offshore structures like oil drilling rigs and oil production platforms, a deterministic design wave approach is often applied using a regular non-linear Stokes' wave. Thereby, the procedure accounts for non-linear effects in the wave loading but the randomness of the ocean...... waves is poorly represented, as the shape of the wave spectrum does not enter the wave kinematics. To overcome this problem and still keep the simplicity of a deterministic approach, Tromans, Anaturk and Hagemeijer (1991) suggested the use of a deterministic wave, defined as the expected linear Airy...

  18. Conditional short-crested waves in shallow water and with superimposed current

    DEFF Research Database (Denmark)

    Jensen, Jørgen Juncher

    2002-01-01

    wave, given the value of the wave crest at a specific point in time or space. In the present paper a derivation of the expected linear short-crested wave riding on a uniform current is given. The analysis is based on the conventional shallow water Airy wave theory and the direction of the main wind......For bottom-supported offshore structures like oil drilling rigs and oil production platforms, a deterministic design wave approach is often applied using a regular non-linear Stokes´ wave. Thereby, the procedure accounts for non-linear effects in the wave loading but the randomness of the ocean...... waves is poorly represented, as the shape of the wave spectrum does not enter the wave kinematics. To overcome this problem and still keep the simplicity of a deterministic approach, Tromans, Anaturk and Hagemeijer (1991) suggested the use of a deterministic wave, defined as the expected linear Airy...

  19. Malformations and body injuries in a hybrid zone of crested newts (Caudata: Salamandridae: Triturus cristatus superspecies

    Directory of Open Access Journals (Sweden)

    Zdeněk Mačát

    2015-12-01

    Full Text Available Morphological abnormalities occur frequently in wild amphibian populations. We analysed malformation and injuries in the hybrid zone of three crested newt species, in the Czech Republic. In total, 274 individuals from 35 localities in South Moravia (Czech Republic were examined during the period 2010-2014. Malformations were found in eight newts (2.9% from seven localities. Injuries were recorded on 59 newts (21.5%. Proportions of tail crest injuries was significantly higher (P ˂ 0.1 in males than in females and the probability of being injured was significantly higher (P ˂ 0.01 for adult individuals. We discuss gene mutation, parasitism and predation as possible explanations for our observations.

  20. Giant Cardiac Cavernous Hemangioma.

    Science.gov (United States)

    Unger, Eric; Costic, Joseph; Laub, Glenn

    2015-07-01

    We report the case of an asymptomatic giant cardiac cavernous hemangioma in a 71-year-old man. The intracardiac mass was discovered incidentally during surveillance for his prostate cancer; however, the patient initially declined intervention. On presentation to our institution 7 years later, the lesion had enlarged significantly, and the patient consented to excision. At surgery, an 8 × 6.5 × 4.8 cm intracardiac mass located on the inferior heart border was excised with an intact capsule through a median sternotomy approach. The patient had an uneventful postoperative course. We discuss the diagnostic workup, treatment, and characteristics of this rare cardiac tumor. PMID:26140782

  1. What Crested Butte Mountain Resort Feels the Ski Industry Is, In General, Looking for in College Graduates.

    Science.gov (United States)

    Jernigan, Rick

    This paper describes general employment requirements for employment candidates in the skiing industry, as seen by Crested Butte Mountain Resort personnel. General educational requirements are primarily business skills, including: communications, computers, math, finance, accounting, economics, personnel administration, and psychology. Other…

  2. The double-crested cormorant in Lake Michigan: A review of population trends, ecology and current management

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Double-crested Cormorant, or DCCO, is the most widely distributed cormorant of the six North American cormorant species. This work is an attempt to review and...

  3. Habitat use and food selection of small mammals near a sagebrush/crested wheatgrass interface in southeastern Idaho

    International Nuclear Information System (INIS)

    Research has been conducted on various aspects of the ecology of wildlife residing on and adjacent to the Subsurface Disposal Area (SDA) and one other low-level radioactive waste disposal site on the Idaho National Engineering Laboratory (INEL) in southeastern Idaho. Habitat use and food selection data were collected for deer mice (Peromyscus maniculatus), montane voles (Microtus montanus), Ord's kangaroo rats (Dipodomys ordii), and Townsend's ground squirrels (Spermophilus townsendii) near a sagebrush (Artemisia tridentata)/crested wheatgrass (Agropyron cristatum) interface. Significantly more captures occurred in the native sagebrush habitat than in areas planted in crested wheatgrass or in disturbed sites. Crested wheatgrass, a prolific seed producer, still accounted for over 30% of the total captures. Montane voles and Townsend's ground squirrels (during periods of aboveground activity) used the crested wheatgrass habitat throughout the summer, while deer mice and Ord's kangaroo rats exhibited heavy use after seed set

  4. Laboratory Research on Effective Test Area of Short-Crested Waves Generated by Two-Sided Segmented Wavemakers

    Institute of Scientific and Technical Information of China (English)

    李俊; 陈刚; 杨建民; 彭涛

    2014-01-01

    The size and shape of the effective test area are crucial to consider when short-crested waves are created by segmented wavemakers. The range of the effective test area of short-crested waves simulated by two-sided segmented wavemakers is analyzed in this paper. The experimental investigation on the wave field distribution of short-crested waves generated by two-sided segmented wavemakers is conducted by using an array of wave gauges. Wave spectra and directional spreading function are analyzed and the results show that when the main direction is at a certain angle with the normal line of wave generators, the wave field of 3D short-crested waves generated by two-sided segmented wavemakers has good spatial uniformity within the model test area. The effective test area can provide good wave environments for seakeeping model tests of various ocean engineering structures in the deep ocean engineering basin.

  5. New Results from the NOAA CREST Lidar Network (CLN) Observations in the US Eastcoast

    Science.gov (United States)

    Moshary, Fred; Han, Zaw; Wu, Yonghua; Gross, Barry; Wesloh, Daniel; Hoff, Raymond M.; Delgado, Ruben; Su, Jia; Lei, Liqiao; Lee, Robert B.; McCormick, M. Pat; Diaz, Jesus; Cruz, Carlos; Parsiani, Hamed

    2016-06-01

    This paper presents coordinated ground-based observations by the NOAA-CREST Lidar Network (CLN) for profiling of aerosols, cloud, water vapor, and wind along the US east coast including Caribbean region at Puerto Rico. The instrumentation, methodology and observation capability are reviewed. The applications to continental and intercontinental-scale transport of smoke and dust plumes, and their large scale regional impact are discussed.

  6. Correlation of Cere Color with Intra- and Interspecific Agonistic Interactions of Crested Caracaras

    OpenAIRE

    Dwyer, James F.

    2014-01-01

    Bright coloration in birds is an important indicator of individual quality often used in social displays. Structural, carotenoid-, and melanin-based colors are long-lasting, widespread, and widely studied. Hemoglobin-based colors are ephemeral, rare, and less studied. Hemoglobin-based displays occur when an individual facultatively enhances or restricts blood flow through caruncles, combs, wattles, or other highly vascularized un-feathered skin patches. In Crested Caracaras (Caracara cheriway...

  7. Effect of X-ray beam vertical angulation on radiographic assessment of alveolar crest level.

    OpenAIRE

    Zulqarnain B; Almas K

    1998-01-01

    Periodontal diseases are diagnosed and monitored by various methods. Probing pocket depth measurements and dental radiographs are two of the most commonly used methods. The aim of this study was to assess the effect of x-ray beam vertical angulation on radiographic assessment of alveolar crest level in five human mandibles. A standardized technique was used to take bitewing radiographs with -10 degrees, 0 degree and +10 degrees angulation of X-Ray beam. The range of the mean difference...

  8. New Results from the NOAA CREST Lidar Network (CLN Observations in the US Eastcoast

    Directory of Open Access Journals (Sweden)

    Moshary Fred

    2016-01-01

    Full Text Available This paper presents coordinated ground-based observations by the NOAA-CREST Lidar Network (CLN for profiling of aerosols, cloud, water vapor, and wind along the US east coast including Caribbean region at Puerto Rico. The instrumentation, methodology and observation capability are reviewed. The applications to continental and intercontinental-scale transport of smoke and dust plumes, and their large scale regional impact are discussed.

  9. Traumatic lumbar hernia repair: a laparoscopic technique for mesh fixation with an iliac crest suture anchor.

    Science.gov (United States)

    Links, D J R; Berney, C R

    2011-12-01

    Traumatic lumbar hernia (TLH) is a rare presentation. Traditionally, these have been repaired via an open approach. Recurrence can be a problem due to the often limited tissue available for mesh fixation at the inferior aspect of the hernia defect. We report the successful use of bone suture anchors placed in the iliac crest during transperitoneal laparoscopy for mesh fixation to repair a recurrent TLH. This technique may be particularly useful after previous failed attempts at open TLH repair.

  10. Population status of great crested newts (Triturus cristatus) at sites subjected to development mitigation

    OpenAIRE

    Lewis, Brett; Griffiths, Richard A.; John W. Wilkinson

    2016-01-01

    Increasing development of natural habitats frequently causes conflict with the conservation of protected species. Consequently, interventions that attempt to mitigate the impact of development are becoming increasingly commonplace. We used four approaches to assess the effectiveness of development mitigation on a species subject to widespread development pressures in Europe – the great crested newt (Triturus cristatus). Firstly, a systematic evidence review revealed eleven published studies o...

  11. Computed tomography evaluation of the iliac crest apophysis: age estimation in living individuals.

    Science.gov (United States)

    Ekizoglu, Oguzhan; Inci, Ercan; Erdil, Irem; Hocaoglu, Elif; Bilgili, Mustafa Gokhan; Kazimoglu, Cemal; Reisoglu, Ali; Can, Ismail Ozgur

    2016-07-01

    Determination of the ossification properties of the iliac apophysis is important not only in the clinical evaluation of patients undergoing orthopedic surgery but also in age estimation studies for forensic purposes. The literature includes both anthropological and radiological (conventional radiography, ultrasonography, and magnetic resonance imaging modalities) investigations of the different staging systems used for these purposes. In this study, we assessed the utility of computed tomography (CT) of the iliac crest apophysis in estimating forensic age. CT scans of the iliac crest apophysis of 380 patients (187 females, 193 males, and 10-29 years of age) were evaluated according to the four-stage system. Further subclassification did not give data properly due to the reference length measurement of the iliac wing with CT. Thus, in our series, stage 2 was first seen in 12 years of age and stage 3 in those 14 years of age in both sexes and on both sides of the pelvis. Stage 4 was first seen in 17 years of both sexes but only on the right side; on the left side, it appeared in females 18 years of age and in males 17 years of age. Present data was found consistent with previous pelvic radiographic findings. First seen ages for stage 2 and 3 are 12 and 14 years respectively which presented valuable information for legally important age thresholds. However, disadvantages of CT, including high-dose radiation exposure to gonads, the difficulty of evaluating the iliac crest, and the age boundary of 17 years, could make this method infeasible, as compared with hand wrist and pelvic radiographic methods. CT of the iliac crest has probably a greater utility where preexisting CT scans of the pelvic region are available, and it may be considered as a supportive method for age-estimation purposes. PMID:26914804

  12. Perioperative management of cardiac disease.

    Science.gov (United States)

    Aresti, N A; Malik, A A; Ihsan, K M; Aftab, S M E; Khan, W S

    2014-01-01

    Pre-existing cardiac disease contributes significantly to morbidity and mortality amongst patients undergoing non cardiac surgery. Patients with pre-existing cardiac disease or with risk factors for it, have as much as a 3.9% risk of suffering a major perioperative cardiac event (Lee et al 1999, Devereaux 2005). Furthermore, the incidence of perioperative myocardial infarction (MI) is increased 10 to 50 fold in patients with previous coronary events (Jassal 2008).

  13. Polyurethane resins derived from castor oil (Ricinus communis) for tibial crest deviation in dogs

    International Nuclear Information System (INIS)

    Medial patellar luxation is one of the most common orthopedic problems in small breeds of dogs and tibial crest deviation is a frequent accompaining anatomical abnormality. For that reason, the purpose of this study was to evaluate the behavior of castor oil derived polyurethane implants when apllied to experimental defects created on the medial side of the proximal tibia of normal puppies. Twelve dogs were randomly divided in 3 groups of 4 animals and were submitted to the same treatment. Histopathological study was performed respectively at 30 (GI), 60 (GII) and 90 (GIII) days post-surgery. Evaluations methods included clinical assessment, radiology, gross and macroscopic study, tomography and statistical analysis. Clinically, there were no signs of implant rejection. Radiology revealed intense periosteal reaction and new bone formation. On gross examination, there was thickening and lateral deviation of the tibial crest and new bone neoformation. On microscopic examination, there was fibrous tissue around the polyurethane, periosteal proliferation on the medial side of the tibia and no bone proliferation towards the implant. Cat scans reveled lateral deviation of the tibial crest in eleven animals, which was statistically significant (p<5; pared T test)

  14. EXTRACTION, QUANTIFICATION, AND MOLAR MASS DETERMINATION OF HYALURONIC ACID EXTRACTED FROM CHICKEN CREST

    Directory of Open Access Journals (Sweden)

    C. S. ROSA

    2008-11-01

    Full Text Available

    Hyaluronic acid (HA is part of the connective tissue. The polymer is composed of alternating units of ß-d-glucuronic acid and N-acetyl-ß-d-glucosamine linked, respectively, via 1-3 and 1-4 bonds. The chicken crest is one of the richest tissues in this polysaccharide. Since Brazil is one of the main chicken exporters in the world, the utilization of the crests of abated animals for the HA obtaining is particularly attractive. The present work sought to extract HA from chicken crest and to determine the molar mass of the extracted acid. Extraction was accomplished by proteolytic digestion with papain during 24 h at 60oC, followed by precipitation with cetylpyridinium chloride (CPC. Hexuronic acid content was determined via the carbazole method, the intrinsic viscosity was measured using the ball viscosimeter, and the molar mass was calculated by extrapolating the calibration line to zero. In addition, qualitative infrared spectroscopy was carried out on the sample using the Bomem MB spectrophotometer. The results show that the extraction method was effective: the extracted acid possesses a large molecular mass, and the extract contains a signifi cant amount of HA.

  15. Evaluating 3D registration of CT-scan images using crest lines

    Science.gov (United States)

    Ayache, Nicholas; Gueziec, Andre P.; Thirion, Jean-Philippe; Gourdon, A.; Knoplioch, Jerome

    1993-06-01

    We consider the issue of matching 3D objects extracted from medical images. We show that crest lines computed on the object surfaces correspond to meaningful anatomical features, and that they are stable with respect to rigid transformations. We present the current chain of algorithmic modules which automatically extract the major crest lines in 3D CT-Scan images, and then use differential invariants on these lines to register together the 3D images with a high precision. The extraction of the crest lines is done by computing up to third order derivatives of the image intensity function with appropriate 3D filtering of the volumetric images, and by the 'marching lines' algorithm. The recovered lines are then approximated by splines curves, to compute at each point a number of differential invariants. Matching is finally performed by a new geometric hashing method. The whole chain is now completely automatic, and provides extremely robust and accurate results, even in the presence of severe occlusions. In this paper, we briefly describe the whole chain of processes, already presented to evaluate the accuracy of the approach on a couple of CT-scan images of a skull containing external markers.

  16. Use of the Vascularized Iliac-Crest Flap in Musculoskeletal Lesions

    Directory of Open Access Journals (Sweden)

    Cristiane Tonoli

    2013-01-01

    Full Text Available Bone loss was in the past treated by several methods, such as bone distraction and the use of nonvascularized or tissue-bank bone grafts. With the advent of modern microsurgical techniques, the vascularized bone flap has been used with good results; it resolves local nutritional problems, repairs soft tissue that is often damaged by severe trauma, and treats bone loss due to tumors, pseudarthroses, and osteomyelitis. This paper reports the authors’ experience with the use of vascularized iliac-crest flaps to treat orthopedic pathologies in five patients with traumatic bone loss (<10 cm, three with osteomyelitis, and three with atrophic nonunion. In all cases, the same surgeon obtained a vascularized iliac-crest flap with a pedicle based on the deep iliac circumflex artery. All flaps consolidated within a mean period of 3 months. These findings demonstrate that the use of an iliac-crest flap is a treatment option in cases of bone loss and that it is associated with good functional results and minimal donor-site morbidity.

  17. Free iliac crest grafts with periosteum for treatment of old acetabular defects

    Institute of Scientific and Technical Information of China (English)

    ZHAO De-wei; SUN Qiang; WANG Ben-jie; CUI Da-ping

    2006-01-01

    Objective: To inquire into the therapeutic effectiveness of free iliac crest grafts with periosteum on old acetabular defects.Methods: From February 1996 to June 2005, 9 patients were treated with free iliac crest grafts with periosteum to reconstruct old acetabular defects. There were 7 males and 2 females and the average age was 41.3 years. The acetabular defects were caused by traffic accidents in 6 cases and fall injury in 3 cases. The time from injury to treatment was 4-13 months and averaged 8 months. Intraoperatively we firstly removed the acetabular fracture fragments of the posterior wall. The femoral head was then reducted. Bone graft was harvested from the iliac crest with periosteum, which was sculpted with a rongeur to conform to the defect. The concave (iliac fossa) side of the graft was placed toward the femoral head. The graft was securedly fixed by two to three leg screws.Results: Postoperative syndrome was not found in any of the cases. Harris' score system showed that the score raised from 32. 3 points preoperatively to 81 points postoperatively. The hip function was evaluated as excellent in 3 cases, good in 4 cases and fair in 2 cases.Conclusions: Although this procedure could not exactly reproduce the anatomy of the hip joint, it enables to restore the posterior stability, provide bone-stock for the hip joints and prevent dislocation of the femoral head.

  18. A NOVEL 3-D MODEL FOR THE WATER CRESTING IN HORIZONTAL WELLS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    In the presence of bottom water, a drop in the reservoir pressure due to fluid production causes the aquifer water to expand and to flow into the reservoir. Therefore, hydrocarbon production from a well is limited by the critical flow rate. The main purpose of this study is to investigate the breakthrough time and the critical rate by using a novel 3-D horizontal well model. Based on the hypothesis that the horizontal well is located in any position of a circular reservoir with no-flow boundary on the top of the reservoir and constant pressure boundary at the bottom, the horizontal well has been regarded as an infinite conductivity line sink and then a 3-D steady-state flow model of the horizontal well is set up. A point sink pressure solution can be obtained with the Fourier transform. The result of the pressure distribution of the uniform flux horizontal well can be presented by means of the principle of superposition. According to the stable water cresting theory, this study confirms the stable height of water cresting and the critical rate. Meanwhile, it can re-confirm the breakthrough time at a specific rate. The output of a comparison between this 3-D model and the reservoir numerical simulator (Eclipse) shows the method presented here can be applied to investigate the behavior of a water cresting and to predict the breakthrough time at the bottom water driver reservoir.

  19. The morphology of the sella turcica in velocardiofacial syndrome suggests involvement of a neural crest developmental field

    DEFF Research Database (Denmark)

    Mølsted, Kirsten; Boers, Maria; Kjaer, Inger

    2010-01-01

    We described the morphology of the sella turcica in individuals with velocardiofacial syndrome (VCFS), also known as chromosome 22q11.2 deletion syndrome, and compared the morphology with that of a control group of individuals from the Oslo University Craniofacial Growth Archive. The aim was to m...

  20. Multipotent Neural Crest Stem Cell-Like Cells from Rat Vibrissa Dermal Papilla Induce Neuronal Differentiation of PC12 Cells

    Directory of Open Access Journals (Sweden)

    Meiying Li

    2014-01-01

    Full Text Available Bone marrow mesenchymal stem cells (BMSCs transplants have been approved for treating central nervous system (CNS injuries and diseases; however, their clinical applications are limited. Here, we model the therapeutic potential of dermal papilla cells (DPCs in vitro. DPCs were isolated from rat vibrissae and characterized by immunocytofluorescence, RT-PCR, and multidifferentiation assays. We examined whether these cells could secrete neurotrophic factors (NTFs by using cocultures of rat pheochromocytoma cells (PC12 with conditioned medium and ELISA assay. DPCs expressed Sox10, P75, Nestin, Sox9, and differentiated into adipocytes, osteoblasts, smooth muscle cells, and neurons under specific inducing conditions. The DPC-conditioned medium (DPC-CM induced neuronal differentiation of PC12 cells and promoted neurite outgrowth. Results of ELISA assay showed that compared to BMSCs, DPCs secreted more brain-derived neurotrophic factor (BDNF and glial cell line-derived neurotrophic factor (GDNF. Moreover, we observed that, compared with the total DPC population, sphere-forming DPCs expressed higher levels of Nestin and P75 and secreted greater amounts of GDNF. The DPCs from craniofacial hair follicle papilla may be a new and promising source for treating CNS injuries and diseases.

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

    OpenAIRE

    Green, Stephen A.; Bronner, Marianne E.

    2014-01-01

    Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen con...

  2. Zebrafish ("Danio rerio") endomembrane antiporter similar to a yeast cation/H(+) transporter is required for neural crest development

    Science.gov (United States)

    CAtion/H (+) eXchangers (CAXs) are integral membrane proteins that transport Ca (2+) or other cations by exchange with protons. While several yeast and plant CAX proteins have been characterized, no functional analysis of a vertebrate CAX homologue has yet been reported. In this study, we further ch...

  3. Minimal-resource computer program for automatic generation of ocean wave ray or crest diagrams in shoaling waters

    Science.gov (United States)

    Poole, L. R.; Lecroy, S. R.; Morris, W. D.

    1977-01-01

    A computer program for studying linear ocean wave refraction is described. The program features random-access modular bathymetry data storage. Three bottom topography approximation techniques are available in the program which provide varying degrees of bathymetry data smoothing. Refraction diagrams are generated automatically and can be displayed graphically in three forms: Ray patterns with specified uniform deepwater ray density, ray patterns with controlled nearshore ray density, or crest patterns constructed by using a cubic polynomial to approximate crest segments between adjacent rays.

  4. Cognitive Remediation and Emotion Skills Training (CREST) for anorexia nervosa in individual format: self-reported outcomes

    OpenAIRE

    Tchanturia, Kate; Doris, Eli; Mountford, Vicki; Fleming, Caroline

    2015-01-01

    Background To evaluate self-reported outcomes after a brief course of skills-based individual therapy for inpatients with anorexia nervosa (AN). Methods In this case series study 37 adults with AN participated in cognitive remediation and emotion skills training (CREST) sessions, and completed social anhedonia, alexithymia and motivational measures before and after the intervention. Results The CREST primary outcome measures were total scores on the Revised Social Anhedonia Scale (RSAS), whic...

  5. The cardiac malpositions.

    Science.gov (United States)

    Perloff, Joseph K

    2011-11-01

    Dextrocardia was known in the 17th century and was 1 of the first congenital malformations of the heart to be recognized. Fifty years elapsed before Matthew Baillie published his account of complete transposition in a human of the thoracic and abdominal viscera to the opposite side from what is natural. In 1858, Thomas Peacock stated that "the heart may be congenitally misplaced in various ways, occupying either an unusual position within the thorax, or being situated external to that cavity." In 1915, Maude Abbott described ectopia cordis, and Richard Paltauf's remarkable illustrations distinguished the various types of dextrocardia. In 1928, the first useful classification of the cardiac malpositions was proposed, and in 1966, Elliott et al's radiologic classification set the stage for clinical recognition. The first section of this review deals with the 3 basic cardiac malpositions in the presence of bilateral asymmetry. The second section deals with cardiac malpositions in the presence of bilateral left-sidedness or right-sidedness. Previous publications on cardiac malpositions are replete with an arcane vocabulary that confounds rather than clarifies. Even if the terms themselves are understood, inherent complexity weighs against clarity. This review was designed as a guided tour of an unfamiliar subject.

  6. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  7. Cardiac effects of vasopressin.

    Science.gov (United States)

    Pelletier, Jean-Sébastien; Dicken, Bryan; Bigam, David; Cheung, Po-Yin

    2014-07-01

    Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits. PMID:24621650

  8. Cardiac potassium channel subtypes

    DEFF Research Database (Denmark)

    Schmitt, Nicole; Grunnet, Morten; Olesen, Søren-Peter

    2014-01-01

    About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K(+) channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K(+) channels...

  9. Cardiac pacemaker power sources

    International Nuclear Information System (INIS)

    A review of chemical and radioisotope batteries used in cardiac pacemakers is presented. The battery systems are examined in terms of longevity, reliability, cost, size and shape, energy density, weight, internal resistance versus time, end-of-life voltage, chemical compatibility, and potential failure mechanisms

  10. Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Sally A. Moody

    2002-01-01

    Full Text Available The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

  11. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

    Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  12. High glucose suppresses embryonic stem cell differentiation into neural lineage cells.

    Science.gov (United States)

    Yang, Penghua; Shen, Wei-bin; Reece, E Albert; Chen, Xi; Yang, Peixin

    2016-04-01

    Abnormal neurogenesis occurs during embryonic development in human diabetic pregnancies and in animal models of diabetic embryopathy. Our previous studies in a mouse model of diabetic embryopathy have implicated that high glucose of maternal diabetes delays neurogenesis in the developing neuroepithelium leading to neural tube defects. However, the underlying process in high glucose-impaired neurogenesis is uncharacterized. Neurogenesis from embryonic stem (ES) cells provides a valuable model for understanding the abnormal neural lineage development under high glucose conditions. ES cells are commonly generated and maintained in high glucose (approximately 25 mM glucose). Here, the mouse ES cell line, E14, was gradually adapted to and maintained in low glucose (5 mM), and became a glucose responsive E14 (GR-E14) line. High glucose induced the endoplasmic reticulum stress marker, CHOP, in GR-E14 cells. Under low glucose conditions, the GR-E14 cells retained their pluripotency and capability to differentiate into neural lineage cells. GR-E14 cell differentiation into neural stem cells (Sox1 and nestin positive cells) was inhibited by high glucose. Neuron (Tuj1 positive cells) and glia (GFAP positive cells) differentiation from GR-E14 cells was also suppressed by high glucose. In addition, high glucose delayed GR-E14 differentiation into neural crest cells by decreasing neural crest markers, paired box 3 (Pax3) and paired box 7 (Pax7). Thus, high glucose impairs ES cell differentiation into neural lineage cells. The low glucose adapted and high glucose responsive GR-E14 cell line is a useful in vitro model for assessing the adverse effect of high glucose on the development of the central nervous system.

  13. Yes-associated protein 65 (YAP expands neural progenitors and regulates Pax3 expression in the neural plate border zone.

    Directory of Open Access Journals (Sweden)

    Stephen T Gee

    Full Text Available Yes-associated protein 65 (YAP contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein. Mouse embryos lacking YAP did not survive past embryonic day 8.5 and showed signs of defective yolk sac vasculogenesis, chorioallantoic fusion, and anterior-posterior (A-P axis elongation. Given that the YAP knockout mouse defects might be due in part to nutritional deficiencies, we sought to better characterize a role for YAP during early development using embryos that develop externally. YAP morpholino (MO-mediated loss-of-function in both frog and fish resulted in incomplete epiboly at gastrulation and impaired axis formation, similar to the mouse phenotype. In frog, germ layer specific genes were expressed, but they were temporally delayed. YAP MO-mediated partial knockdown in frog allowed a shortened axis to form. YAP gain-of-function in Xenopus expanded the progenitor populations in the neural plate (sox2(+ and neural plate border zone (pax3(+, while inhibiting the expression of later markers of tissues derived from the neural plate border zone (neural crest, pre-placodal ectoderm, hatching gland, as well as epidermis and somitic muscle. YAP directly regulates pax3 expression via association with TEAD1 (N-TEF at a highly conserved, previously undescribed, TEAD-binding site within the 5' regulatory region of pax3. Structure/function analyses revealed that the PDZ-binding motif of YAP contributes to the inhibition of epidermal and somitic muscle differentiation, but a complete, intact YAP protein is required for expansion of the neural plate and neural plate border zone progenitor pools. These results provide a thorough analysis of YAP mediated gene expression changes in loss- and gain-of-function experiments. Furthermore, this is the first report to use YAP structure-function analyzes to determine which portion of YAP is involved in specific gene expression changes and the

  14. Auditory stimulation and cardiac autonomic regulation

    Directory of Open Access Journals (Sweden)

    Vitor E. Valenti

    2012-08-01

    Full Text Available Previous studies have already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we described the relationship between musical auditory stimulation and heart rate variability. Searches were performed with the Medline, SciELO, Lilacs and Cochrane databases using the following keywords: "auditory stimulation", "autonomic nervous system", "music" and "heart rate variability". The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Additionally, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasurable songs is involved in cardiac autonomic regulation. Musical auditory stimulation influences heart rate variability through a neural mechanism that is not well understood. Further studies are necessary to develop new therapies to treat cardiovascular disorders.

  15. Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

    2014-09-15

    Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

  16. Sensing and stimulation of the vagus nerve for artificial cardiac control

    NARCIS (Netherlands)

    Ordelman, Simone Cornelia Maria Anna

    2012-01-01

    This thesis focuses on sensing cardiovascular signals from the vagus nerve and electrically stimulating the vagus nerve for cardiovascular effects. Sensing cardiovascular signals was attempted on both spontaneous and evoked neural activity. A cardiac-modulated vagus nerve activity pattern was found

  17. Sudden Cardiac Death

    Directory of Open Access Journals (Sweden)

    Yipsy María Gutiérrez Báez

    2015-09-01

    Full Text Available Since the second half of the twentieth century, dying suddenly due to heart-related problems has become the main health issue in all countries where infectious diseases are not prevalent. Sudden death from cardiac causes is an important global health problem. Major databases were searched for the leading causes of sudden cardiac death. It has been demonstrated that there is a group of hereditary diseases with structural alterations or without apparent organic cause that explains many cases of sudden death in young people, whether related or not to physical exertion. Certain population groups are at higher risk for this disease. They are relatively easy to identify and can be the target of primary prevention measures.

  18. Inherited cardiac disease

    Directory of Open Access Journals (Sweden)

    Philippe Charron

    2012-06-01

    Full Text Available Major advances have been achieved over the two last decades in the field of genetic cardiovascular diseases, not only through increased recognition and understanding of underlying molecular defects but also through rapid translation of knowledge into clinical practice. Genetic counseling and organization of cardiac family screening has become part of the medical management of these diseases, and these should be performed systematically unless an acquired cause has been diagnosed...

  19. Cardiac Tissue Engineering

    OpenAIRE

    MILICA RADISIC; GORDANA VUNJAK-NOVAKOVIC

    2009-01-01

    We hypothesized that clinically sized (1-5 mm thick),compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3) can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of p...

  20. Cardiac developmental toxicity

    OpenAIRE

    Mahler, Gretchen J.; Jonathan T Butcher

    2011-01-01

    Congenital heart disease is a highly prevalent problem with mostly unknown origins. Many cases of CHD likely involve an environmental exposure coupled with genetic susceptibility, but practical and ethical considerations make nongenetic causes of CHD difficult to assess in humans. The development of the heart is highly conserved across all vertebrate species, making animal models an excellent option for screening potential cardiac teratogens. This review will discuss exposures known to cause ...

  1. Cardiac hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-05-15

    Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

  2. Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors.

    Directory of Open Access Journals (Sweden)

    Nathan Salomonis

    2009-11-01

    Full Text Available The role of alternative splicing in self-renewal, pluripotency and tissue lineage specification of human embryonic stem cells (hESCs is largely unknown. To better define these regulatory cues, we modified the H9 hESC line to allow selection of pluripotent hESCs by neomycin resistance and cardiac progenitors by puromycin resistance. Exon-level microarray expression data from undifferentiated hESCs and cardiac and neural precursors were used to identify splice isoforms with cardiac-restricted or common cardiac/neural differentiation expression patterns. Splice events for these groups corresponded to the pathways of cytoskeletal remodeling, RNA splicing, muscle specification, and cell cycle checkpoint control as well as genes with serine/threonine kinase and helicase activity. Using a new program named AltAnalyze (http://www.AltAnalyze.org, we identified novel changes in protein domain and microRNA binding site architecture that were predicted to affect protein function and expression. These included an enrichment of splice isoforms that oppose cell-cycle arrest in hESCs and that promote calcium signaling and cardiac development in cardiac precursors. By combining genome-wide predictions of alternative splicing with new functional annotations, our data suggest potential mechanisms that may influence lineage commitment and hESC maintenance at the level of specific splice isoforms and microRNA regulation.

  3. Population structure and mating system of the Red-crested Korhaan (Lophotis ruficrista) in South Africa

    Institute of Scientific and Technical Information of China (English)

    Johann H van Niekerk

    2015-01-01

    Background:The mating system of the korhaans and bustards in southern Africa is either based on polygyny or monogamy. The Red-crested Korhaan (Lophotis ruficrista) has been described as polygynous but otherwise very little is known about its breeding biology. The aims were to describe the population structure and male behavior during breeding. Methods:The data collected for this paper was mainly based on field transect surveys carried out in 2009, 2010 and 2011. The population structure of the Red-crested Korhaan in the temperate Borakalalo Game Reserve (BGR) was compared with that in the arid Molopo Nature Reserve (MNR) (both situated in the North West province of South Africa). The study was mainly conducted in the BGR but additional work was conducted in the MNR for comparison. Results:The difference in mean group sizes between MNR (1.03) and BGR (1.07) was statistically not significant. Group sizes were not affected by climate despite the fact that the BGR received about 650 mm precipitation per annum and the MNR about 200 mm. In both reserves the apparent sex ratios were skewed in favor of males (1:0.29 in the BGR and 1:0.1 in the MNR). The population was dispersed in a clumped manner which is ascribed to the formation of leks. Leks were positioned in open habitat while females invariably concealed themselves under cover. Conclusions:The leks formed the pivot of the mating system of the Red-crested Korhaan and are identifiable social structures that field ecologists can use to monitor population stability.

  4. Iliac crest allograft glenoid reconstruction for recurrent anterior shoulder instability in athletes: Surgical technique and results

    Directory of Open Access Journals (Sweden)

    Randy Mascarenhas

    2014-01-01

    Full Text Available Performing a labral repair alone in patients with recurrent anterior instability and a large glenoid defect has led to poor outcomes. We present a technique involving the use of the iliac crest allograft inserted into the glenoid defect in athletes with recurrent anterior shoulder instability and large bony defects of the glenoid (>25% of glenoid diameter. All athletes with recurrent anterior shoulder instability and a large glenoid defect that underwent open anterior shoulder stabilization and glenoid reconstruction with the iliac crest allograft were followed over a 4-year period. Preoperatively, a detailed history and physical exam were obtained along with standard radiographs and magnetic resonance imaging of the affected shoulder. All patients also completed the Simple Shoulder Test (SST and American Shoulder and Elbow Surgeons (ASES evaluation forms preoperatively. A computed tomography scan was obtained postoperatively to assess osseous union of the graft and the patient again went through a physical exam in addition to completing the SST, ASES, and Western Ontario Shoulder Instability Index (WOSI forms. 10 patients (9 males, 1 female were followed for an average of 16 months (4-36 months and had a mean age of 24.4 years. All patients exhibited a negative apprehension/relocation test and full shoulder strength at final follow-up. Eight of 10 patients had achieved osseous union at 6 months (80.0%. ASES scores improved from 64.3 to 97.8, and SST scores improved from 66.7 to 100. Average postoperative WOSI scores were 93.8%. The use of the iliac crest allograft provides a safe and clinically useful alternative compared to previously described procedures for recurrent shoulder instability in the face of glenoid deficiency.

  5. Estimating viability and sensitivity of the great crested newt Triturus cristatus at a regional scale

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    J. C. Malmgren

    2007-09-01

    Full Text Available Viability and sensitivity of the great crested newt Triturus cristatus were simulated under different scenarios with a demographically and spatially structured stochastic model in an area of 144 km2 in southeastern Sweden. Eighteen ponds were monitored using drift fences with pitfall traps, funnel traps, visual observation and netting during the spring and summer of 2004. Estimated adult population sizes ranged between 0 and 620 individuals and the mean (±SD local population size was 297 ± 233 individuals. Due to uncertainty of the data, the model was simulated with parameter ranges to estimate upper and lower bounds of viability. Estimated quasi-extinction risk (the risk of each population in the study area falling below 10 females within a 50-yr period ranged from 100% to 0%, with a “best” estimate of 19.2%. The parameter most sensitive for the model outcome was fecundity, followed by juvenile survival, adult survival and transition from juvenile to adult. When these parameters were set at their lower bound, the quasi-extinction risk increased to 80–100%, while simulating these parameters at their higher bound inferred no or nearly no risk of quasi-extinction. This highlights the importance of focusing conservation efforts and research on the early life cycle stages. Management measures such as restoration of ponds and increased pond density decreased the risk for the great crested newt to end up quasi-extinct in the study area after 50 yr. The results may have implications on management measures of great crested newts throughout its distribution area.

  6. The Crest of the Peacock Non-European Roots of Mathematics (Third Edition)

    CERN Document Server

    Joseph, George Gheverghese

    2011-01-01

    From the Ishango Bone of central Africa and the Inca quipu of South America to the dawn of modern mathematics, The Crest of the Peacock makes it clear that human beings everywhere have been capable of advanced and innovative mathematical thinking. George Gheverghese Joseph takes us on a breathtaking multicultural tour of the roots and shoots of non-European mathematics. He shows us the deep influence that the Egyptians and Babylonians had on the Greeks, the Arabs' major creative contributions, and the astounding range of successes of the great civilizations of India and China. The third editio

  7. 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...... demonstrates a reasonably similar evolution. These simulations consider the simplest physical situations involving three-dimensional instabilities of genuinely three-dimensional progressive waves, revealing qualitative differences from classical two-dimensional descriptions. This study is therefore...

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

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2006-01-01

    A numerical study of quasi-steady, doubly-periodic monochromatic short-crested wave patterns in deep water is conducted using a high-order Boussinesq-type model. Simulations using linear wavemaker conditions in the nonlinear model are initially used to approximate conditions from recent laboratory...... inclusion of steady third-order components in the wave generation is shown to significantly reduce the modulations (and other unsteady features), further confirming the explanation. This numerical work makes apparent some previously unknown difficulties associated with the physical generation of even...

  9. An archaic crested plesiosaur in opal from the Lower Cretaceous high-latitude deposits of Australia

    OpenAIRE

    Kear, Benjamin P.; Schroeder, Natalie I; Michael S Y Lee

    2006-01-01

    Umoonasaurus demoscyllus gen. et sp. nov. is a new small-bodied (approx. 2.5 m) pliosauroid plesiosaur from the Lower Cretaceous (Aptian–Albian) of southern Australia. It is represented by several partial skeletons (one with a near complete skull is the most complete opalized vertebrate fossil yet known), and is unique in having large crests on the skull midline and above the orbits. Umoonasaurus is surprisingly archaic despite its relatively late age (approx. 115 Myr ago)—being simultaneousl...

  10. Reconstruction of iliac crest with rib to prevent donor site complications: A prospective study of 26 cases

    Directory of Open Access Journals (Sweden)

    Dave B

    2007-01-01

    Full Text Available Background: The tricortical bone graft from the iliac crest are used to reconstruct the post corpectomy spinal defects. The donor iliac area defect is large and may give rise to pain at donor site, instability of pelvis, fracture of ilium, donor site muscle herniation or abdominal content herniation. Rib removed during thoracotomy was used by us to reconstruct the iliac crest defect. Materials and Methods: Twenty-six patients who underwent thoracotomy for dorsal spine corpectomy or curettage for various spinal pathologies from June 2002 to May 2004 were included in the study. After adequate decompression the spine was reconstructed by tricortical bone graft from iliac crest and reconstruction of the iliac crest was done with the rib removed for exposure during thoracotomy. Results: The mean follow up was 15 months. All patients had good graft incorporation which was evaluated on the basis of local tenderness and radiographs. One patient had graft displacement. Conclusion: The reconstruction of iliac crest by rib is a simple and effective procedure to prevent donor site complications.

  11. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng

    2007-01-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  12. An overview of cardiac morphogenesis.

    Science.gov (United States)

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  13. Sudden Cardiac Death in Athletes.

    Science.gov (United States)

    Wasfy, Meagan M; Hutter, Adolph M; Weiner, Rory B

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  14. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    changes or to abandon the strong identity thesis altogether. Were one to pursue a theory according to which consciousness is not an epiphenomenon to brain processes, consciousness may in fact affect its own neural basis. The neural correlate of consciousness is often seen as a stable structure, that is......In contemporary consciousness studies the phenomenon of neural plasticity has received little attention despite the fact that neural plasticity is of still increased interest in neuroscience. We will, however, argue that neural plasticity could be of great importance to consciousness studies....... If consciousness is related to neural processes it seems, at least prima facie, that the ability of the neural structures to change should be reflected in a theory of this relationship "Neural plasticity" refers to the fact that the brain can change due to its own activity. The brain is not static but rather...

  15. Neural Tube Defects

    Science.gov (United States)

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

  16. Morphological neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Ritter, G.X.; Sussner, P. [Univ. of Florida, Gainesville, FL (United States)

    1996-12-31

    The theory of artificial neural networks has been successfully applied to a wide variety of pattern recognition problems. In this theory, the first step in computing the next state of a neuron or in performing the next layer neural network computation involves the linear operation of multiplying neural values by their synaptic strengths and adding the results. Thresholding usually follows the linear operation in order to provide for nonlinearity of the network. In this paper we introduce a novel class of neural networks, called morphological neural networks, in which the operations of multiplication and addition are replaced by addition and maximum (or minimum), respectively. By taking the maximum (or minimum) of sums instead of the sum of products, morphological network computation is nonlinear before thresholding. As a consequence, the properties of morphological neural networks are drastically different than those of traditional neural network models. In this paper we consider some of these differences and provide some particular examples of morphological neural network.

  17. Case Report: Penetrating Cardiac Injury

    Directory of Open Access Journals (Sweden)

    Adem Grbolar

    2013-10-01

    Full Text Available Summary: Penetrating cardiac injurys caused by gunshots and penetrating tools have high mortality rates. The way of injury, how the cardiac area is effected and the presence of cardiac tamponadecauses mortality in different rates. However the better treatment quality of hospitals, increasingoperative techniques, and internel care unit quality has not been change during the years. Searching the literature, we want to present a 42 years old male patient whowas injured by knife and had a 1 cm skin wound on chest with cardiac tamponade. After sternotomy a 7 cm laseration was observed in heart. Cardioraphy was performed.

  18. Artificial neural interfaces for bionic cardiovascular treatments.

    Science.gov (United States)

    Kawada, Toru; Sugimachi, Masaru

    2009-01-01

    An artificial nerve, in the broad sense, may be conceptualized as a physical and logical interface system that reestablishes the information traffic between the central nervous system and peripheral organs. Studies on artificial nerves targeting the autonomic nervous system are in progress to explore new treatment strategies for several cardiovascular diseases. In this article, we will review our research targeting the autonomic nervous system to treat cardiovascular diseases. First, we identified the rule for decoding native sympathetic nerve activity into a heart rate using transfer function analysis, and established a framework for a neurally regulated cardiac pacemaker. Second, we designed a bionic baroreflex system to restore the baroreflex buffering function using electrical stimulation of the celiac ganglion in a rat model of orthostatic hypotension. Third, based on the hypothesis that autonomic imbalance aggravates chronic heart failure, we implanted a neural interface into the right vagal nerve and demonstrated that intermittent vagal stimulation significantly improved the survival rate in rats with chronic heart failure following myocardial infarction. Although several practical problems need to be resolved, such as those relating to the development of electrodes feasible for long-term nerve activity recording, studies of artificial neural interfaces with the autonomic nervous system have great possibilities in the field of cardiovascular treatment. We expect further development of artificial neural interfaces as novel strategies to cope with cardiovascular diseases resistant to conventional therapeutics.

  19. Holographic neural networks

    OpenAIRE

    Manger, R

    1998-01-01

    Holographic neural networks are a new and promising type of artificial neural networks. This article gives an overview of the holographic neural technology and its possibilities. The theoretical principles of holographic networks are first reviewed. Then, some other papers are presented, where holographic networks have been applied or experimentally evaluated. A case study dealing with currency exchange rate prediction is described in more detail.

  20. Neural tissue-spheres

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Johansen, Mathias; Blaabjerg, Morten;

    2007-01-01

    By combining new and established protocols we have developed a procedure for isolation and propagation of neural precursor cells from the forebrain subventricular zone (SVZ) of newborn rats. Small tissue blocks of the SVZ were dissected and propagated en bloc as free-floating neural tissue...... content, thus allowing experimental studies of neural precursor cells and their niche...

  1. READING A NEURAL CODE

    NARCIS (Netherlands)

    BIALEK, W; RIEKE, F; VANSTEVENINCK, RRD; WARLAND, D

    1991-01-01

    Traditional approaches to neural coding characterize the encoding of known stimuli in average neural responses. Organisms face nearly the opposite task - extracting information about an unknown time-dependent stimulus from short segments of a spike train. Here the neural code was characterized from

  2. Validation of MRI measurement of cardiac output in the dog: the effects of dobutamine and minoxidil.

    Science.gov (United States)

    Hockings, Paul D; Busza, Albert L; Byrne, Joanne; Patel, Bela; Smart, Sean C; Reid, David G; Lloyd, Heather L; White, Alan; Pointing, Karen; Farnfield, Belinda A; Criado-Gonzalez, Ana; Whelan, Greg A; Taylor, Gemma L; Birmingham, Jeffrey M; Slaughter, Mark R; Osborne, Janette A; Krebs-Brown, Axel; Templeton, David

    2003-01-01

    The use of magnetic resonance imaging (MRI) for the measurement of cardiac output parameters in anesthetized adult male beagle dogs has been validated against a widely accepted thermodilution method. Using a multislice cine gradient echo MRI method to acquire images of the entire heart, left ventricular lumen volumes were measured at systole and diastole in seven animals. Cardiac output correlated well (R 2 = 0.88) with thermodilution measurements made in a parallel manner, both before and during acute stimulation with the inotrope dobutamine. In a chronic study of changes in cardiac morphology and function brought about by the antihypertensive minoxidil, MRI reliably detected the expected increases in stroke volume (28%) and cardiac output (58%) resulting from neural reaction to decreased blood pressure. Left ventricular lumen enlarged as well in response to fluid retention and plasma volume increase. Two in four minoxidil-treated animals also developed clear MRI-visible pericardial effusion. PMID:20021181

  3. Theoretical Investigation of Peak-Delay Force Reduction for Caissons Exposed to Non-breaking Short-Crested Waves

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Liu, Z.

    In nature coastal structures are exposed to oblique short-crested waves. The effect of wave incident angle on total wave force on a long caisson are twofold. The one is the force reduction due to the reduction of instantaneous point pressure on the caisson, named point-pressure force reduction....... The other is the force reduction due to the fact that the peak pressures do not occur simultaneously along the caisson, named peak-delay force reduction. These two reduction effects can also be expected with short-crested waves, as the short-crestedness of waves means the spreading of wave energy over...... on the peak-delay force reduction of caissons exposed to non-breaking short-crested waves. Battjes (1982) has investigated theoretically the peak-delay force reduction of shortcrested waves with only one frequency component. Such a force reduction factor cannot be applied because in nature waves are composed...

  4. Misexpression of Pknox2 in mouse limb bud mesenchyme perturbs zeugopod development and deltoid crest formation.

    Science.gov (United States)

    Zhou, Wenrong; Zhu, Huang; Zhao, Jianzhi; Li, Hanjun; Wan, Yong; Cao, Jingjing; Zhao, Haixia; Yu, Jian; Zhou, Rujiang; Yao, Yiyun; Zhang, Lingling; Wang, Lifang; He, Lin; Ma, Gang; Yao, Zhengju; Guo, Xizhi

    2013-01-01

    The TALE (Three Amino acid Loop Extension) family consisting of Meis, Pbx and Pknox proteins is a group of transcriptional co-factors with atypical homeodomains that play pivotal roles in limb development. Compared to the in-depth investigations of Meis and Pbx protein functions, the role of Pknox2 in limb development remains unclear. Here, we showed that Pknox2 was mainly expressed in the zeugopod domain of the murine limb at E10.5 and E11.5. Misexpression of Pknox2 in the limb bud mesenchyme of transgenic mice led to deformities in the zeugopod and forelimb stylopod deltoid crest, but left the autopod and other stylopod skeletons largely intact. These malformations in zeugopod skeletons were recapitulated in mice overexpressing Pknox2 in osteochondroprogenitor cells. Molecular and cellular analyses indicated that the misexpression of Pknox2 in limb bud mesenchyme perturbed the Hox10-11 gene expression profiles, decreased Col2 expression and Bmp/Smad signaling activity in the limb. These results indicated that Pknox2 misexpression affected mesenchymal condensation and early chondrogenic differentiation in the zeugopod skeletons of transgenic embryos, suggesting Pknox2 as a potential regulator of zeugopod and deltoid crest formation. PMID:23717575

  5. Misexpression of Pknox2 in mouse limb bud mesenchyme perturbs zeugopod development and deltoid crest formation.

    Directory of Open Access Journals (Sweden)

    Wenrong Zhou

    Full Text Available The TALE (Three Amino acid Loop Extension family consisting of Meis, Pbx and Pknox proteins is a group of transcriptional co-factors with atypical homeodomains that play pivotal roles in limb development. Compared to the in-depth investigations of Meis and Pbx protein functions, the role of Pknox2 in limb development remains unclear. Here, we showed that Pknox2 was mainly expressed in the zeugopod domain of the murine limb at E10.5 and E11.5. Misexpression of Pknox2 in the limb bud mesenchyme of transgenic mice led to deformities in the zeugopod and forelimb stylopod deltoid crest, but left the autopod and other stylopod skeletons largely intact. These malformations in zeugopod skeletons were recapitulated in mice overexpressing Pknox2 in osteochondroprogenitor cells. Molecular and cellular analyses indicated that the misexpression of Pknox2 in limb bud mesenchyme perturbed the Hox10-11 gene expression profiles, decreased Col2 expression and Bmp/Smad signaling activity in the limb. These results indicated that Pknox2 misexpression affected mesenchymal condensation and early chondrogenic differentiation in the zeugopod skeletons of transgenic embryos, suggesting Pknox2 as a potential regulator of zeugopod and deltoid crest formation.

  6. 3D laboratory experiments on a system of low-crested breakwaters under oblique wave attack

    Science.gov (United States)

    Papacharalampous, Georgia; Karantinos, Michalis; Giantsi, Theodora; Moutzouris, Constantinos

    2016-04-01

    Low-crested breakwaters are being increasingly used for shore protection. Hydrodynamics around coastal structures are complicated and have not been fully understood. A series of large scale (1:40) 3D laboratory experiments were carried out in the Laboratory of Harbour Works, National Technical University of Athens to investigate the wave disturbance around a system of two non-parallel to the shoreline breakwaters. The structures were of the type of low-crested, permeable and attacked by obliquely incident waves. Three different water depths were tested in the basin with a range of various different spectra. The transmission and reflection coefficients were measured in the middle of each breakwater. For this purpose, 1 gauge and 4 gauges (in line) were placed on the landward and seaward side of each breakwater respectively. The effect of diffraction is incorporate at the measured wave heights. The measured coefficients are being compared to their corresponding estimated using existing empirical formulas. Most of those formulas neglect wave obliquity.

  7. Modelling shock to detonation transition in PETN using HERMES and CREST

    Science.gov (United States)

    Maheswaran, Mary-Ann; Curtis, John; Reaugh, Jack

    2013-06-01

    The High Explosive Response to MEchanical Stimulus (HERMES) model has been developed to address High Explosive Violent Response (HEVR). It is a material model for use in the both the LS-DYNA finite element and ALE3D hydrocodes that enables the modelling of both shock to detonation (SDT) and deflagration to detonation (DDT) transition. As part of its ongoing development and application, model parameters for the explosive PETN were found by using experimental data for PETN at different densities. PETN was selected because of the availability of both SDT and DDT data. To model SDT and DDT, HERMES uses a subset of the CREST reactive burn model with the Mie-Gruneisen equation of state (EOS) for the unreacted explosive and a look-up table for the gas EOS as generated by Cheetah. The unreacted EOS parameters were found first by calculating the principal isentrope of unreacted PETN at TMD from PETN shock Hugoniot data. Then Pop-plot data for PETN was used to fit the CREST parameters at each density. The resulting new PETN HERMES material model provides a platform for further investigations of SDT and DDT in low density PETN powder. JER's activity was performed under the auspices of the US DOE by LLNL under Contract DE-AC52-07NA27344, and partially funded by the Joint US DoD/DOE Munitions Technology Development Program.

  8. Ascaris spp. and Capillaria caudinflata infections in captive-bred crested ibis (Nipponia nippon) in China.

    Science.gov (United States)

    Zhang, Xu; Qiao, Ji Ying; Wu, Xiao Min; Ma, Qing Yi; Hu, Han; Wang, Jing; Che, Li Feng

    2015-01-01

    Crested ibis (Nipponia nippon), an endan gered native bird, was called the "precious stone" of oriental birds. N. nippon was considered a critically endangered species in the IUCN Red List of Threatened Species and a first-class national protected animal in China. The Chinese government had exerted considerable effort to protect the N. nippon population. An effective approach to increase the number of these birds was captive breeding. However, several pathogens, including parasites, could jeopardize the health of this species. The present study used the fecal flotation method to determine prevalence of intestinal parasites in fresh stool samples by wet mount smearing and iodine staining. Samples were obtained from 63 randomly selected crested ibis bred in Shaanxi Rare Wildlife Rescuing and Breeding Research Center in Zhouzhi County, Xi'an City, Shaanxi Province, China. In the 63 captive individuals, 38 were found positive for intestinal parasites (60.3%, 38/63). Of positive birds, high prevalence of Ascaris spp. (84.2%, 32/38) and Capillaria caudinflata (50.0%, 19/38) were detected. Coccidea (7.8%, 3/38), Fasciolidae (23.7%, 9/38), Blastocystis spp. (15.8%, 6/38), and Entamoeba histolytica (7.8%, 3/38) showed relatively low prevalence rates. This study focuses on the morphological identification of Ascaris spp. and C. caudinflata and their transmission in the N. nippon population. We introduce strategies to improve the breeding management of the birds, enhance their health, and stimulate population productivity. PMID:25486916

  9. Antifibrinolytics in cardiac surgery

    Directory of Open Access Journals (Sweden)

    Achal Dhir

    2013-01-01

    Full Text Available Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA or epsilon amino caproic acid (EACA. While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

  10. Cardiac and vascular changes in cirrhosis: Pathogenic mechanisms

    Institute of Scientific and Technical Information of China (English)

    HongQun Liu; Seyed Ali Gaskari; Samuel S Lee

    2006-01-01

    Cardiovascular abnormalities accompany both portal hypertension and cirrhosis. These consist of hyperdynamic circulation, defined as reduced mean arterial pressure and systemic vascular resistance, and increased cardiac output. Despite the baseline increased cardiac output,ventricular inotropic and chronotropic responses to stimuli are blunted, a condition known as cirrhotic cardiomyopathy. Both conditions may play an initiating or aggravating pathogenic role in many of the complications of liver failure or portal hypertension including ascites,variceal bleeding, hepatorenal syndrome and increased postoperative mortality after major surgery or liver transplantation. This review briefly examines the major mechanisms that may underlie these cardiovascular abnormalities, concentrating on nitric oxide, endogenous cannabinoids, central neural activation and adrenergic receptor changes. Future work should address the complex interrelationships between these systems.

  11. Cardiac MR image segmentation using CHNN and level set method

    Institute of Scientific and Technical Information of China (English)

    王洪元; 周则明; 王平安; 夏德深

    2004-01-01

    Although cardiac magnetic resonance imaging (MRI) can provide high spatial resolution image, the area gray level inhomogenization, weak boundary and artifact often can be found in MR images. So, the MR images segmentation using the gradient-based methods is poor in quality and efficiency. An algorithm, based on the competitive hopfield neural network (CHNN) and the curve propagation, is proposed for cardiac MR images segmentation in this paper. The algorithm is composed of two phases. In first phase, a CHNN is used to classify the image objects, and to make gray level homogenization and to recognize weak boundaries in objects. In second phase, based on the classified results, the level set velocity function is created and the object boundaries are extracted with the curve propagation algorithm of the narrow band-based level set. The test results are promising and encouraging.

  12. The patterns of surface capillary-gravity short-crested waves with uniform current fields in coastal waters

    Institute of Scientific and Technical Information of China (English)

    Hu Huang; Jia Fu

    2006-01-01

    A fully three-dimensional surface gravitycapillary short-crested wave system is studied as two progressive wave-trains of equal amplitude and frequency, which are collinear with uniform currents and doubly-periodic in the horizontal plane, are propagating at an angle to each other. The first-and second-order asymptotic analytical solutions of the short-crested wave system are obtained via a perturbation expansion in a small parameter associated with the wave steepness, therefore depicting a series of typical three-dimensional wave patterns involving currents, shallow and deep water, and surface capillary waves, and comparing them with each other.

  13. Cardiac arrest – cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Basri Lenjani

    2014-01-01

    Conclusions: All survivors from cardiac arrest have received appropriate medical assistance within 10 min from attack, which implies that if cardiac arrest occurs near an institution health care (with an opportunity to provide the emergent health care the rate of survival is higher.

  14. Leadership in cardiac surgery.

    Science.gov (United States)

    Rao, Christopher; Patel, Vanash; Ibrahim, Michael; Ahmed, Kamran; Wong, Kathie A; Darzi, Ara; von Segesser, Ludwig K; Athanasiou, Thanos

    2011-06-01

    Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importance. PMID:20884217

  15. Interventional cardiac catheterization.

    Science.gov (United States)

    Pihkala, J; Nykanen, D; Freedom, R M; Benson, L N

    1999-04-01

    Over the past decade, transcatheter interventions have become increasingly important in the treatment of patients with congenital heart lesions. These procedures may be broadly grouped as dilations (e.g., septostomy, valvuloplasty, angioplasty, and endovascular stenting) or as closures (e.g., vascular embolization and device closure of defects). Balloon valvuloplasty has become the treatment of choice for patients in all age groups with simple valvar pulmonic stenosis and, although not curative, seems at least comparable to surgery for congenital aortic stenosis in newborns to young adults. Balloon angioplasty is successfully applied to a wide range of aortic, pulmonary artery, and venous stenoses. Stents are useful in dilating lesions of which the intrinsic elasticity results in vessel recoil after balloon dilation alone. Catheter-delivered coils are used to embolize a wide range of arterial, venous, and prosthetic vascular connections. Although some devices remain investigational, they have been successfully used for closure of many arterial ducts and atrial and ventricular septal defects. In the therapy for patients with complex CHD, best results may be achieved by combining cardiac surgery with interventional catheterization. The cooperation among interventional cardiologists and cardiac surgeons was highlighted in a report of an algorithm to manage patients with tetralogy of Fallot or pulmonary atresia with diminutive pulmonary arteries, involving balloon dilation, coil embolization of collaterals, and intraoperative stent placement. In this setting, well-planned catheterization procedures have an important role in reducing the overall number of procedures that patients may require over a lifetime, with improved outcomes.

  16. Ictal Cardiac Ryhthym Abnormalities.

    Science.gov (United States)

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  17. Pneumothorax in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nohr, Ellen Aagaard;

    2012-01-01

    AIM: To identify risk factors for pneumothorax treated with a chest tube after cardiac pacing device implantation in a population-based cohort.METHODS AND RESULTS: A nationwide cohort study was performed based on data on 28 860 patients from the Danish Pacemaker Register, which included all Danish...... patients who received their first pacemaker (PM) or cardiac resynchronization device from 1997 to 2008. Multiple logistic regression was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for the association between risk factors and pneumothorax treated with a chest tube. The median...... age was 77 years (25th and 75th percentile: 69-84) and 55% were male (n = 15 785). A total of 190 patients (0.66%) were treated for pneumothorax, which was more often in women [aOR 1.9 (1.4-2.6)], and in patients with age >80 years [aOR 1.4 (1.0-1.9)], a prior history of chronic obstructive pulmonary...

  18. Automatic Classification of Heartbeats Using Wavelet Neural Network

    OpenAIRE

    BENALI, Radhwane; Bereksi-Reguig, Fethi; HADJ SLIMANE, Zinedine

    2012-01-01

    The electrocardiogram (ECG) signal is widely employed as one of the most important tools in clinical practice in order to assess the cardiac status of patients. The classification of the ECG into different pathologic disease categories is a complex pattern recognition task. In this paper, we propose a method for ECG heartbeat pattern recognition using wavelet neural network (WNN). To achieve this objective, an algorithm for QRS detection is first implemented, then a WN...

  19. Affect intensity and cardiac arousal.

    Science.gov (United States)

    Blascovich, J; Brennan, K; Tomaka, J; Kelsey, R M; Hughes, P; Coad, M L; Adlin, R

    1992-07-01

    Relationships between affect intensity and basal, evoked, and perceived cardiac arousal were investigated in 3 experiments. Affect intensity was assessed using Larsen and Diener's (1987) Affect Intensity Measure (AIM). Cardiac arousal was evoked with exercise in the 1st study and with mental arithmetic in the 2nd and 3rd. Perceived cardiac arousal was measured under optimal conditions using a standard heartbeat discrimination procedure. Women as a group scored higher on the AIM. Affect intensity was unrelated to basal or evoked cardiac arousal and was negatively related to perceived cardiac arousal in all 3 studies. Data suggest that affect intensity, although unrelated to actual physiological arousal, is negatively related to the accuracy with which individuals perceive their own arousal. Results are discussed within the context of an expanded arousal-regulation model (Blascovich, 1990). PMID:1494983

  20. Chaotic diagonal recurrent neural network

    Institute of Scientific and Technical Information of China (English)

    Wang Xing-Yuan; Zhang Yi

    2012-01-01

    We propose a novel neural network based on a diagonal recurrent neural network and chaos,and its structure andlearning algorithm are designed.The multilayer feedforward neural network,diagonal recurrent neural network,and chaotic diagonal recurrent neural network are used to approach the cubic symmetry map.The simulation results show that the approximation capability of the chaotic diagonal recurrent neural network is better than the other two neural networks.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-01

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

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

    International Nuclear Information System (INIS)

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

  3. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

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

  4. Genomic signatures of near-extinction and rebirth of the crested ibis and other endangered bird species

    DEFF Research Database (Denmark)

    Li, Shengbin; Li, Bo; Cheng, Cheng;

    2014-01-01

    -East Asia, by 1981 only seven individuals from two breeding pairs remained in the wild. The recovering crested ibis populations thus provide an excellent example for conservation genomics since every individual bird has been recruited for genomic and demographic studies.ResultsUsing high-quality genome...

  5. Single-blinded prospective randomized study comparing open versus needle technique for obtaining autologous cancellous bone from the iliac crest.

    NARCIS (Netherlands)

    Bartels, R.H.M.A.

    2005-01-01

    One of the most frequent complications of cervical anterior discectomy with fusion is pain at the donor site, usually the iliac crest. Despite the advent of new materials, autologous bone is still the "gold standard" for fusion procedures. A prospective, single blinded, randomized study was performe

  6. Cryptic crested newt diversity at the Eurasian transition: the mitochondrial DNA phylogeography of Near Eastern Triturus newts.

    Science.gov (United States)

    Wielstra, B; Themudo, G Espregueira; Güçlü, O; Olgun, K; Poyarkov, N A; Arntzen, J W

    2010-09-01

    Crested newts of the Triturus karelinii group occur in a phylogeographically understudied region: the Near East. Controversy surrounds the systematic position of these newts within the complete crested newt assemblage (the Triturus cristatus superspecies). We explore the situation using mitochondrial sequence data (ND2 and ND4, approximately 1.7kb) and employing different methods of phylogenetic inference (Bayesian inference and Maximum Likelihood using mixed models) and molecular dating (r8s and BEAST). The T. karelinii group is monophyletic and constitutes one of four main lineages in the T. cristatus superspecies. The separation of the T. karelinii group from the remaining crested newts around 9Ma is related to the formation of the Mid-Aegean Trench, which separated the Balkan and Anatolian landmasses. The T. karelinii group comprises three geographically structured clades (eastern, central and western). The genetic divergence shown by these clades is comparable to that among recognized crested newt species. We suggest the uplift of the Armenian Plateau to be responsible for the separation of the eastern clade around 7Ma, and the re-establishment of a marine connection between the Black Sea and the Mediterranean at the end of the Messinian Salinity Crisis to have caused the split between the central and western clade around 5.5Ma. Genetic structuring within the three clades dates to the Quaternary Ice Age (<2.59Ma) and is associated with alternating periods of isolation and reconnection caused by periodic changes in sea level and surface runoff. PMID:20435147

  7. The effect of a single dose of bupivacaine on donor site pain after anterior iliac crest bone harvesting.

    NARCIS (Netherlands)

    Barkhuysen, R.; Meijer, G.J.; Soehardi, A.; Merkx, M.A.W.; Borstlap, W.A.; Berge, S.J.; Bronkhorst, E.M.; Hoppenreijs, T.J.M.

    2010-01-01

    Transplants from the anterior iliac crest are used for most reconstructive procedures in cranio-maxillofacial surgery. The advantages are easy accessibility, the ability to work in two teams and the amount of corticocancellous bone available; disadvantages are postoperative pain and gait disturbance

  8. Prenuptial perfume: Alloanointing in the social rituals of the crested auklet ( Aethia cristatella) and the transfer of arthropod deterrents

    Science.gov (United States)

    Douglas, Hector D.

    2008-01-01

    Alloanointing, the transfer of chemicals between conspecifics, is known among mammals, but hitherto, the behavior has not been documented for birds. The crested auklet ( Aethia cristatella), a colonial seabird of Alaskan and Siberian waters, alloanoints during courtship with fragrant aldehydes that are released from specialized wick-like feathers located in the interscapular region. Crested auklets solicit anointment at the colony, and prospective mates rub bill, breast, head, and neck over wick feathers of their partners. This distributes aldehydes over the head, neck, and face where the birds cannot self-preen. The resulting chemical concentrations are sufficient to deter ectoparasites. Auklets that emit more odorant can transfer more defensive chemicals to mates and are thus more sexually attractive. Behavioral studies showed that crested auklets are attracted to their scent. Wild birds searched for dispensers that emitted their scent and rubbed their bills on the dispensers and engaged in vigorous anointment behaviors. In captive experiments, naïve crested auklets responded more strongly to synthetic auklet scent than controls, and the greatest behavioral response occurred during early courtship. This study extends scientific knowledge regarding functions of alloanointing. Alloanointing had previously been attributed to scent marking and individual recognition in vertebrates. Alloanointing is described here in the context of an adaptive social cue — the transfer of arthropod deterrents between prospective mates.

  9. Morphodynamic responds of groyne fields to the lowering of crest level of the groynes in the Waal River, The Netherlands

    NARCIS (Netherlands)

    Busnelli, M.M.; Schuurman, F.; Sieben, A.; Wal, Maarten van der; Hector, H.

    2011-01-01

    The lowering of the crest of the groynes in the River Waal is one of the measures being applied in the Netherlands to reduce the water levels at high water conditions. A total of 750 groynes will be lowered lengthwise by 1 to 2 meters. An expected side-effect is sedimentation in the main channel, du

  10. A Phenotypic Point of View of the Adaptive Radiation of Crested Newts (Triturus cristatus Superspecies, Caudata, Amphibia

    Directory of Open Access Journals (Sweden)

    Ana Ivanović

    2012-01-01

    Full Text Available The divergence in phenotype and habitat preference within the crested newt Triturus cristatus superspecies, examined across different ontogenetic stages, provides an excellent setting to explore the pattern of adaptive radiation. The crested newts form a well-supported monophyletic clade for which at least the full mitochondrial DNA phylogeny is resolved. Here we summarise studies that explored the variation in morphological (larval and adult body form, limb skeleton, and skull shape and other phenotypic traits (early life history, developmental sequences, larval growth rate, and sexual dimorphism to infer the magnitude and direction of evolutionary changes in crested newts. The phenotypic traits show a high level of concordance in the pattern of variation; there is a cline-like variation, from T. dobrogicus, via T. cristatus, T. carnifex, and T. macedonicus to the T. karelinii group. This pattern matches the cline of ecological preferences; T. dobrogicus is relatively aquatic, followed by T. cristatus. T. macedonicus, T. carnifex, and the T. karelinii group are relatively terrestrial. The observed pattern indicates that phenotypic diversification in crested newts emerged due to an evolutionary switch in ecological preferences. Furthermore, the pattern indicates that heterochronic changes, or changes in the timing and rate of development, underlie the observed phenotypic evolutionary diversification.

  11. Physics of Cardiac Arrhythmogenesis

    Science.gov (United States)

    Karma, Alain

    2013-04-01

    A normal heartbeat is orchestrated by the stable propagation of an excitation wave that produces an orderly contraction. In contrast, wave turbulence in the ventricles, clinically known as ventricular fibrillation (VF), stops the heart from pumping and is lethal without prompt defibrillation. I review experimental, computational, and theoretical studies that have shed light on complex dynamical phenomena linked to the initiation, maintenance, and control of wave turbulence. I first discuss advances made to understand the precursor state to a reentrant arrhythmia where the refractory period of cardiac tissue becomes spatiotemporally disordered; this is known as an arrhythmogenic tissue substrate. I describe observed patterns of transmembrane voltage and intracellular calcium signaling that can contribute to this substrate, and symmetry breaking instabilities to explain their formation. I then survey mechanisms of wave turbulence and discuss novel methods that exploit electrical pacing stimuli to control precursor patterns and low-energy pulsed electric fields to control turbulence.

  12. Crest Factor Reduction in MC-CDMA Employing Carrier Interferometry Codes

    Directory of Open Access Journals (Sweden)

    Natarajan Balasubramaniam

    2004-01-01

    Full Text Available This paper addresses signal compactness issues in MC-CDMA employing carrier interferometry codes using the measure of crest factor (CF. Carrier interferometry codes, applied to N -carrier MC-CDMA systems, enable 2N users to simultaneously share the system bandwidth with minimal degradation in performance (relative to the N -orthogonal-user case. First, for a fully loaded ( K=N and K=2N users MC-CDMA system with practical values of N , it is shown that the CF in downlink transmission demonstrates desirable properties of low mean and low variance. The downlink CF degrades when the number of users in the system decreases. Next, the high CF observed in the uplink is characterized and the poor CF in a partially loaded downlink as well as uplink is effectively combated using Schroeder's analytical CF reduction techniques.

  13. Head Discharge Relationship of Thin Plated Rectangular Lab Fabricated Sharp Crested Weirs

    Directory of Open Access Journals (Sweden)

    S. A. Tekade

    2016-01-01

    Full Text Available Measuring open channel flows has been a major challenge at the field level. Because of the fact that the measuring devices are to be made from procedures and materials prescribed in standard codes. Weirs over a period of time had been used to measure discharges in open channel systems. But non-availability of standard material at village level proves to be a major bottleneck in implementing weirs as field measurement devices. The present experimental study is an attempt to prove the good hydraulic performance of weirs made of locally available metal sheets. That use of complicated material and machining is not necessary in the fabrication of rectangular weir. A discharge formula for the rectangular weir of different sizes is extensively studied. From the experimental study it is concluded that the Cd value for each weir is nearly same. Also material and slight variation in thickness has no effect on the Cd value in case of rectangular sharp crested weir.

  14. A poisonous surprise under the coat of the African crested rat.

    Science.gov (United States)

    Kingdon, Jonathan; Agwanda, Bernard; Kinnaird, Margaret; O'Brien, Timothy; Holland, Christopher; Gheysens, Thomas; Boulet-Audet, Maxime; Vollrath, Fritz

    2012-02-22

    Plant toxins are sequestered by many animals and the toxicity is frequently advertised by aposematic displays to deter potential predators. Such 'unpalatability by appropriation' is common in many invertebrate groups and also found in a few vertebrate groups. However, potentially lethal toxicity by acquisition has so far never been reported for a placental mammal. Here, we describe complex morphological structures and behaviours whereby the African crested rat, Lophiomys imhausi, acquires, dispenses and advertises deterrent toxin. Roots and bark of Acokanthera schimperi (Apocynaceae) trees are gnawed, masticated and slavered onto highly specialized hairs that wick up the compound, to be delivered whenever the animal is bitten or mouthed by a predator. The poison is a cardenolide, closely resembling ouabain, one of the active components in a traditional African arrow poison long celebrated for its power to kill elephants.

  15. Coastal defence through low crested breakwater structures: jumping out of the frying pan into the fire?

    Science.gov (United States)

    Munari, Cristina; Corbau, Corinne; Simeoni, Umberto; Mistri, Michele

    2011-08-01

    The Adriatic coast of Punta Marina (Ravenna) is protected by 3-km long low crested breakwater structures (LCSs). Through a 3-years long multidisciplinar study, we assessed the impact of such defensive structures on environmental and biological condition. LCSs create pools where conditions are very different from the surrounding nearshore system. Mechanical disturbance by currents and waves varied greatly in intensity and frequency between seaward and landward sides of the structures. Sedimentary budget was positive at the landward side, but it was due to a gain on the seafloor and not on the emerged beach. The budget at seaward was negative. LCSs determine differences in benthic assemblages, alter the seasonal pattern of communities, and modify seasonal fluctuations of animal assemblages. Landward sheltered areas can be seen as "lagoonal island" surrounded by a "sea of marine habitat". Differences in ecological quality status, obtained through M-AMBI, are due to the sum of these factors. PMID:21722927

  16. Mediastinitis after cardiac transplantation

    Directory of Open Access Journals (Sweden)

    Noedir A. G. Stolf

    2000-05-01

    Full Text Available OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were performed, 12 (5.6% of the transplanted patients developed confirmed mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3±10.0 years and 10 (83.3% patients were males. Seven (58.3% patients showed sternal stability on palpation, 4 (33.3% patients had pleural empyema, and 2 (16.7% patients did not show purulent secretion draining through the wound. RESULTS: Staphylococcus aureus was the infectious agent identified in the wound secretion or in the mediastinum, or both, in 8 (66.7% patients. Staphylococcus epidermidis was identified in 2 (16.7% patients, Enterococcus faecalis in 1 (8.3% patient, and the cause of mediastinitis could not be determined in 1 (8.3% patient. Surgical treatment was performed on an emergency basis, and the extension of the débridement varied with local conditions. In 2 (16.7% patients, we chose to leave the surgical wound open and performed daily dressings with granulated sugar. Total sternal resection was performed in only 1 (8.3% patient. Out of this series, 5 (41.7% patients died, and the causes of death were related to the infection. Autopsy revealed persistence of mediastinitis in 1 (8.3% patient. CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical drainage have changed the natural evolution of this disease. Nevertheless, observance of the basic precepts of prophylaxis of infection is still the best way to treat mediastinitis.

  17. Platelets and cardiac arrhythmia

    Directory of Open Access Journals (Sweden)

    Jonas S De Jong

    2010-12-01

    Full Text Available Sudden cardiac death remains one of the most prevalent modes of death in industrialized countries, and myocardial ischemia due to thrombotic coronary occlusion is its primary cause. The role of platelets in the occurrence of SCD extends beyond coronary flow impairment by clot formation. Here we review the substances released by platelets during clot formation and their arrhythmic properties. Platelet products are released from three types of platelet granules: dense core granules, alpha-granules, and platelet lysosomes. The physiologic properties of dense granule products are of special interest as a potential source of arrhythmic substances. They are released readily upon activation and contain high concentrations of serotonin, histamine, purines, pyrimidines, and ions such as calcium and magnesium. Potential arrhythmic mechanisms of these substances, e.g. serotonin and high energy phosphates, include induction of coronary constriction, calcium overloading, and induction of delayed after-depolarizations. Alpha-granules produce thromboxanes and other arachidonic acid products with many potential arrhythmic effects mediated by interference with cardiac sodium, calcium and potassium channels. Alpha-granules also contain hundreds of proteins that could potentially serve as ligands to receptors on cardiomyocytes. Lysosomal products probably do not have an important arrhythmic effect. Platelet products and ischemia can induce coronary permeability, thereby enhancing interaction with surrounding cardiomyocytes. Antiplatelet therapy is known to improve survival after myocardial infarction. Although an important part of this effect results from prevention of coronary clot formation, there is evidence to suggest that antiplatelet therapy also induces anti-arrhythmic effects during ischemia by preventing the release of platelet activation products.

  18. Root Mean Square Acceleration (RMS, Crest Factor and Hand- Arm Vibration Dose Value In Tiller Users

    Directory of Open Access Journals (Sweden)

    PARVIN NASSIRI

    2015-10-01

    Full Text Available The purpose of this study was to assess exposure to hand-arm vibration in tiller users, Forty users of tiller in northeastern provinces of Iran were examined to measure hand-arm vibration parameters such as root mean square acceleration (RMS, total equivalent acceleration, Vibration Dose Value (VDV and crest factor in three directions (x, y, and z and various operating modes for comparing them with the relevant permitted standard levels. The hand-arm vibration measurement was done according to the standards ISO 5349-1 and ISO 5349-2. The obtained results indicated that the exposure level in three modes of rota-tilling, transportation and idling were equal to 16.95, 14.16 and 8.65 m/s2, respectively. In all measurement modes, the exposure to vibration in the direction x was greater than that of y and z. Moreover, the average crest factor was calculated less than six. The highest vibration dose values were measured in rota-tilling mode when the tiller was in 2nd  gear (60.76 m/s1.75 and 1st gear (56.83 m/s1.75. The results indicated that the permitted working time was only few seconds and there was a risk of musculoskeletal disorders. The present study emphasizes on the need for interventional and control managerial measures to eliminate or reduce hand-arm vibration transmitted to the tiller users' hands for avoiding major problems such as musculoskeletal disorders, discomfort and  premature fatigue. In this regard, further studies are required to identify vibration sources in different types of tillers.

  19. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  20. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.