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Sample records for heart neural crest

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

    International Nuclear Information System (INIS)

    Kirby, M.; Stewart, D.

    1984-01-01

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

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

    Science.gov (United States)

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

    2003-08-01

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

  3. 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.

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  5. Neural crest contributions to the lamprey head

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    McCauley, David W.; Bronner-Fraser, Marianne

    2003-01-01

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

  6. Recycling signals in the neural crest

    OpenAIRE

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

    2006-01-01

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

  7. Recycling signals in the neural crest.

    Science.gov (United States)

    Taneyhill, Lisa A; Bronner-Fraser, Marianne

    2005-01-01

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

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

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    Noisa, Parinya; Raivio, Taneli

    2014-09-01

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

  9. 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.

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

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    Sittewelle, Méghane; Monsoro-Burq, Anne H

    2018-05-31

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

  11. The neural crest migrating into the 21st century

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    Bronner, Marianne E.; Simões-Costa, Marcos

    2016-01-01

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

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

    OpenAIRE

    Gandhi, Shashank; Bronner, Marianne E.

    2018-01-01

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

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

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    Jiejing Li

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

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

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

    2018-03-01

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

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

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    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.

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

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    Pla, Patrick; Monsoro-Burq, Anne H

    2018-05-28

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

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

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

    2017-12-01

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

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

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

    2003-05-27

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

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

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

    2008-05-01

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

  20. 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 ...

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

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    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.

  2. Establishing neural crest identity: a gene regulatory recipe

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    Simões-Costa, Marcos; Bronner, Marianne E.

    2015-01-01

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

  3. Modelling collective cell migration of neural crest.

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    Szabó, András; Mayor, Roberto

    2016-10-01

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

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

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    Hall, Brian K

    2018-04-10

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

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

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    Meulemans, Daniel; Bronner-Fraser, Marianne

    2002-01-01

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

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

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    M La Noce

    2014-10-01

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

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

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

    2015-05-01

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

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

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

    2003-12-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2018-01-15

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

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

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.20.AllAg.hESC_derived_neural_crests hg19 RNA polymerase Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.05.AllAg.hESC_derived_neural_crests hg19 RNA polymerase Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Pol.PSC.10.AllAg.hESC_derived_neural_crests hg19 RNA polymerase Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.PSC.10.AllAg.hESC_derived_neural_crests.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Unc.PSC.20.AllAg.hESC_derived_neural_crests hg19 Unclassified Pluripotent stem cell hESC derived neural... crests SRX059366 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

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

    Lifescience Database Archive (English)

    Full Text Available Unc.PSC.05.AllAg.hESC_derived_neural_crests hg19 Unclassified Pluripotent stem cell hESC derived neural... crests SRX059366 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.PSC.05.AllAg.hESC_derived_neural_crests.bed ...

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  18. 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.

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

    Science.gov (United States)

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

    2011-01-15

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

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

    Full Text Available NoD.PSC.20.AllAg.hESC_derived_neural_crests hg19 No description Pluripotent stem cell hESC derived neural... crests http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.PSC.20.AllAg.hESC_derived_neural_crests.bed ...

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

    Science.gov (United States)

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

    1999-02-01

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

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Directory of Open Access Journals (Sweden)

    Tomoko Horikiri

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

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

    Science.gov (United States)

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

    2018-03-06

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

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

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

    Science.gov (United States)

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

    2001-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Youngshik Choe

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

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Science.gov (United States)

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

    2004-10-01

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

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

    Science.gov (United States)

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

    2002-01-01

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

  2. 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...

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

    Science.gov (United States)

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

    2017-12-01

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

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

    2018-01-03

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

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

    Science.gov (United States)

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

    1995-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sophie R. Miller

    2017-03-01

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

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

    Science.gov (United States)

    Barriga, Elias H.; Maxwell, Patrick H.

    2013-01-01

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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Slack Jonathan MW

    2007-05-01

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

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

  12. 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.

  13. 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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Kalcheim Chaya

    2008-10-01

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

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

    Science.gov (United States)

    Green, Stephen A; Bronner, Marianne E

    2014-01-01

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

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

    Science.gov (United States)

    Alfandari, Dominique; Taneyhill, Lisa A

    2018-02-24

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

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

    DEFF Research Database (Denmark)

    Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

    2009-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

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

  20. CREST Revealed

    DEFF Research Database (Denmark)

    Rapp, Hermann; Parisi, Cristiana; Bridgeman, Alfia

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-06-15

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2016-01-01

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

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

    Science.gov (United States)

    Tovar, Juan A

    2007-06-01

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

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

    Science.gov (United States)

    Barriga, Elias H; Mayor, Roberto

    2015-01-01

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

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

    Science.gov (United States)

    Dupin, Elisabeth; Le Douarin, Nicole M

    2014-09-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

    Mundell, Nathan A; Labosky, Patricia A

    2011-02-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2014-09-26

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

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

    Science.gov (United States)

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

    2008-10-17

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

  15. 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.

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

    Science.gov (United States)

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

    2009-01-01

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

  17. Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart.

    Science.gov (United States)

    Poelmann, Robert E; Gittenberger-de Groot, Adriana C; Biermans, Marcel W M; Dolfing, Anne I; Jagessar, Armand; van Hattum, Sam; Hoogenboom, Amanda; Wisse, Lambertus J; Vicente-Steijn, Rebecca; de Bakker, Merijn A G; Vonk, Freek J; Hirasawa, Tatsuya; Kuratani, Shigeru; Richardson, Michael K

    2017-01-01

    Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. We studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population) forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard) or it is vestigial (turtle). Crocodiles are unique in bearing a central shunt, the

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-08

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chaya Kalcheim

    2015-12-01

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

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

    Science.gov (United States)

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

    2006-06-15

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

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

    Science.gov (United States)

    Chandler, Ronald L; Magnuson, Terry

    2016-03-01

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

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

    International Nuclear Information System (INIS)

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

    1983-01-01

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

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

    Science.gov (United States)

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

    2007-04-01

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

  5. Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart

    Directory of Open Access Journals (Sweden)

    Robert E. Poelmann

    2017-05-01

    Full Text Available Abstract Background Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation. Results We studied embryonic stages of reptile hearts (lizard, turtle and crocodile and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells. The neural crest-derived aorto-pulmonary septum separates the pulmonary trunk from both aortae in reptiles, presenting with a left visceral and a right systemic aorta arising from the unseptated ventricle. Second heart field-derived cells function as flow dividers between both aortae and between the two pulmonary arteries. In birds, the left visceral aorta disappears early in development, while the right systemic aorta persists. This leads to a fusion of the aorto-pulmonary septum and the aortic flow divider (second heart field population forming an avian aorto-pulmonary septal complex. In mammals, there is also a second heart field-derived aortic flow divider, albeit at a more distal site, while the aorto-pulmonary septum separates the aortic trunk from the pulmonary trunk. As in birds there is fusion with second heart field-derived cells albeit from the pulmonary flow divider as the right 6th pharyngeal arch artery disappears, resulting in a mammalian aorto-pulmonary septal complex. In crocodiles, birds and mammals, the main septal and parietal endocardial cushions receive neural crest cells that are functional in fusion and myocardialization of the outflow tract septum. Longer-lasting septation in crocodiles demonstrates a heterochrony in development. In other reptiles with no indication of incursion of neural crest cells, there is either no myocardialized outflow tract septum (lizard or it is vestigial (turtle. Crocodiles

  6. 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...

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

    Directory of Open Access Journals (Sweden)

    Matthias Schürmann

    2014-07-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2009-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  13. The association of congenital neuroblastoma and congenital heart disease

    International Nuclear Information System (INIS)

    Bellah, R.; D'Andrea, A.; Children's Hospital, Boston, MA; Darillis, E.; Fellows, K.E.

    1989-01-01

    Several authors have reported an association between neuroblastoma and congenital heart disease; others contend that, unlike specific wellknown associations between malignancy and congenital defects (Wilm's tumor and aniridia, leukemia and Down's syndrome), no real relationship exists. We present three cases of cyanotic congenital heart disease in which subclinical neuroblastoma was found. We speculate that abnormal neural crest cell migration and development may be a common link between cardiac malformations and congenital neuroblastoma. (orig.)

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

    Science.gov (United States)

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

    2012-06-02

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

  18. 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.

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

    Czech Academy of Sciences Publication Activity Database

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2006-09-01

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

  4. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2008-01-16

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

  7. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jo Richardson

    2016-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Allyson E Kennedy

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

  11. Application of Artificial Neural Networks in the Heart Electrical Axis Position Conclusion Modeling

    Science.gov (United States)

    Bakanovskaya, L. N.

    2016-08-01

    The article touches upon building of a heart electrical axis position conclusion model using an artificial neural network. The input signals of the neural network are the values of deflections Q, R and S; and the output signal is the value of the heart electrical axis position. Training of the network is carried out by the error propagation method. The test results allow concluding that the created neural network makes a conclusion with a high degree of accuracy.

  12. 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.

  13. 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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2008-05-15

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

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

    Science.gov (United States)

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

    2015-01-15

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

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

  18. 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

  19. 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.

  20. Dynamic neural networking as a basis for plasticity in the control of heart rate.

    Science.gov (United States)

    Kember, G; Armour, J A; Zamir, M

    2013-01-21

    A model is proposed in which the relationship between individual neurons within a neural network is dynamically changing to the effect of providing a measure of "plasticity" in the control of heart rate. The neural network on which the model is based consists of three populations of neurons residing in the central nervous system, the intrathoracic extracardiac nervous system, and the intrinsic cardiac nervous system. This hierarchy of neural centers is used to challenge the classical view that the control of heart rate, a key clinical index, resides entirely in central neuronal command (spinal cord, medulla oblongata, and higher centers). Our results indicate that dynamic networking allows for the possibility of an interplay among the three populations of neurons to the effect of altering the order of control of heart rate among them. This interplay among the three levels of control allows for different neural pathways for the control of heart rate to emerge under different blood flow demands or disease conditions and, as such, it has significant clinical implications because current understanding and treatment of heart rate anomalies are based largely on a single level of control and on neurons acting in unison as a single entity rather than individually within a (plastically) interconnected network. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Hopfield neural network and optical fiber sensor as intelligent heart rate monitor

    Science.gov (United States)

    Mutter, Kussay Nugamesh

    2018-01-01

    This paper presents a design and fabrication of an intelligent fiber-optic sensor used for examining and monitoring heart rate activity. It is found in the literature that the use of fiber sensors as heart rate sensor is widely studied. However, the use of smart sensors based on Hopfield neural networks is very low. In this work, the sensor is a three fibers without cladding of about 1 cm, fed by laser light of 1550 nm of wavelength. The sensing portions are mounted with a micro sensitive diaphragm to transfer the pulse pressure on the left radial wrist. The influenced light intensity will be detected by a three photodetectors as inputs into the Hopfield neural network algorithm. The latter is a singlelayer auto-associative memory structure with a same input and output layers. The prior training weights are stored in the net memory for the standard recorded normal heart rate signals. The sensors' heads work on the reflection intensity basis. The novelty here is that the sensor uses a pulse pressure and Hopfield neural network in an integrity approach. The results showed a significant output measurements of heart rate and counting with a plausible error rate.

  2. Segmentation of Drosophila Heart in Optical Coherence Microscopy Images Using Convolutional Neural Networks

    OpenAIRE

    Duan, Lian; Qin, Xi; He, Yuanhao; Sang, Xialin; Pan, Jinda; Xu, Tao; Men, Jing; Tanzi, Rudolph E.; Li, Airong; Ma, Yutao; Zhou, Chao

    2018-01-01

    Convolutional neural networks are powerful tools for image segmentation and classification. Here, we use this method to identify and mark the heart region of Drosophila at different developmental stages in the cross-sectional images acquired by a custom optical coherence microscopy (OCM) system. With our well-trained convolutional neural network model, the heart regions through multiple heartbeat cycles can be marked with an intersection over union (IOU) of ~86%. Various morphological and dyn...

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Cornelia von Levetzow

    2011-04-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

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

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    I-Chen Li

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

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

    Science.gov (United States)

    McLennan, Rebecca; Kulesa, Paul M.

    2011-01-01

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

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

    Science.gov (United States)

    Nie, Xuguang; Wang, Qin; Jiao, Kai

    2014-01-01

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

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

    Science.gov (United States)

    Perris, R; Perissinotto, D

    2000-07-01

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

  11. 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.

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

    Science.gov (United States)

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

    2012-08-15

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

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

    Directory of Open Access Journals (Sweden)

    Michèle Rouleau

    2011-01-01

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

  15. 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....

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

    Science.gov (United States)

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

    2016-06-15

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

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

    Science.gov (United States)

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

    2018-05-25

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

  18. Frequency of Congenital Heart Diseases in Prelingual Sensory-Neural Deaf Children

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    Masoud Motasaddi Zarandy

    2016-03-01

    Full Text Available Introduction: Hearing impairment is the most frequent sensorial congenital defect in newborns and has increased to 2–4 cases per 1,000 live births. Sensory-neural hearing loss (SNHL accounts for more than 90% of all hearing loss. This disorder is associated with other congenital disorders such as renal, skeletal, ocular, and cardiac disorders. Given that congenital heart diseases are life-threatening, we decided to study the frequency of congenital heart diseases in children with congenital sensory-neural deafness.  Materials and Methods: All children who had undergone cochlear implantation surgery due to SNHL and who had attended our hospital for speech therapy during 2008–2011 were evaluated by Doppler echocardiography.  Results: Thirty-one children (15 boys and 16 girls with a mean age of 55.70 months were examined, and underwent electrocardiography (ECG and echocardiography. None of the children had any signs of heart problems in their medical records. Most of their heart examinations were normal, one patient had expiratory wheeze, four (12% had mid-systolic click, and four (12% had an intensified S1 sound. In echocardiography, 15 children (46% had mitral valve prolapse (MVP and two (6% had minimal mitral regurgitation (MR. Mean ejection fraction (EF was 69% and the mean fractional shortening (FS was 38%.  Conclusion:  This study indicates the need for echocardiography and heart examinations in children with SNHL.

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

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2017-03-01

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

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

    Science.gov (United States)

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

    2014-09-25

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

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Heidi Bildsoe

    2016-12-01

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

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

    International Nuclear Information System (INIS)

    Basu, S.; Joseph, J.K.

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chengqun Ju

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

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

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    Timothy R. Gershon

    2005-06-01

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

  6. 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

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

    Science.gov (United States)

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

    2017-11-01

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

  8. Convolutional neural networks for the detection of diseased hearts using CT images and left atrium patches

    Science.gov (United States)

    Dormer, James D.; Halicek, Martin; Ma, Ling; Reilly, Carolyn M.; Schreibmann, Eduard; Fei, Baowei

    2018-02-01

    Cardiovascular disease is a leading cause of death in the United States. The identification of cardiac diseases on conventional three-dimensional (3D) CT can have many clinical applications. An automated method that can distinguish between healthy and diseased hearts could improve diagnostic speed and accuracy when the only modality available is conventional 3D CT. In this work, we proposed and implemented convolutional neural networks (CNNs) to identify diseased hears on CT images. Six patients with healthy hearts and six with previous cardiovascular disease events received chest CT. After the left atrium for each heart was segmented, 2D and 3D patches were created. A subset of the patches were then used to train separate convolutional neural networks using leave-one-out cross-validation of patient pairs. The results of the two neural networks were compared, with 3D patches producing the higher testing accuracy. The full list of 3D patches from the left atrium was then classified using the optimal 3D CNN model, and the receiver operating curves (ROCs) were produced. The final average area under the curve (AUC) from the ROC curves was 0.840 +/- 0.065 and the average accuracy was 78.9% +/- 5.9%. This demonstrates that the CNN-based method is capable of distinguishing healthy hearts from those with previous cardiovascular disease.

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

    Science.gov (United States)

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

    2016-04-01

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

  10. Design of a heart rate controller for treadmill exercise using a recurrent fuzzy neural network.

    Science.gov (United States)

    Lu, Chun-Hao; Wang, Wei-Cheng; Tai, Cheng-Chi; Chen, Tien-Chi

    2016-05-01

    In this study, we developed a computer controlled treadmill system using a recurrent fuzzy neural network heart rate controller (RFNNHRC). Treadmill speeds and inclines were controlled by corresponding control servo motors. The RFNNHRC was used to generate the control signals to automatically control treadmill speed and incline to minimize the user heart rate deviations from a preset profile. The RFNNHRC combines a fuzzy reasoning capability to accommodate uncertain information and an artificial recurrent neural network learning process that corrects for treadmill system nonlinearities and uncertainties. Treadmill speeds and inclines are controlled by the RFNNHRC to achieve minimal heart rate deviation from a pre-set profile using adjustable parameters and an on-line learning algorithm that provides robust performance against parameter variations. The on-line learning algorithm of RFNNHRC was developed and implemented using a dsPIC 30F4011 DSP. Application of the proposed control scheme to heart rate responses of runners resulted in smaller fluctuations than those produced by using proportional integra control, and treadmill speeds and inclines were smoother. The present experiments demonstrate improved heart rate tracking performance with the proposed control scheme. The RFNNHRC scheme with adjustable parameters and an on-line learning algorithm was applied to a computer controlled treadmill system with heart rate control during treadmill exercise. Novel RFNNHRC structure and controller stability analyses were introduced. The RFNNHRC were tuned using a Lyapunov function to ensure system stability. The superior heart rate control with the proposed RFNNHRC scheme was demonstrated with various pre-set heart rates. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. HEART ABNORMALITY CLASSIFICATIONS USING FOURIER TRANSFORMS METHOD AND NEURAL NETWORKS

    Directory of Open Access Journals (Sweden)

    Endah Purwanti

    2014-05-01

    Full Text Available Health problems with cardiovascular system disorder are still ranked high globally. One way to detect abnormalities in the cardiovascular system especially in the heart is through the electrocardiogram (ECG reading. However, reading ECG recording needs experience and expertise, software-based neural networks has designed to help identify any abnormalities ofthe heart through electrocardiogram digital image. This image is processed using image processing methods to obtain ordinate chart which representing the heart’s electrical potential. Feature extraction using Fourier transforms which are divided into several numbers of coefficients. As the software input, Fourier transforms coefficient have been normalized. Output of this software is divided into three classes, namely heart with atrial fibrillation, coronary heart disease and normal. Maximum accuracy rate ofthis software is 95.45%, with the distribution of the Fourier transform coefficients 1/8 and number of nodes 5, while minimum accuracy rate of this software at least 68.18% by distribution of the Fourier transform coefficients 1/32 and the number of nodes 32. Overall result accuracy rate of this software has an average of86.05% and standard deviation of7.82.

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

    Science.gov (United States)

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

    2016-06-01

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

  13. Neural control hierarchy of the heart has not evolved to deal with myocardial ischemia.

    Science.gov (United States)

    Kember, G; Armour, J A; Zamir, M

    2013-08-01

    The consequences of myocardial ischemia are examined from the standpoint of the neural control system of the heart, a hierarchy of three neuronal centers residing in central command, intrathoracic ganglia, and intrinsic cardiac ganglia. The basis of the investigation is the premise that while this hierarchical control system has evolved to deal with "normal" physiological circumstances, its response in the event of myocardial ischemia is unpredictable because the singular circumstances of this event are as yet not part of its evolutionary repertoire. The results indicate that the harmonious relationship between the three levels of control breaks down, because of a conflict between the priorities that they have evolved to deal with. Essentially, while the main priority in central command is blood demand, the priority at the intrathoracic and cardiac levels is heart rate. As a result of this breakdown, heart rate becomes less predictable and therefore less reliable as a diagnostic guide as to the traumatic state of the heart, which it is commonly used as such following an ischemic event. On the basis of these results it is proposed that under the singular conditions of myocardial ischemia a determination of neural control indexes in addition to cardiovascular indexes has the potential of enhancing clinical outcome.

  14. Neural Network for Determining Risk Rate of Post-Heart Stroke Patients

    Directory of Open Access Journals (Sweden)

    Oldřich Trenz

    2014-01-01

    Full Text Available The ischemic heart disease presents an important health problem that affects a great part of the population and is the cause of one third of all deaths in the Czech Republic. The availability of data describing the patients’ prognosis enables their further analysis, with the aim of lowering the patients’ risk, by proposing optimum treatment. The main reason for creating the neural network model is not only to automate the process of establishing the risk rate of patients suffering from ischemic heart disease, but also to adapt it for practical use in clinical conditions. Our aim is to identify especially the specific group of risk-rate patients whose well-timed preventive care can improve the quality and prolong the length of their lives.The aim of the paper is to propose a patient-parameter structure, using which we could create a suitable model based on a self-taught neural network. The emphasis is placed on identifying key descriptive parameters (in the form of a reduction of the available descriptive parameters that are crucial for identifying the required patients, and simultaneously to achieve a portability of the model among individual clinical workplaces (availability of parameters.

  15. 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.

  16. Sagittal crest formation in great apes and gibbons.

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

  18. Whistler wave trapping in a density crest

    International Nuclear Information System (INIS)

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

    1979-11-01

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

  19. Sagittal crest formation in great apes and gibbons

    OpenAIRE

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

  1. Variations of CITED2 are associated with congenital heart disease (CHD in Chinese population.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    Full Text Available CITED2 was identified as a cardiac transcription factor which is essential to the heart development. Cited2-deficient mice showed cardiac malformations, adrenal agenesis and neural crest defects. To explore the potential impact of mutations in CITED2 on congenital heart disease (CHD in humans, we screened the coding region of CITED2 in a total of 700 Chinese people with congenital heart disease and 250 healthy individuals as controls. We found five potential disease-causing mutations, p.P140S, p.S183L, p.S196G, p.Ser161delAGC and p. Ser192_Gly193delAGCGGC. Two mammalian two-hybrid assays showed that the last four mutations significantly affected the interaction between p300CH1 and CITED2 or HIF1A. Further studies showed that four CITED2 mutations recovered the promoter activity of VEGF by decreasing its competitiveness with HIF1A for binding to p300CH1 and three mutations decreased the consociation of TFAP2C and CITED2 in the transactivation of PITX2C. Both VEGF and PITX2C play very important roles in cardiac development. In conclusion, we demonstrated that CITED2 has a potential causative impact on congenital heart disease.

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

    Directory of Open Access Journals (Sweden)

    Lu Li

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

  3. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    Science.gov (United States)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

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

    OpenAIRE

    Emad4 AbdulGabbar

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anders Lanzén

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

  6. Degradation processes and the methods of securing wall crests

    Directory of Open Access Journals (Sweden)

    Maciej Trochonowicz

    2017-12-01

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

  7. Crest syndrome

    International Nuclear Information System (INIS)

    Koch, B.; Roedl, W.

    1988-01-01

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

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

    Science.gov (United States)

    Bronner, Marianne E

    2012-11-01

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

  9. Lessons learned from the EU project T-CREST

    DEFF Research Database (Denmark)

    Schoeberl, Martin

    2016-01-01

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

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

    Science.gov (United States)

    Mitani, S; Okamoto, H

    1991-05-01

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

  11. The neural crest and neural crest cells

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

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

  12. Neural Crossroads in the Hematopoietic Stem Cell Niche.

    Science.gov (United States)

    Agarwala, Sobhika; Tamplin, Owen J

    2018-05-29

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Kawakami Minoru

    2011-11-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2005-07-01

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

  18. Heart murmur detection based on wavelet transformation and a synergy between artificial neural network and modified neighbor annealing methods.

    Science.gov (United States)

    Eslamizadeh, Gholamhossein; Barati, Ramin

    2017-05-01

    Early recognition of heart disease plays a vital role in saving lives. Heart murmurs are one of the common heart problems. In this study, Artificial Neural Network (ANN) is trained with Modified Neighbor Annealing (MNA) to classify heart cycles into normal and murmur classes. Heart cycles are separated from heart sounds using wavelet transformer. The network inputs are features extracted from individual heart cycles, and two classification outputs. Classification accuracy of the proposed model is compared with five multilayer perceptron trained with Levenberg-Marquardt, Extreme-learning-machine, back-propagation, simulated-annealing, and neighbor-annealing algorithms. It is also compared with a Self-Organizing Map (SOM) ANN. The proposed model is trained and tested using real heart sounds available in the Pascal database to show the applicability of the proposed scheme. Also, a device to record real heart sounds has been developed and used for comparison purposes too. Based on the results of this study, MNA can be used to produce considerable results as a heart cycle classifier. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-01

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

  1. Using recurrent neural network models for early detection of heart failure onset.

    Science.gov (United States)

    Choi, Edward; Schuetz, Andy; Stewart, Walter F; Sun, Jimeng

    2017-03-01

    We explored whether use of deep learning to model temporal relations among events in electronic health records (EHRs) would improve model performance in predicting initial diagnosis of heart failure (HF) compared to conventional methods that ignore temporality. Data were from a health system's EHR on 3884 incident HF cases and 28 903 controls, identified as primary care patients, between May 16, 2000, and May 23, 2013. Recurrent neural network (RNN) models using gated recurrent units (GRUs) were adapted to detect relations among time-stamped events (eg, disease diagnosis, medication orders, procedure orders, etc.) with a 12- to 18-month observation window of cases and controls. Model performance metrics were compared to regularized logistic regression, neural network, support vector machine, and K-nearest neighbor classifier approaches. Using a 12-month observation window, the area under the curve (AUC) for the RNN model was 0.777, compared to AUCs for logistic regression (0.747), multilayer perceptron (MLP) with 1 hidden layer (0.765), support vector machine (SVM) (0.743), and K-nearest neighbor (KNN) (0.730). When using an 18-month observation window, the AUC for the RNN model increased to 0.883 and was significantly higher than the 0.834 AUC for the best of the baseline methods (MLP). Deep learning models adapted to leverage temporal relations appear to improve performance of models for detection of incident heart failure with a short observation window of 12-18 months. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  3. Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs.

    Science.gov (United States)

    Ho, Lin; Hsu, Shan-Hui

    2018-04-01

    3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ. The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress ∼190 Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14 days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be

  4. 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.

  5. Cryoglobulinemic vasculitis in a patient with CREST syndrome.

    Science.gov (United States)

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

    2014-10-01

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

  6. Design Guidelines for Low Crested Structures

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Lamberti, Alberto

    2004-01-01

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

  7. Dysregulated endocardial TGFβ signaling and mesenchymal transformation result in heart outflow tract septation failure.

    Science.gov (United States)

    Ma, Mancheong; Li, Peng; Shen, Hua; Estrada, Kristine D; Xu, Jian; Kumar, S Ram; Sucov, Henry M

    2016-01-01

    Heart outflow tract septation in mouse embryos carrying mutations in retinoic acid receptor genes fails with complete penetrance. In this mutant background, ectopic TGFβ signaling in the distal outflow tract is responsible for septation failure, but it was uncertain what tissue was responsive to ectopic TGFβ and why this response interfered with septation. By combining RAR gene mutation with tissue-specific Cre drivers and a conditional type II TGFβ receptor (Tgfbr2) allele, we determined that ectopic activation of TGFβ signaling in the endocardium is responsible for septation defects. Ectopic TGFβ signaling results in ectopic mesenchymal transformation of the endocardium and thereby in improperly constituted distal OFT cushions. Our analysis highlights the interactions between myocardium, endocardium, and neural crest cells in outflow tract morphogenesis, and demonstrates the requirement for proper TGFβ signaling in outflow tract cushion organization and septation. Copyright © 2015. Published by Elsevier Inc.

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  9. 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.…

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

    Directory of Open Access Journals (Sweden)

    Emad4 AbdulGabbar

    2013-05-01

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

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Karl-F. Bergeron

    2016-11-01

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

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

    NARCIS (Netherlands)

    T. Baardman (Taco); M.V. Zwier (Mathijs V.); L.J. Wisse (Lambertus); A.C. Gittenberger-De Groot (Adriana); W.S. Kerstjens-Frederikse (Wilhelmina); R.M.W. Hofstra (Robert); A. Jurdzinski (Angelika); B.P. Hierck (Beerend); M.R.M. Jongbloed (Monique); R.M.F. Berger (Rolf); T. Plösch (Torsten); M.C. DeRuiter (Marco)

    2016-01-01

    textabstractLipoprotein-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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Albert Prieto-Márquez

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

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

    Science.gov (United States)

    Prieto-Márquez, Albert; Wagner, Jonathan R

    2013-01-01

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

  17. Syndromic Hirschsprung's disease and associated congenital heart disease: a systematic review.

    Science.gov (United States)

    Duess, Johannes W; Puri, Prem

    2015-08-01

    Hirschsprung's disease (HD) occurs as an isolated phenotype in 70% of infants and is associated with additional congenital anomalies or syndromes in approximately 30% of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5-8% of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. A systematic review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "congenital megacolon", "congenital heart disease" and "congenital heart defect" was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3%. In infants with syndromic disorders, the overall prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51%). Septation defects were recorded in 57% (atrial septal defects in 29%, ventricular septal defects in 32%), a patent ductus arteriosus in 39%, vascular abnormalities in 16%, valvular heart defects in 4% and Tetralogy of Fallot in 7%. The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities.

  18. Hydraulic model tests of an innovative dike crest design

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  20. msh/Msx gene family in neural development.

    Science.gov (United States)

    Ramos, Casto; Robert, Benoît

    2005-11-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

    Prieto-Márquez, Albert; Wagner, Jonathan R.

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Vanessa B. Martino

    2016-08-01

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

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

    Science.gov (United States)

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

    1999-04-01

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

  5. 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.

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2016-02-20

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

  8. Distinction between Neural and Vascular BOLD Oscillations and Intertwined Heart Rate Oscillations at 0.1 Hz in the Resting State and during Movement.

    Directory of Open Access Journals (Sweden)

    Gert Pfurtscheller

    Full Text Available In the resting state, blood oxygen level-dependent (BOLD oscillations with a frequency of about 0.1 Hz are conspicuous. Whether their origin is neural or vascular is not yet fully understood. Furthermore, it is not clear whether these BOLD oscillations interact with slow oscillations in heart rate (HR. To address these two questions, we estimated phase-locking (PL values between precentral gyrus (PCG and insula in 25 scanner-naïve individuals during rest and stimulus-paced finger movements in both hemispheres. PL was quantified in terms of time delay and duration in the frequency band 0.07 to 0.13 Hz. Results revealed both positive and negative time delays. Positive time delays characterize neural BOLD oscillations leading in the PCG, whereas negative time delays represent vascular BOLD oscillations leading in the insula. About 50% of the participants revealed positive time delays distinctive for neural BOLD oscillations, either with short or long unilateral or bilateral phase-locking episodes. An expected preponderance of neural BOLD oscillations was found in the left hemisphere during right-handed movement and unexpectedly in the right hemisphere during rest. Only neural BOLD oscillations were significantly associated with heart rate variability (HRV in the 0.1-Hz range in the first resting state. It is well known that participating in magnetic resonance imaging (MRI studies may be frightening and cause anxiety. In this respect it is important to note that the most significant hemispheric asymmetry (p<0.002 with a right-sided dominance of neural BOLD and a left-sided dominance of vascular BOLD oscillations was found in the first resting session in the scanner-naïve individuals. Whether the enhanced left-sided perfusion (dominance of vascular BOLD or the right-sided dominance of neural BOLD is related to the increased level of anxiety, attention or stress needs further research.

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

    Directory of Open Access Journals (Sweden)

    Yue Li

    2017-05-01

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

  10. 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.

  11. Dual embryonic origin and patterning of the pharyngeal skeleton in the axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Sefton, Elizabeth M; Piekarski, Nadine; Hanken, James

    2015-01-01

    The impressive morphological diversification of vertebrates was achieved in part by innovation and modification of the pharyngeal skeleton. Extensive fate mapping in amniote models has revealed a primarily cranial neural crest derivation of the pharyngeal skeleton. Although comparable fate maps of amphibians produced over several decades have failed to document a neural crest derivation of ventromedial elements in these vertebrates, a recent report provides evidence of a mesodermal origin of one of these elements, basibranchial 2, in the axolotl. We used a transgenic labeling protocol and grafts of labeled cells between GFP+ and white embryos to derive a fate map that describes contributions of both cranial neural crest and mesoderm to the axolotl pharyngeal skeleton, and we conducted additional experiments that probe the mechanisms that underlie mesodermal patterning. Our fate map confirms a dual embryonic origin of the pharyngeal skeleton in urodeles, including derivation of basibranchial 2 from mesoderm closely associated with the second heart field. Additionally, heterotopic transplantation experiments reveal lineage restriction of mesodermal cells that contribute to pharyngeal cartilage. The mesoderm-derived component of the pharyngeal skeleton appears to be particularly sensitive to retinoic acid (RA): administration of exogenous RA leads to loss of the second basibranchial, but not the first. Neural crest was undoubtedly critical in the evolution of the vertebrate pharyngeal skeleton, but mesoderm may have played a central role in forming ventromedial elements, in particular. When and how many times during vertebrate phylogeny a mesodermal contribution to the pharyngeal skeleton evolved remain to be resolved. © 2015 Wiley Periodicals, Inc.

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

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    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.

  13. 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.

  14. Degradation processes and the methods of securing wall crests

    OpenAIRE

    Maciej Trochonowicz; Bogusław Szmygin

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Ketan Mathavan

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

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

    Directory of Open Access Journals (Sweden)

    Pingchuan Li

    2017-12-01

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

  18. Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression.

    Science.gov (United States)

    Singh, Nikhil; Gupta, Mudit; Trivedi, Chinmay M; Singh, Manvendra K; Li, Li; Epstein, Jonathan A

    2013-05-15

    Craniofacial development is characterized by reciprocal interactions between neural crest cells and neighboring cell populations of ectodermal, endodermal and mesodermal origin. Various genetic pathways play critical roles in coordinating the development of cranial structures by modulating the growth, survival and differentiation of neural crest cells. However, the regulation of these pathways, particularly at the epigenomic level, remains poorly understood. Using murine genetics, we show that neural crest cells exhibit a requirement for the class I histone deacetylase Hdac3 during craniofacial development. Mice in which Hdac3 has been conditionally deleted in neural crest demonstrate fully penetrant craniofacial abnormalities, including microcephaly, cleft secondary palate and dental hypoplasia. Consistent with these abnormalities, we observe dysregulation of cell cycle genes and increased apoptosis in neural crest structures in mutant embryos. Known regulators of cell cycle progression and apoptosis in neural crest, including Msx1, Msx2 and Bmp4, are upregulated in Hdac3-deficient cranial mesenchyme. These results suggest that Hdac3 serves as a critical regulator of craniofacial morphogenesis, in part by repressing core apoptotic pathways in cranial neural crest cells. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Andrew A. Farke

    2013-10-01

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

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

    DEFF Research Database (Denmark)

    Fuhrman, David R.; Madsen, Per A.

    2006-01-01

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

  1. Cognitive influences on self-care decision making in persons with heart failure.

    Science.gov (United States)

    Dickson, Victoria V; Tkacs, Nancy; Riegel, Barbara

    2007-09-01

    Despite advances in management, heart failure is associated with high rates of hospitalization, poor quality of life, and early death. Education intended to improve patients' abilities to care for themselves is an integral component of disease management programs. True self-care requires that patients make decisions about symptoms, but the cognitive deficits documented in 30% to 50% of the heart failure population may make daily decision making challenging. After describing heart failure self-care as a naturalistic decision making process, we explore cognitive deficits known to exist in persons with heart failure. Problems in heart failure self-care are analyzed in relation to neural alterations associated with heart failure. As a neural process, decision making has been traced to regions of the prefrontal cortex, the same areas that are affected by ischemia, infarction, and hypoxemia in heart failure. Resulting deficits in memory, attention, and executive function may impair the perception and interpretation of early symptoms and reasoning and, thereby, delay early treatment implementation. There is compelling evidence that the neural processes critical to decision making are located in the same structures that are affected by heart failure. Because self-care requires the cognitive ability to learn, perceive, interpret, and respond, research is needed to discern how neural deficits affects these abilities, decision-making, and self-care behaviors.

  2. MR imaging findings of medial tibial crest friction

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  3. 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.

  4. TeV electron measurement with CREST experiment

    Science.gov (United States)

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

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

  5. 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...

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

    Science.gov (United States)

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

    2017-05-01

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

  7. 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.

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

    Science.gov (United States)

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

    2017-07-26

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

  9. A comparative evaluation of the in vitro penetration performance of the improved Crest complete toothbrush versus the Current Crest complete toothbrush, the Colgate Precision toothbrush and the Oral-B P40 toothbrush.

    Science.gov (United States)

    Volpenhein, D W; Handel, S E; Hughes, T J; Wild, J

    1996-01-01

    Removal of plaque and debris from interproximal surfaces during toothbrushing has generally been difficult to achieve, in large part because traditional flat-bristled toothbrushes do not offer good interproximal penetration. As a result, a number of varying bristle designs have been developed, with the rippled-design brush shown to be particularly effective at removing interproximal plaque. Recently, an existing brush, the original Crest Complete, was modified to offer a more deeply rippled version. This study evaluated the interproximal penetration of four bristle designs: rippled pattern (original Crest Complete), deeper rippled pattern (improved Crest Complete), multi-level (Colgate Precision), and flat-tufted (Oral-B P40). The study used a previously reported in vitro model for determining interproximal penetration of manual toothbrushes (J Clin Dent 5:27-33, 1994). In order to effectively mimic the in-use characteristics of toothbrushing, this model is based on analysis of videotaped consumer brushing habits, tooth morphology, and in vivo plaque tenacity characteristics and uses the three most predominantly used brushing techniques (circular, up-and-down, and back-and-forth, with the brush held at both 45 and 90 degrees to the tooth surface). In addition, the model's brush stroke length, brush force, and brush speed are likewise based on analysis of consumer brushing patterns. The results of the study indicate that the new Crest Complete with deeper rippled bristles provided significantly superior (p Colgate Precision and Oral-B brushes overall and for three of the four brush strokes tested. In addition, the new Crest Complete was found to provide significantly superior interproximal penetration to the original Crest Complete overall and in circular and up-and-down strokes, and the original Crest Complete provided superior overall interproximal penetration to the Colgate and Oral-B brushes.

  10. Structural Stability Of Detached Low Crested Breakwaters

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    OpenAIRE

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tanja Švara

    2015-03-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  16. Diversification of crested wheatgrass stands in Utah

    Science.gov (United States)

    April Hulet

    2009-01-01

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

  17. Long-throated flumes and broad-crested weirs

    NARCIS (Netherlands)

    Bos, M.G.

    1985-01-01

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

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

    Science.gov (United States)

    Sweet, Robert M

    2017-04-01

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

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

    International Nuclear Information System (INIS)

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

    2018-01-01

    To determine and compare the value of 18 F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Kasalak, Oemer; Glaudemans, Andor W.J.M.; Overbosch, Jelle; Kwee, Thomas C. [University of Groningen, Department of Radiology, Nuclear Medicine and Molecular Imaging, University Medical Center Groningen (Netherlands); Jutte, Paul C. [University of Groningen, Department of Orthopedics, University Medical Center Groningen (Netherlands)

    2018-03-15

    To determine and compare the value of {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Burenjargal Otgonsuren

    2010-12-01

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

  2. Enteric nervous system specific deletion of Foxd3 disrupts glial cell differentiation and activates compensatory enteric progenitors.

    Science.gov (United States)

    Mundell, Nathan A; Plank, Jennifer L; LeGrone, Alison W; Frist, Audrey Y; Zhu, Lei; Shin, Myung K; Southard-Smith, E Michelle; Labosky, Patricia A

    2012-03-15

    The enteric nervous system (ENS) arises from the coordinated migration, expansion and differentiation of vagal and sacral neural crest progenitor cells. During development, vagal neural crest cells enter the foregut and migrate in a rostro-to-caudal direction, colonizing the entire gastrointestinal tract and generating the majority of the ENS. Sacral neural crest contributes to a subset of enteric ganglia in the hindgut, colonizing the colon in a caudal-to-rostral wave. During this process, enteric neural crest-derived progenitors (ENPs) self-renew and begin expressing markers of neural and glial lineages as they populate the intestine. Our earlier work demonstrated that the transcription factor Foxd3 is required early in neural crest-derived progenitors for self-renewal, multipotency and establishment of multiple neural crest-derived cells and structures including the ENS. Here, we describe Foxd3 expression within the fetal and postnatal intestine: Foxd3 was strongly expressed in ENPs as they colonize the gastrointestinal tract and was progressively restricted to enteric glial cells. Using a novel Ednrb-iCre transgene to delete Foxd3 after vagal neural crest cells migrate into the midgut, we demonstrated a late temporal requirement for Foxd3 during ENS development. Lineage labeling of Ednrb-iCre expressing cells in Foxd3 mutant embryos revealed a reduction of ENPs throughout the gut and loss of Ednrb-iCre lineage cells in the distal colon. Although mutant mice were viable, defects in patterning and distribution of ENPs were associated with reduced proliferation and severe reduction of glial cells derived from the Ednrb-iCre lineage. Analyses of ENS-lineage and differentiation in mutant embryos suggested activation of a compensatory population of Foxd3-positive ENPs that did not express the Ednrb-iCre transgene. Our findings highlight the crucial roles played by Foxd3 during ENS development including progenitor proliferation, neural patterning, and glial

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

    Directory of Open Access Journals (Sweden)

    Se-Kyu Song

    2017-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-02-01

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

  5. Insights from amphioxus into the evolution of vertebrate cartilage.

    Directory of Open Access Journals (Sweden)

    Daniel Meulemans

    2007-08-01

    Full Text Available Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm.

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

    Science.gov (United States)

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

    2016-06-01

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

  7. 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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  9. Pax3 stimulates p53 ubiquitination and degradation independent of transcription.

    Directory of Open Access Journals (Sweden)

    Xiao Dan Wang

    Full Text Available Pax3 is a developmental transcription factor that is required for neural tube and neural crest development. We previously showed that inactivating the p53 tumor suppressor protein prevents neural tube and cardiac neural crest defects in Pax3-mutant mouse embryos. This demonstrates that Pax3 regulates these processes by blocking p53 function. Here we investigated the mechanism by which Pax3 blocks p53 function.We employed murine embryonic stem cell (ESC-derived neuronal precursors as a cell culture model of embryonic neuroepithelium or neural crest. Pax3 reduced p53 protein stability, but had no effect on p53 mRNA levels or the rate of p53 synthesis. Full length Pax3 as well as fragments that contained either the DNA-binding paired box or the homeodomain, expressed as GST or FLAG fusion proteins, physically associated with p53 and Mdm2 both in vitro and in vivo. In contrast, Splotch Pax3, which causes neural tube and neural crest defects in homozygous embryos, bound weakly, or not at all, to p53 or Mdm2. The paired domain and homeodomain each stimulated Mdm2-mediated ubiquitination of p53 and p53 degradation in the absence of the Pax3 transcription regulatory domains, whereas Splotch Pax3 did not stimulate p53 ubiquitination or degradation.Pax3 inactivates p53 function by stimulating its ubiquitination and degradation. This process utilizes the Pax3 paired domain and homeodomain but is independent of DNA-binding and transcription regulation. Because inactivating p53 is the only required Pax3 function during neural tube closure and cardiac neural crest development, and inactivating p53 does not require Pax3-dependent transcription regulation, this indicates that Pax3 is not required to function as a transcription factor during neural tube closure and cardiac neural crest development. These findings further suggest novel explanations for PAX3 functions in human diseases, such as in neural crest-derived cancers and Waardenburg syndrome types 1 and 3.

  10. Application of artificial neural network for medical image recognition and diagnostic decision making

    International Nuclear Information System (INIS)

    Asada, N.; Eiho, S.; Doi, K.; MacMahon, H.; Montner, S.M.; Giger, M.L.

    1989-01-01

    An artificial neural network has been applied for pattern recognition and used as a tool in an expert system. The purpose of this study is to examine the potential usefulness of the neural network approach in medical applications for image recognition and decision making. The authors designed multilayer feedforward neural networks with a back-propagation algorithm for our study. Using first-pass radionuclide ventriculograms, we attempted to identify the right and left ventricles of the heart and the lungs by training the neural network from patterns of time-activity curves. In a preliminary study, the neural network enabled identification of the lungs and heart chambers once the network was trained sufficiently by means of repeated entries of data from the same case

  11. Application of positron emission tomography in the heart

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    This report discusses experimental and clinical applications of positron emission tomography to the heart, including measurements of blood flow to the myocardium and studies of metabolism and experimental injury. Most initial clinical studies have concentrated on ischemic heart disease, but the technique also has potential for investigation of cardiomyopathies, studying the neural control of the heart, and evaluating the effects of drugs on cardiac tissues

  12. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    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.

  13. Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy

    International Nuclear Information System (INIS)

    Koyama, Keiko; Inoue, Tomio; Hasegawa, Akira; Oriuchi, Noboru; Okamoto, Eiichi; Tomaru, Yumi; Endo, Keigo

    2001-01-01

    Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p<0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p<0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r=0.80, p<0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart. (author)

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

    Directory of Open Access Journals (Sweden)

    Vaibhav P. Pai

    2012-01-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

  16. Crest Level Optimization of the Multi Level Overtopping based Wave Energy Converter Seawave Slot-Cone Generator

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Osaland, E.

    2005-01-01

    The paper describes the optimization of the crest levels and geometrical layout of the SSG structure, focusing on maximizing the obtained potential energy in the overtopping water. During wave tank testing at AAU average overtopping rates into the individual reservoirs have been measured. The ini......The paper describes the optimization of the crest levels and geometrical layout of the SSG structure, focusing on maximizing the obtained potential energy in the overtopping water. During wave tank testing at AAU average overtopping rates into the individual reservoirs have been measured....... The initial tests led to an expression describing the derivative of the overtopping rate with respect to the vertical distance. Based on this, numerical optimizations of the crest levels, for a number of combinations of wave conditions, have been performed. The hereby found optimal crest levels have been...

  17. 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.

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

    Science.gov (United States)

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

    2018-02-22

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

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

    Science.gov (United States)

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

    2014-04-01

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

  20. Myocardial function and perfusion in the CREST syndrome variant of progressive systemic sclerosis. Exercise radionuclide evaluation and comparison with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Owens, G.R.; Steen, V.D.; Rodnan, G.P.

    1984-01-01

    Myocardial function and perfusion were evaluated in 22 patients with progressive systemic sclerosis with the CREST syndrome using exercise and radionuclide techniques, pulmonary function testing, and chest roentgenography. The results were compared with a similar study of 26 patients with progressive systemic sclerosis with diffuse scleroderma. The prevalence of thallium perfusion abnormalities was similar in the groups with CREST syndrome and diffuse scleroderma, (64 percent versus 77 percent), but the defects were significantly smaller in the CREST syndrome (p less than 0.01). Reperfusion thallium defects in the absence of extramural coronary artery disease were seen in 38 percent of patients with diffuse scleroderma. This finding was not seen in any of the patients with the CREST syndrome. In diffuse scleroderma, abnormalities of both right and left ventricular function were related to larger thallium perfusion defects. In the CREST syndrome, abnormalities of left ventricular function were minor, were seen only during exercise, and were unrelated to thallium perfusion defects. Abnormal resting right ventricular function was seen in 36 percent of the patients with the CREST syndrome and was associated with an isolated decrease in diffusing capacity of carbon monoxide. It is concluded that the cardiac manifestations of the CREST syndrome are distinct from those found in diffuse scleroderma. Unlike diffuse scleroderma, abnormalities of left ventricular function in the CREST syndrome are minor and are unrelated to abnormalities of coronary perfusion. Right ventricular dysfunction in the CREST syndrome appears to be primarily related to pulmonary vascular disease

  1. 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

  2. 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.

  3. Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Piattelli, Adriano; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-12-01

    Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues received considerable interest in regenerative medicine, particularly in nerve regeneration owing to their embryonic origin and ease of harvest. Proliferation efficacy and differentiation capacity into diverse cell lineages propose dental MSCs as an in vitro tool for disease modeling. In this study, we investigated the spontaneous differentiation efficiency of dental MSCs obtained from human gingiva tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage 41, the morphology of hGMSCs changed from typical fibroblast-like shape into sphere-shaped cells with extending processes. Next-generation transcriptomics sequencing showed increased expression of neural progenitor markers such as NES, MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41. Immunocytochemistry results showed suppression of neurogenesis repressors TP53 and p21, whereas Western blot results revealed the expression of neurotrophic factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy of hGMSCs to differentiate into neural precursor cells over prolonged passages and that these cells may assist in producing novel in vitro disease models that are associated with neural development.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  5. Hydraulic Evaluation of the Crest Wing Wave Energy Converter

    DEFF Research Database (Denmark)

    Kofoed, Jens Peter; Antonishen, Michael Patrick

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

  6. Real-Time Audio Processing on the T-CREST Multicore Platform

    DEFF Research Database (Denmark)

    Ausin, Daniel Sanz; Pezzarossa, Luca; Schoeberl, Martin

    2017-01-01

    of the audio signal. This paper presents a real-time multicore audio processing system based on the T-CREST platform. T-CREST is a time-predictable multicore processor for real-time embedded systems. Multiple audio effect tasks have been implemented, which can be connected together in different configurations...... forming sequential and parallel effect chains, and using a network-onchip for intercommunication between processors. The evaluation of the system shows that real-time processing of multiple effect configurations is possible, and that the estimation and control of latency ensures real-time behavior.......Multicore platforms are nowadays widely used for audio processing applications, due to the improvement of computational power that they provide. However, some of these systems are not optimized for temporally constrained environments, which often leads to an undesired increase in the latency...

  7. Molecular Prognostic Markers in Uveal Melanoma: Expression Profiling and Genomic Studies

    NARCIS (Netherlands)

    W. Gils (Walter)

    2008-01-01

    textabstractUveal Melanomas (UMs) arise from melanocytes. This cell type originates from neural crest cells and thereby uveal melanomas share their origin with pheochromocytomas, neuroblastomas, paragangliomas and cutaneous melanomas, other tumors that develop from neural crest originating cells.

  8. Application of convolutional artificial neural networks to echocardiograms for differentiating congenital heart diseases in a pediatric population

    Science.gov (United States)

    Perrin, Douglas P.; Bueno, Alejandra; Rodriguez, Andrea; Marx, Gerald R.; del Nido, Pedro J.

    2017-03-01

    In this paper we describe a pilot study, where machine learning methods are used to differentiate between congenital heart diseases. Our approach was to apply convolutional neural networks (CNNs) to echocardiographic images from five different pediatric populations: normal, coarctation of the aorta (CoA), hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and single ventricle (SV). We used a single network topology that was trained in a pairwise fashion in order to evaluate the potential to differentiate between patient populations. In total we used 59,151 echo frames drawn from 1,666 clinical sequences. Approximately 80% of the data was used for training, and the remainder for validation. Data was split at sequence boundaries to avoid having related images in the training and validation sets. While training was done with echo images/frames, evaluation was performed for both single frame discrimination as well as sequence discrimination (by majority voting). In total 10 networks were generated and evaluated. Unlike other domains where this network topology has been used, in ultrasound there is low visual variation between classes. This work shows the potential for CNNs to be applied to this low-variation domain of medical imaging for disease discrimination.

  9. RECONSTRUCTION OF ATROPHIC MAXILLA BY ANTERIOR ILIAC CREST BONE GRAFTING VIA NEUROAXIAL BLOCKADE TECHNIQUE: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Erol CANSIZ

    2017-01-01

    Full Text Available Anterior iliac crest bone grafting is a well-established modality in the treatment of alveolar bone deficiencies. However, this procedure may also have considerable postoperative morbidity which is mostly related to general anesthesia. Postoperative pain-related complications can be managed by neuroaxial blockade techniques which provide adequate surgical analgesia and reduce postoperative pain. This clinical report describes the reconstruction of a severely atrophic maxilla with anterior iliac crest bone grafting using combined spinal epidural anesthesia. Neuroaxial blockade techniques may be a useful alternative to eliminate general anesthesia related challenges of anterior iliac crest bone grafting procedures.

  10. 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.

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2001-05-01

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

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

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

    OpenAIRE

    BORIC BRENET, KATICA ANDREA; BORIC BRENET, KATICA ANDREA

    2012-01-01

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

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

    African Journals Online (AJOL)

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

  16. Differentiation of Equine Mesenchymal Stromal Cells into Cells of Neural Lineage: Potential for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Claudia Cruz Villagrán

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSCs are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses.

  17. Neural Network-Based Coronary Heart Disease Risk Prediction Using Feature Correlation Analysis

    Directory of Open Access Journals (Sweden)

    Jae Kwon Kim

    2017-01-01

    Full Text Available Background. Of the machine learning techniques used in predicting coronary heart disease (CHD, neural network (NN is popularly used to improve performance accuracy. Objective. Even though NN-based systems provide meaningful results based on clinical experiments, medical experts are not satisfied with their predictive performances because NN is trained in a “black-box” style. Method. We sought to devise an NN-based prediction of CHD risk using feature correlation analysis (NN-FCA using two stages. First, the feature selection stage, which makes features acceding to the importance in predicting CHD risk, is ranked, and second, the feature correlation analysis stage, during which one learns about the existence of correlations between feature relations and the data of each NN predictor output, is determined. Result. Of the 4146 individuals in the Korean dataset evaluated, 3031 had low CHD risk and 1115 had CHD high risk. The area under the receiver operating characteristic (ROC curve of the proposed model (0.749 ± 0.010 was larger than the Framingham risk score (FRS (0.393 ± 0.010. Conclusions. The proposed NN-FCA, which utilizes feature correlation analysis, was found to be better than FRS in terms of CHD risk prediction. Furthermore, the proposed model resulted in a larger ROC curve and more accurate predictions of CHD risk in the Korean population than the FRS.

  18. CREST-SAFE: Snow LST validation, wetness profiler creation, and depth/SWE product development

    Science.gov (United States)

    Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Khanbilvardi, R.; Munoz Barreto, J.; Yu, Y.

    2017-12-01

    CREST-SAFE: Snow LST validation, wetness profiler creation, and depth/SWE product development The Field Snow Research Station (also referred to as Snow Analysis and Field Experiment, SAFE) is operated by the NOAA Center for Earth System Sciences and Remote Sensing Technologies (CREST) in the City University of New York (CUNY). The field station is located within the premises of the Caribou Municipal Airport (46°52'59'' N, 68°01'07'' W) and in close proximity to the National Weather Service (NWS) Regional Forecast Office. The station was established in 2010 to support studies in snow physics and snow remote sensing. The Visible Infrared Imager Radiometer Suite (VIIRS) Land Surface Temperature (LST) Environmental Data Record (EDR) and Moderate Resolution Imaging Spectroradiometer (MODIS) LST product (provided by the Terra and Aqua Earth Observing System satellites) were validated using in situ LST (T-skin) and near-surface air temperature (T-air) observations recorded at CREST-SAFE for the winters of 2013 and 2014. Results indicate that T-air correlates better than T-skin with VIIRS LST data and that the accuracy of nighttime LST retrievals is considerably better than that of daytime. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and night-time values. Results indicate that, although all the data sets showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C). Additionally, we created a liquid water content (LWC)-profiling instrument using time-domain reflectometry (TDR) at CREST-SAFE and tested it during the snow melt period (February-April) immediately after installation in 2014. Results displayed high agreement when compared to LWC estimates obtained using empirical formulas developed in previous studies, and minor improvement over wet snow LWC estimates. Lastly, to improve on global snow cover mapping, a snow product capable of estimating snow depth and snow water

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

    Directory of Open Access Journals (Sweden)

    A. Voigt

    2009-05-01

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

  20. Iliac Crest Donor Site for Children With Cleft Lip and Palate Undergoing Alveolar Bone Grafting: A Long-term Assessment.

    Science.gov (United States)

    Wheeler, Jonathan; Sanders, Megan; Loo, Stanley; Moaveni, Zac; Bartlett, Glenn; Keall, Heather; Pinkerton, Mark

    2016-05-01

    The authors aimed to accurately assess the donor site morbidity from iliac crest bone grafts for secondary bone grafting in patients with cleft lip and palate alveolar defects. Fifty patients between 3 months and 10 years following alveolar bone grafting for cleft lip and palate were entered into the study. Two-thirds of patients had no significant concerns about the donor site. The remaining third had some concerns about the appearance of their hips and less than 10% of patients expressing strong agreement with statements about concerns with shape, appearance, and self-consciousness about the iliac crest donor site. Examination findings showed the average length of scar being 5.4 cm and a third of patients having some minor palpable boney irregularities of the iliac crest. The authors found that the alveolar crest donor site is well tolerated by patients long term but has a measurable morbidity long term.

  1. Age-related changes in vertebral and iliac crest 3D bone microstructure-differences and similarities

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Jensen, Michael Vinkel; Niklassen, Andreas Steenholt

    2015-01-01

    Summary Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure...... was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes.Introduction The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between...... the bone microstructure at these skeletal sites.Methods Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19–96 years) and 39 men (23–95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified.Results For both women...

  2. Laboratory Experiments on Low-crested Breakwaters

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  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 quali...

  4. A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability.

    Science.gov (United States)

    Shaffer, Fred; McCraty, Rollin; Zerr, Christopher L

    2014-01-01

    Heart rate variability (HRV), the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF), very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges' polyvagal theory, Thayer and colleagues' neurovisceral integration model, Lehrer et al.'s resonance frequency model, and the Institute of HeartMath's coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.

  5. Comparison of the breeding biology of sympatric red-tailed Hawks, White-tailed Hawks, and Crested Caracaras in south Texas

    Science.gov (United States)

    Actkinson, M.A.; Kuvlesky, W.P.; Boal, C.W.; Brennan, L.A.; Hernandez, F.

    2009-01-01

    We compared the breeding biology of sympatric nesting Red-tailed Hawks (Buteo jamaicensis), White-tailed Hawks (Buteo albicaudatus), and Crested Caracaras (Caracara cheriway) in south Texas during 2003 and 2004. We monitored 46 breeding attempts by Red-tailed Hawks, 56 by White-tailed Hawks, and 27 by Crested Caracaras. Observed nesting success was similar for Red-tailed Hawks (62%) and Crested Caracaras (61%), but lower for White-tailed Hawks (51%). Daily survival rates (0.99) were the same for all three species. Red-tailed Hawks and White-tailed Hawks both fledged 1.13 young per nesting pair and Crested Caracaras fledged 1.39 young per nesting pair. All three species nested earlier in 2004 than in 2003; in addition, the overall nesting density of these three species almost doubled from 2003 (1.45 pairs/km2) to 2004 (2.71 pairs/km2). Estimated productivity of all three species was within the ranges reported from other studies. Given extensive and progressive habitat alteration in some areas of south Texas, and the limited distributions of White-tailed Hawks and Crested Caracaras, the presence of large ranches managed for free-range cattle production and hunting leases likely provides important habitat and may be key areas for conservation of these two species. ?? 2009 The Raptor Research Foundation, Inc.

  6. Phylogenetic patterns and correlation of key structures for jumping: bone crests and cross-sectional areas of muscles in Leptodactylus (Anura, Leptodactylidae).

    Science.gov (United States)

    Ponssa, María Laura; Fratani, Jéssica; Abdala, Virginia

    2018-05-01

    Anurans are characterized by their saltatory mode of locomotion, which is associated with a specific morphology. The coordinated action of the muscles and bones of the pelvic girdle is key to the transmission of the force of the hindlimbs to the axial skeleton during jumping. Two features are critical for optimal locomotory performance: the cross-sectional area of muscle and the bone crest attachment sites. The first character is a proxy of the force exerted by the muscle, whereas the crests are muscle attachments sites related to muscle force. The provisory relationship between these features has previously been identified and bone crest size can be used to infer the magnitude and, therefore, muscle force in fossils records. In this work, we explore the correlation between the cross-sectional area of essential muscles to the jumping mechanism (longissimus dorsi, extensor iliotibialis B, tenuissimus, puboischiofemoralis internus B, coccygeo-sacralis and coccygeo-iliacus) and the bone crests where these muscles are inserted (dorsal tubercle, dorsal crest and urostylar crest) in species of the genus Leptodactylus. This genus, along with other leptodactylids, exhibits a diversity of locomotor modes, including jumping, hopping, swimming and burrowing. We therefore analyzed the morphometric variation in the two features, cross-sectional area and bone crest area, expecting a correlation with different locomotor types. Our results showed: (i) a correlation between the urostylar crest and the cross-sectional area of the related muscles; (ii) that the bone crest surface area of urostyle and ilium and the cross-sectional area of the corresponding muscles can be utilized to infer locomotor faculties in leptodactylid frogs; and (iii) that the evolution of both characters demonstrates a general tendency from lower values in leptodactylid ancestors to higher values in the Leptodactylus genus. The results attest to the importance of the comparison of current ecological and

  7. Heart Rate Estimated from Body Movements at Six Degrees of Freedom by Convolutional Neural Networks.

    Science.gov (United States)

    Lee, Hyunwoo; Whang, Mincheol

    2018-05-01

    Cardiac activity has been monitored continuously in daily life by virtue of advanced medical instruments with microelectromechanical system (MEMS) technology. Seismocardiography (SCG) has been considered to be free from the burden of measurement for cardiac activity, but it has been limited in its application in daily life. The most important issues regarding SCG are to overcome the limitations of motion artifacts due to the sensitivity of motion sensor. Although novel adaptive filters for noise cancellation have been developed, they depend on the researcher’s subjective decision. Convolutional neural networks (CNNs) can extract significant features from data automatically without a researcher’s subjective decision, so that signal processing has been recently replaced as CNNs. Thus, this study aimed to develop a novel method to enhance heart rate estimation from thoracic movement by CNNs. Thoracic movement was measured by six-axis accelerometer and gyroscope signals using a wearable sensor that can be worn by simply clipping on clothes. The dataset was collected from 30 participants (15 males, 15 females) using 12 measurement conditions according to two physical conditions (i.e., relaxed and aroused conditions), three body postures (i.e., sitting, standing, and supine), and six movement speeds (i.e., 3.2, 4.5, 5.8, 6.4, 8.5, and 10.3 km/h). The motion data (i.e., six-axis accelerometer and gyroscope) and heart rate (i.e., electrocardiogram (ECG)) were determined as the input data and labels in the dataset, respectively. The CNN model was developed based on VGG Net and optimized by testing according to network depth and data augmentation. The ensemble network of the VGG-16 without data augmentation and the VGG-19 with data augmentation was determined as optimal architecture for generalization. As a result, the proposed method showed higher accuracy than the previous SCG method using signal processing in most measurement conditions. The three main contributions

  8. Heart Rate Estimated from Body Movements at Six Degrees of Freedom by Convolutional Neural Networks

    Directory of Open Access Journals (Sweden)

    Hyunwoo Lee

    2018-05-01

    Full Text Available Cardiac activity has been monitored continuously in daily life by virtue of advanced medical instruments with microelectromechanical system (MEMS technology. Seismocardiography (SCG has been considered to be free from the burden of measurement for cardiac activity, but it has been limited in its application in daily life. The most important issues regarding SCG are to overcome the limitations of motion artifacts due to the sensitivity of motion sensor. Although novel adaptive filters for noise cancellation have been developed, they depend on the researcher’s subjective decision. Convolutional neural networks (CNNs can extract significant features from data automatically without a researcher’s subjective decision, so that signal processing has been recently replaced as CNNs. Thus, this study aimed to develop a novel method to enhance heart rate estimation from thoracic movement by CNNs. Thoracic movement was measured by six-axis accelerometer and gyroscope signals using a wearable sensor that can be worn by simply clipping on clothes. The dataset was collected from 30 participants (15 males, 15 females using 12 measurement conditions according to two physical conditions (i.e., relaxed and aroused conditions, three body postures (i.e., sitting, standing, and supine, and six movement speeds (i.e., 3.2, 4.5, 5.8, 6.4, 8.5, and 10.3 km/h. The motion data (i.e., six-axis accelerometer and gyroscope and heart rate (i.e., electrocardiogram (ECG were determined as the input data and labels in the dataset, respectively. The CNN model was developed based on VGG Net and optimized by testing according to network depth and data augmentation. The ensemble network of the VGG-16 without data augmentation and the VGG-19 with data augmentation was determined as optimal architecture for generalization. As a result, the proposed method showed higher accuracy than the previous SCG method using signal processing in most measurement conditions. The three main

  9. 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.

  10. 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.)

  11. Spatial correlation of the ionsphere total electron content at the equatorial anomaly crest

    International Nuclear Information System (INIS)

    Huang, Y.

    1984-01-01

    The spatial correlation of the ionospheric total electron content (TEC) at the equatorial anomaly crest was studied by recording Faraday rotation angle of the ETS-II geostationary satellite at Lunping and Kaohsiung whose subionospheric points are located at 23.0 0 N, 121.0 0 N, and 20.9 0 N, 121.1 0 E, respectively, and are about 280 km apart. The results show that the spatial correlation of TEC at the equatorial crest region is smaller than that at other places. The day-to-day variabilities of TEC differences between two subionospheric points are quite large. The day-to-day variabilities of the fountain effect seem to play an important role

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

    Science.gov (United States)

    Shapiro, Michael D; Kronenberg, Zev; Li, Cai; Domyan, Eric T; Pan, Hailin; Campbell, Michael; Tan, Hao; Huff, Chad D; Hu, Haofu; Vickrey, Anna I; Nielsen, Sandra C A; Stringham, Sydney A; Hu, Hao; Willerslev, Eske; Gilbert, M Thomas P; Yandell, Mark; Zhang, Guojie; Wang, Jun

    2013-03-01

    The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.

  13. Hydraulic evaluation of the Crest Wing wave energy converter

    Energy Technology Data Exchange (ETDEWEB)

    Kofoed, J.P.; Antonishen, M.

    2008-09-15

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

  14. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos

    International Nuclear Information System (INIS)

    Zhang, Ting; Zhou, Xin-Ying; Ma, Xu-Fa; Liu, Jing-Xia

    2015-01-01

    Highlights: Using high-throughput in situ hybridization screening, we found that genes labeling the neural crest and its derivative pigment cells were sensitive to cadmium toxicity during zebrafish organogenesis, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in cadmium-exposed embryos. Based on neural crest markers, we identified the doses and times of cadmium exposure that cause damage to the zebrafish organogenesis, and we also found that compounds BIO or RA could neutralize the toxic effects of cadmium. - Abstract: Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd.

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

    Directory of Open Access Journals (Sweden)

    YanYan Mao

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

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

    Science.gov (United States)

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

    2014-01-01

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

  17. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ting, E-mail: zting@webmail.hzau.edu.cn; Zhou, Xin-Ying, E-mail: 290356082@qq.com; Ma, Xu-Fa, E-mail: xufama@mail.hzau.edu.cn; Liu, Jing-Xia, E-mail: ichliu@mail.hzau.edu.cn

    2015-10-15

    Highlights: Using high-throughput in situ hybridization screening, we found that genes labeling the neural crest and its derivative pigment cells were sensitive to cadmium toxicity during zebrafish organogenesis, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in cadmium-exposed embryos. Based on neural crest markers, we identified the doses and times of cadmium exposure that cause damage to the zebrafish organogenesis, and we also found that compounds BIO or RA could neutralize the toxic effects of cadmium. - Abstract: Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd.

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

    International Nuclear Information System (INIS)

    Maria, P.P.; Padilha Filho, J.G.; Canola, J.C.; Castro, M.B.

    2004-01-01

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

  19. SCENARIO OF AN ACCIDENT OF SOIL DAMS IN CASE OF WATER SPILL OVER A DAM CREST BY USING FAULT TREE ANALYSIS

    Directory of Open Access Journals (Sweden)

    Kuznetsov Dmitriy Viktorovich

    2016-04-01

    Full Text Available The scenario of a hydrodynamic accident of water flow over a crest of a soil dam is considered by the method of fault tree analysis, for which the basic reasons and controlled diagnostic indicators of an accident have been defined. Logical operators “AND”/”OR” were used for creation of a sequence of logically connected events, leading to an undesired event in the scenario of accident. The scenario of the accident was plotted in case of three basic reasons - an excessive settling of a dam crest, an excess flood, an inoperable spillway, taking into account the sequence of the events’ development and with observance of the necessary conditions leading to an accident. “Technical” reasons were observed in the present scenario, force majeure events were not considered. The provided scenario of the accident consists of two branches of events’ development: the left one that depends on an upstream level, and the right one that depends on settling of a dam crest. In each of the considered events an accident “the water spill over a crest of a soil dam” is possible only in case of execution of two different conditions at the same time, i.e. in case of an appropriate upstream level and the appropriate mark of a crest of a soil dam. The conditions of the accident are defined by diagnostic indices - the upstream level and settling of a dam crest, which at the same time are safety criteria of the hydraulic structure for soil dams. They allow defining the technical condition of the construction. Four possible technical conditions are suggested for the definition of technical statuses - normative, operable, limited operable, abnormal. Criteria of safety are the boundaries of the state: for loading and impact - it is the upstream level, for geometrical compliance of the construction - it is a dam crest mark.

  20. Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

    Science.gov (United States)

    Luo, Lihua; Wang, Xiaoyan; Key, Brian; Lee, Bae Hoon

    2018-01-01

    This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases. PMID:29853908

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

    Science.gov (United States)

    Mercer, Dacey; Haig, Susan; Mullins, Thomas

    2010-01-01

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

  2. Electrocardiogram (ECG Signal Modeling and Noise Reduction Using Hopfield Neural Networks

    Directory of Open Access Journals (Sweden)

    F. Bagheri

    2013-02-01

    Full Text Available The Electrocardiogram (ECG signal is one of the diagnosing approaches to detect heart disease. In this study the Hopfield Neural Network (HNN is applied and proposed for ECG signal modeling and noise reduction. The Hopfield Neural Network (HNN is a recurrent neural network that stores the information in a dynamic stable pattern. This algorithm retrieves a pattern stored in memory in response to the presentation of an incomplete or noisy version of that pattern. Computer simulation results show that this method can successfully model the ECG signal and remove high-frequency noise.

  3. Fibulin-1 Binds to Fibroblast Growth Factor 8 with High Affinity: EFFECTS ON EMBRYO SURVIVAL.

    Science.gov (United States)

    Fresco, Victor M; Kern, Christine B; Mohammadi, Moosa; Twal, Waleed O

    2016-09-02

    Fibulin-1 (FBLN1) is a member of a growing family of extracellular matrix glycoproteins that includes eight members and is involved in cellular functions such as adhesion, migration, and differentiation. FBLN1 has also been implicated in embryonic heart and valve development and in the formation of neural crest-derived structures, including aortic arch, thymus, and cranial nerves. Fibroblast growth factor 8 (FGF8) is a member of a large family of growth factors, and its functions include neural crest cell (NCC) maintenance, specifically NCC migration as well as patterning of structures formed from NCC such as outflow tract and cranial nerves. In this report, we sought to investigate whether FBLN1 and FGF8 have cooperative roles in vivo given their influence on the development of the same NCC-derived structures. Surface plasmon resonance binding data showed that FBLN1 binds tightly to FGF8 and prevents its enzymatic degradation by ADAM17. Moreover, overexpression of FBLN1 up-regulates FGF8 gene expression, and down-regulation of FBLN1 by siRNA inhibits FGF8 expression. The generation of a double mutant Fbln1 and Fgf8 mice (Fbln1(-/-) and Fgf8(-/-)) showed that haplo-insufficiency (Fbln1(+/-) and Fgf8(+/-)) resulted in increased embryonic mortality compared with single heterozygote crosses. The mortality of the FGF8/Fbln1 double heterozygote embryos occurred between 14.5 and 16.5 days post-coitus. In conclusion, FBLN1/FGF8 interaction plays a role in survival of vertebrate embryos, and reduced levels of both proteins resulted in added mortality in utero The FBLN1/FGF8 interaction may also be involved in the survival of neural crest cell population during development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Comparison of fracture site callus with iliac crest bone marrow as the source of plastic-adherent cells

    Directory of Open Access Journals (Sweden)

    Achmad Zaki

    2013-05-01

    Full Text Available Background: Red marrow has been described as the main source of mesenchymal stem cells although its aspiration and isolation from bone marrow was reported to have significant donor site morbidity. Since secondary bone healing occurs through formation of callus as the result of proliferation and differentiation of mesenchymal stem cells, callus may become alternative source for mesenchymal stem cells. In this study, we compared the number of plastic-adherent cells from fracture site callus and bone marrow of iliac crest after two and four weeks of culture.Methods: Sixteen New Zealand rabbits were fracturized at the femoral shaft. Then, these rabbits were taken care. After two weeks of fracturization, 3 mL iliac crest bone marrow aspiration and callus extraction of eight rabbits were cultured (group I. The other eight rabbits were treated equally after four weeks of fracturization (group II. Simultaneously, the cultures were observed after one and two weeks. Four weeks later, they were harvested. Cells were counted using Neubauer hemocytometer. The average number of cells between the sources and groups were statistically analyzed using the unpaired t-test. Results: In group I, there were 2.6 ± 0.1 x 104 cells in the culture of iliac crest bone marrow aspirate and 2.5 ± 0.1 x 104 cells in culture of callus extract from fracture site (p = 0.34. In group II, there were 2.7 ± 0.1 x 104 cells and 2.1 ± 0.1 x 104 cells, respectively (p < 0.001.Conclusion: Fracture site callus at the second week post-fracturization may be potential as source of plastic-adherent cells compared with iliac crest bone marrow. (Med J Indones. 2013;22:70-5Keywords: Bone marrow, fracture site callus, iliac crest, long bone, mesenchymal stem cell, plastic-adherent cells

  5. [Comparison of the Latissimus dorsi insertions on the iliac crest in chimpanzee (Pan troglodytes) and in man].

    Science.gov (United States)

    Vacher, C; Ben Hadj Yahia, S; Braun, M; Journeau, P

    2014-03-01

    Comparing to other primates, one of the most important specificities of the human anatomy are consequences of bipedalism. Although bone consequences are well known (lumbar lordosis, horizontal position of the foramen magnum, lengthening of the lower limbs, reduction of the pelvis, specialization of the foot), consequences of our locomotion on the Latissimus dorsi are still unclear. One dissection of a chimpanzee Latissimus dorsi (Pan troglodytes) has been performed and compared to 30 human Latissimus dorsi dissections (10 fresh cadavers and 20 formoled cadavers). In each dissection, the existence of direct muscular insertions on the iliac crest has been investigated and the constitution of the thoracolumbar fascia has been described. In chimpanzee dissection, a muscular direct insertion of the Latissimus dorsi was present on the iliac crest of 9 cm long. The TLF was made of the superficial and the deep fascias of the Latissimus dorsi and the superficial fascia of the erector spinae muscles which was deeper. In man, there was no direct muscular insertion of the Latissimus dorsi in 90 % of cases, the TLF was constituted the same way. This study suggests that the Latissimus dorsi has been separated from the iliac crest in man during the evolution because of the permanent bipedalism and that it stayed inserted on the iliac crest in chimpanzee because of the brachiation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. Direct Genesis of Functional Rodent and Human Schwann Cells from Skin Mesenchymal Precursors

    Directory of Open Access Journals (Sweden)

    Matthew P. Krause

    2014-07-01

    Full Text Available Recent reports of directed reprogramming have raised questions about the stability of cell lineages. Here, we have addressed this issue, focusing upon skin-derived precursors (SKPs, a dermally derived precursor cell. We show by lineage tracing that murine SKPs from dorsal skin originate from mesenchymal and not neural crest-derived cells. These mesenchymally derived SKPs can, without genetic manipulation, generate functional Schwann cells, a neural crest cell type, and are highly similar at the transcriptional level to Schwann cells isolated from the peripheral nerve. This is not a mouse-specific phenomenon, since human SKPs that are highly similar at the transcriptome level can be made from neural crest-derived facial and mesodermally derived foreskin dermis and the foreskin SKPs can make myelinating Schwann cells. Thus, nonneural crest-derived mesenchymal precursors can differentiate into bona fide peripheral glia in the absence of genetic manipulation, suggesting that developmentally defined lineage boundaries are more flexible than widely thought.

  7. Age-related changes in vertebral and iliac crest 3D bone microstructure--differences and similarities.

    Science.gov (United States)

    Thomsen, J S; Jensen, M V; Niklassen, A S; Ebbesen, E N; Brüel, A

    2015-01-01

    Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes. The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between the bone microstructure at these skeletal sites. Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19-96 years) and 39 men (23-95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified. For both women and men, bone volume per total volume (BV/TV), connectivity density (CD), and trabecular number (Tb.N) decreased significantly, while structure model index (SMI) and trabecular separation (Tb.Sp) increased significantly with age at either skeletal site. Vertebral trabecular thickness (Tb.Th) was independent of age for both women and men, while iliac Tb.Th decreased significantly with age for men, but not for women. In general, the vertebral and iliac age-related changes were similar. The 95th percentile of the Tb.Th distribution increased significantly with age for women but was independent of age for men at the vertebral body, while it was independent of age for either sex at the iliac crest. The Tb.Th probability density functions at the two skeletal sites became significantly more similar with age for women, but not for men. The microstructural parameters at the iliac crest and the vertebral bodies were only moderately correlated from r = 0.38 for SMI in women to r = 0.75 for Tb.Sp in men. Age-related changes in vertebral and iliac bone microstructure were in general similar. The iliac

  8. Safety and efficacy of an 8-week regimen of grazoprevir plus ruzasvir plus uprifosbuvir compared with grazoprevir plus elbasvir plus uprifosbuvir in participants without cirrhosis infected with hepatitis C virus genotypes 1, 2, or 3 (C-CREST-1 and C-CREST-2, part A)

    DEFF Research Database (Denmark)

    Gane, Edward J; Pianko, Stephen; Roberts, Stuart K

    2017-01-01

    BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprev...

  9. Iliac crest autograft versus alternative constructs for anterior cervical spine surgery: Pros, cons, and costs

    Science.gov (United States)

    Epstein, Nancy E.

    2012-01-01

    Background: Grafting choices available for performing anterior cervical diskectomy/fusion (ACDF) procedures have become a major concern for spinal surgeons, and their institutions. The “gold standard”, iliac crest autograft, may still be the best and least expensive grafting option; it deserves to be reassessed along with the pros, cons, and costs for alternative grafts/spacers. Methods: Although single or multilevel ACDF have utilized iliac crest autograft for decades, the implant industry now offers multiple alternative grafting and spacer devices; (allografts, cages, polyether-etherketone (PEEK) amongst others). While most studies have focused on fusion rates and clinical outcomes following ACDF, few have analyzed the “value-added” of these various constructs (e.g. safety/efficacy, risks/complications, costs). Results: The majority of studies document 95%-100% fusion rates when iliac crest autograft is utilized to perform single level ACDF (X-ray or CT confirmed at 6-12 postoperative months). Although many allograft studies similarly quote 90%-100% fusion rates (X-ray alone confirmed at 6-12 postoperative months), a recent “post hoc analysis of data from a prospective multicenter trial” (Riew KD et. al., CSRS Abstract Dec. 2011; unpublished) revealed a much higher delayed fusion rate using allografts at one year 55.7%, 2 years 87%, and four years 92%. Conclusion: Iliac crest autograft utilized for single or multilevel ACDF is associated with the highest fusion, lowest complication rates, and significantly lower costs compared with allograft, cages, PEEK, or other grafts. As spinal surgeons and institutions become more cost conscious, we will have to account for the “value added” of these increasingly expensive graft constructs. PMID:22905321

  10. Donor site complications in bone grafting: comparison of iliac crest, calvarial, and mandibular ramus bone.

    Science.gov (United States)

    Scheerlinck, Laura M E; Muradin, Marvick S M; van der Bilt, Andries; Meijer, Gert J; Koole, Ronald; Van Cann, Ellen M

    2013-01-01

    To compare the donor site complication rate and length of hospital stay following the harvest of bone from the iliac crest, calvarium, or mandibular ramus. Ninety-nine consecutively treated patients were included in this retrospective observational single-center study. Iliac crest bone was harvested in 55 patients, calvarial bone in 26 patients, and mandibular ramus bone in 18 patients. Harvesting of mandibular ramus bone was associated with the lowest percentages of major complications (5.6%), minor complications (22.2%), and total complications (27.8%). Harvesting of iliac crest bone was related to the highest percentages of minor complications (56.4%) and total complications (63.6%), whereas harvesting of calvarial bone induced the highest percentage of major complications (19.2%). The length of the hospital stay was significantly influenced by the choice of donor site (P = .003) and age (P = .009); young patients with the mandibular ramus as the donor site had the shortest hospital stay. Harvesting of mandibular ramus bone was associated with the lowest percentage of complications and the shortest hospital stay. When the amount of bone to be obtained is deemed sufficient, mandibular ramus bone should be the first choice for the reconstruction of maxillofacial defects.

  11. Heart rate variability and baroreflex sensitivity in bilateral lung transplant recipients.

    Science.gov (United States)

    Fontolliet, Timothée; Gianella, Pietro; Pichot, Vincent; Barthélémy, Jean-Claude; Gasche-Soccal, Paola; Ferretti, Guido; Lador, Frédéric

    2018-01-09

    The effects of lung afferents denervation on cardiovascular regulation can be assessed on bilateral lung transplantation patients. The high-frequency component of heart rate variability is known to be synchronous with breathing frequency. Then, if heart beat is neurally modulated by breathing frequency, we may expect disappearance of high frequency of heart rate variability in bilateral lung transplantation patients. On 11 patients and 11 matching healthy controls, we measured R-R interval (electrocardiography), blood pressure (Portapres ® ) and breathing frequency (ultrasonic device) in supine rest, during 10-min free breathing, 10-min cadenced breathing (0·25 Hz) and 5-min handgrip. We analysed heart rate variability and spontaneous variability of arterial blood pressure, by power spectral analysis, and baroreflex sensitivity, by the sequence method. Concerning heart rate variability, with respect to controls, transplant recipients had lower total power and lower low- and high-frequency power. The low-frequency/high-frequency ratio was higher. Concerning systolic, diastolic and mean arterial pressure variability, transplant recipients had lower total power (only for cadenced breathing), low frequency and low-frequency/high-frequency ratio during free and cadenced breathing. Baroreflex sensitivity was decreased. Denervated lungs induced strong heart rate variability reduction. The higher low-frequency/high-frequency ratio suggested that the total power drop was mostly due to high frequency. These results support the hypothesis that neural modulation from lung afferents contributes to the high frequency of heart rate variability. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  12. Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).

    Science.gov (United States)

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

    2017-07-01

    In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.

  13. A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

    International Nuclear Information System (INIS)

    Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M

    2006-01-01

    In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions

  14. A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

    Energy Technology Data Exchange (ETDEWEB)

    Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M [Signal and Imaging Processing and Tele-Medicine Technology Research Group, Department of Electrical and Electronics Engineering, Universiti Teknologi PETRONAS, 31750 Tronoh, Perak (Malaysia)

    2006-04-01

    In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

  15. Gastrointestinal and external parasites of the white-crested elaenia Elaenia albiceps chilensis (Aves, Tyrannidae in Chile

    Directory of Open Access Journals (Sweden)

    Danny Fuentes

    Full Text Available The objective of this study is to evaluate the ectoparasites and helminths of the white-crested elaenia, Elaenia albiceps chilensis. Feather mites Anisophyllodes elaeniae, Trouessartia elaeniae, and Analges sp. were detected in 51% of birds (n=106, whereas 24% were infected with lice (Tyranniphilopterus delicatulus, Menacanthus cfr. distinctus, and Ricinus cfr. invadens. Helminths Viguiera sp. and Capillaria sp. were found in five of the birds that were necropsied (n=20. With the exception of A. elaeniae, T. elaeniae, and T. delicatulus, all parasites represented new records found for the white-crested elaenia, and therefore for the Chilean repertoire of biodiversity.

  16. The murine homeobox gene Msx-3 shows highly restricted expression in the developing neural tube.

    Science.gov (United States)

    Shimeld, S M; McKay, I J; Sharpe, P T

    1996-04-01

    The mouse homeobox-genes Msx-1 and Msx-2 are expressed in several areas of the developing embryo, including the neural tube, neural crest, facial processes and limb buds. Here we report the characterisation of a third mouse Msx gene, which we designate Msx-3. The embryonic expression of Msx-3 was found to differ from that of Msx-1 and -2 in that it was confined to the dorsal neural tube. In embryos with 5-8 somites a segmental pattern of expression was observed in the hindbrain, with rhombomeres 3 and 5 lacking Msx-3 while other rhombomeres expressed Msx-3. This pattern was transient, however, such that in embryos with 18 or more somites expression was continuous throughout the dorsal hindbrain and anterior dorsal spinal cord. Differentiation of dorsal cell types in the neural tube can be induced by addition of members of the Tgf-beta family. Additionally, Msx-1 and -2 have been shown to be activated by addition of the Tgf-beta family member Bmp-4. To determine if Bmp-4 could activate Msx-3, we incubated embryonic hindbrain explants with exogenous Bmp-4. The dorsal expression of Msx-3 was seen to expand into more ventral regions of the neurectoderm in Bmp-4-treated cultures, implying that Bmp-4 may be able to mimic an in vivo signal that induces Msx-3.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-28

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

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

    Science.gov (United States)

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

    2017-04-05

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

  20. The Effect of Heart Rate on the Heart Rate Variability Response to Autonomic Interventions

    Directory of Open Access Journals (Sweden)

    George E Billman

    2013-08-01

    Full Text Available Heart rate variability (HRV, the beat-to-beat variation in either heart rate (HR or heart period (R-R interval, has become a popular clinical and investigational tool to quantify cardiac autonomic regulation. However, it is not widely appreciated that, due to the inverse curvilinear relationship between HR and R-R interval, HR per se can profoundly influence HRV. It is, therefore, critical to correct HRV for the prevailing HR particularly, as HR changes in response to autonomic neural activation or inhibition. The present study evaluated the effects of HR on the HRV response to autonomic interventions that either increased (submaximal exercise, n = 25 or baroreceptor reflex activation, n = 20 or reduced (pharmacological blockade: β-adrenergic receptor, muscarinic receptor antagonists alone and in combination, n = 25, or bilateral cervical vagotomy, n = 9 autonomic neural activity in a canine model. Both total (RR interval standard deviation, RRSD and the high frequency variability (HF, 0.2 to 1.04 Hz were determined before and in response to an autonomic intervention. All interventions that reduced or abolished cardiac parasympathetic regulation provoked large reductions in HRV even after HR correction [division by mean RRsec or (mean RRsec2 for RRSD and HF, respectively] while interventions that reduced HR yielded mixed results. β-adrenergic receptor blockade reduced HRV (RRSD but not HF while both RRSD and HF increased in response to increases in arterial blood (baroreceptor reflex activation even after HR correction. These data suggest that the physiological basis for HRV is revealed after correction for prevailing HR and, further, that cardiac parasympathetic activity is responsible for a major portion of the HRV in the dog.

  1. Sympathetic neural responses to smoking are age dependent

    Czech Academy of Sciences Publication Activity Database

    Hering, D.; Somers, V. K.; Kára, T.; Kucharska, W.; Jurák, Pavel; Bieniaszewski, L.; Narkiewicz, K.

    2006-01-01

    Roč. 24, č. 4 (2006), s. 691-695 ISSN 0263-6352 R&D Projects: GA ČR(CZ) GA102/05/0402 Institutional research plan: CEZ:AV0Z20650511 Keywords : sympathetic neural response * blood pressure * heart rate * smoking Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 4.021, year: 2006

  2. Central neural pathways for thermoregulation

    Science.gov (United States)

    Morrison, Shaun F.; Nakamura, Kazuhiro

    2010-01-01

    Central neural circuits orchestrate a homeostatic repertoire to maintain body temperature during environmental temperature challenges and to alter body temperature during the inflammatory response. This review summarizes the functional organization of the neural pathways through which cutaneous thermal receptors alter thermoregulatory effectors: the cutaneous circulation for heat loss, the brown adipose tissue, skeletal muscle and heart for thermogenesis and species-dependent mechanisms (sweating, panting and saliva spreading) for evaporative heat loss. These effectors are regulated by parallel but distinct, effector-specific neural pathways that share a common peripheral thermal sensory input. The thermal afferent circuits include cutaneous thermal receptors, spinal dorsal horn neurons and lateral parabrachial nucleus neurons projecting to the preoptic area to influence warm-sensitive, inhibitory output neurons which control thermogenesis-promoting neurons in the dorsomedial hypothalamus that project to premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, that descend to provide the excitation necessary to drive thermogenic thermal effectors. A distinct population of warm-sensitive preoptic neurons controls heat loss through an inhibitory input to raphe pallidus neurons controlling cutaneous vasoconstriction. PMID:21196160

  3. Multielement analysis of iliac crest bone by neutron activation

    International Nuclear Information System (INIS)

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

    2000-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  5. Brain-heart interactions: challenges and opportunities with functional magnetic resonance imaging at ultra-high field.

    Science.gov (United States)

    Chang, Catie; Raven, Erika P; Duyn, Jeff H

    2016-05-13

    Magnetic resonance imaging (MRI) at ultra-high field (UHF) strengths (7 T and above) offers unique opportunities for studying the human brain with increased spatial resolution, contrast and sensitivity. However, its reliability can be compromised by factors such as head motion, image distortion and non-neural fluctuations of the functional MRI signal. The objective of this review is to provide a critical discussion of the advantages and trade-offs associated with UHF imaging, focusing on the application to studying brain-heart interactions. We describe how UHF MRI may provide contrast and resolution benefits for measuring neural activity of regions involved in the control and mediation of autonomic processes, and in delineating such regions based on anatomical MRI contrast. Limitations arising from confounding signals are discussed, including challenges with distinguishing non-neural physiological effects from the neural signals of interest that reflect cardiorespiratory function. We also consider how recently developed data analysis techniques may be applied to high-field imaging data to uncover novel information about brain-heart interactions. © 2016 The Author(s).

  6. Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

    Science.gov (United States)

    Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

    2015-04-01

    To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

  7. Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.

    Science.gov (United States)

    Muralidharan, Pooja; Sarmah, Swapnalee; Zhou, Feng C; Marrs, James A

    2013-06-19

    Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

  8. Fetal Alcohol Spectrum Disorder (FASD Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    James A. Marrs

    2013-06-01

    Full Text Available Fetal alcohol spectrum disorder (FASD, caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.

  9. The novel mouse mutant, chuzhoi, has disruption of Ptk7 protein and exhibits defects in neural tube, heart and lung development and abnormal planar cell polarity in the ear

    Directory of Open Access Journals (Sweden)

    Paudyal Anju

    2010-08-01

    Full Text Available Abstract Background The planar cell polarity (PCP signalling pathway is fundamental to a number of key developmental events, including initiation of neural tube closure. Disruption of the PCP pathway causes the severe neural tube defect of craniorachischisis, in which almost the entire brain and spinal cord fails to close. Identification of mouse mutants with craniorachischisis has proven a powerful way of identifying molecules that are components or regulators of the PCP pathway. In addition, identification of an allelic series of mutants, including hypomorphs and neomorphs in addition to complete nulls, can provide novel genetic tools to help elucidate the function of the PCP proteins. Results We report the identification of a new N-ethyl-N-nitrosourea (ENU-induced mutant with craniorachischisis, which we have named chuzhoi (chz. We demonstrate that chuzhoi mutant embryos fail to undergo initiation of neural tube closure, and have characteristics consistent with defective convergent extension. These characteristics include a broadened midline and reduced rate of increase of their length-to-width ratio. In addition, we demonstrate disruption in the orientation of outer hair cells in the inner ear, and defects in heart and lung development in chuzhoi mutants. We demonstrate a genetic interaction between chuzhoi mutants and both Vangl2Lp and Celsr1Crsh mutants, strengthening the hypothesis that chuzhoi is involved in regulating the PCP pathway. We demonstrate that chuzhoi maps to Chromosome 17 and carries a splice site mutation in Ptk7. This mutation results in the insertion of three amino acids into the Ptk7 protein and causes disruption of Ptk7 protein expression in chuzhoi mutants. Conclusions The chuzhoi mutant provides an additional genetic resource to help investigate the developmental basis of several congenital abnormalities including neural tube, heart and lung defects and their relationship to disruption of PCP. The chuzhoi mutation

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

    Directory of Open Access Journals (Sweden)

    Susan Michele Bouchard

    2010-07-01

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

  11. SLUG (SNAI2) deletions in patients with Waardenburg disease.

    Science.gov (United States)

    Sánchez-Martín, Manuel; Rodríguez-García, Arancha; Pérez-Losada, Jesús; Sagrera, Ana; Read, Andrew P; Sánchez-García, Isidro

    2002-12-01

    Waardenburg syndrome (WS; deafness with pigmentary abnormalities) is a congenital disorder caused by defective function of the embryonic neural crest. Depending on additional symptoms, WS is classified into four types: WS1, WS2, WS3 and WS4. WS1 and WS3 are caused by mutations in PAX3, whereas WS2 is heterogenous, being caused by mutations in the microphthalmia (MITF) gene in some but not all affected families. The identification of Slugh, a zinc-finger transcription factor expressed in migratory neural crest cells, as the gene responsible for pigmentary disturbances in mice prompted us to analyse the role of its human homologue SLUG in neural crest defects. Here we show that two unrelated patients with WS2 have homozygous deletions in SLUG which result in absence of the SLUG product. We further show that Mitf is present in Slug-deficient cells and transactivates the SLUG promoter, and that Slugh and Kit genetically interact in vivo. Our findings further define the locus heterogeneity of WS2 and point to an essential role of SLUG in the development of neural crest-derived human cell lineages: its absence causes the auditory-pigmentary symptoms in at least some individuals with WS2.

  12. 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.

  13. Protocadherin PAPC is expressed in the CNC and can compensate for the loss of PCNS.

    Science.gov (United States)

    Schneider, Martina; Huang, Chaolie; Becker, Sarah F S; Gradl, Dietmar; Wedlich, Doris

    2014-02-01

    Protocadherins represent the biggest subgroup within the cadherin superfamily of transmembrane glycoproteins. In contrast to classical type I cadherins, protocadherins in general exhibit only moderate adhesive activity. During embryogenesis, they are involved in cell signaling and regulate diverse morphogenetic processes, including morphogenetic movements during gastrulation and neural crest migration. The two protocadherins paraxial protocadherin (PAPC) and axial protocadherin (AXPC) are indispensable for proper gastrulation movements in Xenopus and zebrafish. The closest relative PCNS instead, is required for neural crest and somite formation. Here, we show that cranial neural crest (CNC) cells in addition to PCNS express PAPC, but not AXPC. Overexpression of PAPC resulted in comparable migration defects as knockdown of PCNS. Moreover, reconstitution experiments revealed that PAPC is able to replace PCNS in CNC cells, indicating that both protocadherins can regulate CNC migration. Copyright © 2013 Wiley Periodicals, Inc.

  14. Glutamate transporter type 3 knockout leads to decreased heart rate possibly via parasympathetic mechanism

    OpenAIRE

    Deng, Jiao; Li, Jiejie; Li, Liaoliao; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

    2013-01-01

    Parasympathetic tone is a dominant neural regulator for basal heart rate. Glutamate transporters (EAAT) via their glutamate uptake functions regulate glutamate neurotransmission in the central nervous system. We showed that EAAT type 3 (EAAT3) knockout mice had a slower heart rate than wild-type mice when they were anesthetized. We design this study to determine whether non-anesthetized EAAT3 knockout mice have a slower heart rate and, if so, what may be the mechanism for this effect. Young a...

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

    Directory of Open Access Journals (Sweden)

    Elisabeth Findlay

    2008-12-01

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

  16. CREST biorepository for translational studies on malignant mesothelioma, lung cancer and other respiratory tract diseases: Informatics infrastructure and standardized annotation.

    Science.gov (United States)

    Ugolini, Donatella; Neri, Monica; Bennati, Luca; Canessa, Pier Aldo; Casanova, Georgia; Lando, Cecilia; Leoncini, Giacomo; Marroni, Paola; Parodi, Barbara; Simonassi, Claudio; Bonassi, Stefano

    2012-03-01

    Advances in molecular epidemiology and translational research have led to the need for biospecimen collection. The Cancer of the Respiratory Tract (CREST) biorepository is concerned with pleural malignant mesothelioma (MM) and lung cancer (LC). The biorepository staff has collected demographic and epidemiological data directly from consenting subjects using a structured questionnaire, in agreement with The Public Population Project in Genomics (P(3)G). Clinical and follow-up data were collected. Sample data were also recorded. The architecture is based on a database designed with Microsoft Access. Data standardization was carried out to conform with established conventions or procedures. As from January 31, 2011, the overall number of recruited subjects was 1,857 (454 LC, 245 MM, 130 other cancers and 1,028 controls). Due to its infrastructure, CREST was able to join international projects, sharing samples and/or data with other research groups in the field. The data management system allows CREST to be involved, through a minimum data set, in the national project for the construction of the Italian network of Oncologic BioBanks (RIBBO), and in the infrastructure of a pan-European biobank network (BBMRI). The CREST biorepository is a valuable tool for translational studies on respiratory tract diseases, because of its simple and efficient infrastructure.

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

    Science.gov (United States)

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

    2017-07-01

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

  18. Complications encountered in patients bearers with crest syndrome in rheumatological service of the Hospital San Juan de Dios until September 2009

    International Nuclear Information System (INIS)

    Mendez Rodriguez, Alexis

    2010-01-01

    Systematic sclerosis is a disease that has caused much morbidity and dependence in patients. Despite not being the disease most prevalent in rheumatological practice, it has been perhaps one that has generated more interest in the complex pathophysiology; but, also a great sense of frustration with the great therapeutic limitations especially when is diagnosed in advanced stages. The research was conducted in order to motivate early clinical search of the major complications found in patients CREST syndrome, in rheumatological service of the Hospital San Juan de Dios until September 2009 the total of cases with a diagnosis of CREST were reviewed in outpatient records, the study population have been of 41 patients. The different clinical manifestations of the patient were taken into account, among other aspects: immunological studies, established treatments and diagnosis methods as conventional radiology, endoscopic studies, echocardiogram, capillaroscopy. This job has determined among other things, that the majority of patients with CREST come from Desamparados and the Southern Zone, representing 31.7 and 29.2%, respectively, 98% are women and 76% of patients engaged in domestic chores and no mortality case was found in relation to CREST [es

  19. Ganglioneuroma: an 'incidentaloma' of childhood

    International Nuclear Information System (INIS)

    Schulman, H.; Laufer, L.; Barki, Y.; Hertzanu, Y.; Philip, M.; Mares, A.J.; Maor, E.

    1998-01-01

    In adults clinically silent adrenal masses can be discovered incidentally in imaging studies. Most of these 'incidentalomas' are benign, non-functioning adenomas. In contradistinction, in infancy and childhood the most common adrenal mass is the neuroblastoma, a malignant neural crest tumour. Four children are described, each with a benign neural crest tumour - ganglioneuroma -incidentally discovered by conventional radiography or sonographic examination. Complete surgical excision resulted in total recovery of all the children. (orig.)

  20. Epigenetic control of skull morphogenesis by histone deacetylase 8

    OpenAIRE

    Haberland, Michael; Mokalled, Mayssa H.; Montgomery, Rusty L.; Olson, Eric N.

    2009-01-01

    Histone deacetylases (Hdacs) are transcriptional repressors with crucial roles in mammalian development. Here we provide evidence that Hdac8 specifically controls patterning of the skull by repressing a subset of transcription factors in cranial neural crest cells. Global deletion of Hdac8 in mice leads to perinatal lethality due to skull instability, and this is phenocopied by conditional deletion of Hdac8 in cranial neural crest cells. Hdac8 specifically represses the aberrant expression of...

  1. Pheochromocytoma and paraganglioma

    International Nuclear Information System (INIS)

    Reckova, M.

    2013-01-01

    Pheochromocytoma and paraganglioma are rare tumors that originate from the cells of neural crest. Despite a wide variety of clinical features, the main remains the hypertension. Most of pheochromocytoma (FEO) and paraganglioma (PGL) represent sporadic tumors but about 20-30% of these tumors are familial. Besides standard imagining techniques, functional diagnostics plays important role, as well. The definitive treatment is surgical therapy, however in inoperable cases, radionuclide therapeutic methods are used. Systemic chemotherapy has only limited efficacy and, currently, targeted therapeutic approaches are studied. External-beam radiotherapy is used in palliative settings. The most frequent causes of morbidity and mortality are cardiovascular events, such as sudden death, heart attack, heart failure and cerebrovascular events. Early diagnosis is very important not just for prevention of disease dissemination, but for the prevention of possible complications, as well. (author)

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

    Science.gov (United States)

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

  3. Linear and nonlinear ARMA model parameter estimation using an artificial neural network

    Science.gov (United States)

    Chon, K. H.; Cohen, R. J.

    1997-01-01

    This paper addresses parametric system identification of linear and nonlinear dynamic systems by analysis of the input and output signals. Specifically, we investigate the relationship between estimation of the system using a feedforward neural network model and estimation of the system by use of linear and nonlinear autoregressive moving-average (ARMA) models. By utilizing a neural network model incorporating a polynomial activation function, we show the equivalence of the artificial neural network to the linear and nonlinear ARMA models. We compare the parameterization of the estimated system using the neural network and ARMA approaches by utilizing data generated by means of computer simulations. Specifically, we show that the parameters of a simulated ARMA system can be obtained from the neural network analysis of the simulated data or by conventional least squares ARMA analysis. The feasibility of applying neural networks with polynomial activation functions to the analysis of experimental data is explored by application to measurements of heart rate (HR) and instantaneous lung volume (ILV) fluctuations.

  4. 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

  5. Bone thickness of the infrazygomatic crest area in skeletal Class III growing patients: A computed tomographic study

    International Nuclear Information System (INIS)

    Lee, Hyub Soo; Choi, Hang Moon; Choi, Dong Soon; Jang, Insan; Cha, Bong Kuen

    2013-01-01

    This study was performed to investigate the bone thickness of the infrazygomatic crest area by computed tomography (CT) for placement of a miniplate as skeletal anchorage for maxillary protraction in skeletal Class III children. CT images of skeletal Class III children (7 boys, 9 girls, mean age: 11.4 years) were taken parallel to the Frankfurt horizontal plane. The bone thickness of the infrazygomatic crest area was measured at 35 locations on the right and left sides, perpendicular to the bone surface. The bone was thickest (5.0 mm) in the upper zygomatic bone and thinnest (1.1 mm) in the anterior wall of the maxillary sinus. Generally, there was a tendency for the bone to be thicker at the superior and lateral area of the zygomatic process of the maxilla. There was no clinically significant difference in bone thickness between the right and left sides; however, it was thicker in male than in female subjects. In the infrazygomatic crest area, the superior and lateral area of the zygomatic process of the maxilla had the most appropriate thickness for placement of a miniplate in growing skeletal Class III children with a retruded maxilla.

  6. Bone thickness of the infrazygomatic crest area in skeletal Class III growing patients: A computed tomographic study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyub Soo; Choi, Hang Moon; Choi, Dong Soon; Jang, Insan; Cha, Bong Kuen [College of Dentistry and Research Institute of Oral Science, Gangneung-Wonju National University, Gangneung (Korea, Republic of)

    2013-12-15

    This study was performed to investigate the bone thickness of the infrazygomatic crest area by computed tomography (CT) for placement of a miniplate as skeletal anchorage for maxillary protraction in skeletal Class III children. CT images of skeletal Class III children (7 boys, 9 girls, mean age: 11.4 years) were taken parallel to the Frankfurt horizontal plane. The bone thickness of the infrazygomatic crest area was measured at 35 locations on the right and left sides, perpendicular to the bone surface. The bone was thickest (5.0 mm) in the upper zygomatic bone and thinnest (1.1 mm) in the anterior wall of the maxillary sinus. Generally, there was a tendency for the bone to be thicker at the superior and lateral area of the zygomatic process of the maxilla. There was no clinically significant difference in bone thickness between the right and left sides; however, it was thicker in male than in female subjects. In the infrazygomatic crest area, the superior and lateral area of the zygomatic process of the maxilla had the most appropriate thickness for placement of a miniplate in growing skeletal Class III children with a retruded maxilla.

  7. Comparative anatomy and osteohistology of hyperelongate neural spines in the sphenacodontids Sphenacodon and Dimetrodon (Amniota: Synapsida).

    Science.gov (United States)

    Huttenlocker, Adam K; Rega, Elizabeth; Sumida, Stuart S

    2010-12-01

    Osteohistological investigations of hyperelongate vertebral spinous processes (neural spines) are presented to elucidate previously unknown aspects of dorsal sail form and function in two, closely related genera of "sail-backed" synapsids: Sphenacodon and Dimetrodon. Although recent and classic surveys of bone histology in extinct vertebrates have sampled the genus Dimetrodon, new sectioning of Sphenacodon material allows a comparative analysis of these structures among Sphenacodontidae for the first time. Variability within the histological organization of the neural spine is assessed by examining multiple regions along its length, and implications for soft tissue correlates, growth and mechanics are considered here. Both genera exhibit extensive parallel-fibered and fibrolamellar bone, in addition to lamellar bone. Several features vary along the length of the spine in each species. Muscle scars and extensive Sharpey's fibers are present at the base of the spine; no scars and fewer fibers are manifested ∼55-60 mm above the zygapophyses in mature individuals. The distal cortex of the spine does not exhibit greater vascularity than the proximal region in either genus. However, both genera manifest distinct vascular grooves of variable size along the distal periosteal surface, some of which become incorporated into the distal cortex. The observed histovariability appears to record the transition from the proximal (epaxial muscle embedded) to the distally protruding portion of the spine. These observations and independent pathological evidence support the existence of a short dorsal crest in Sphenacodon and possibly other basal sphenacodontids. Although the thermoregulatory capacity of such a crest remains uncertain, developmental and mechanical features are readily interpretable and are discussed with respect to the origins and early evolution of the dorsal sail in sphenacodontid synapsids. © 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

    2010-10-01

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

  9. EDITORIAL: Focus on Heart and Mind

    Science.gov (United States)

    Bodenschatz, Eberhard; Wolf, Fred

    2008-01-01

    Among the organs of our body, the function of heart and brain are unique in that their operation emerges from the collective dynamics of millions of strongly interacting cells well organized in their geometrical structure and connectivity. In the heart muscle the propagation of a nonlinear wave pulse, the cardiac action potential, controls the contraction. Usually the propagation is well-organized both in space and time and the heart functions as an efficient biological pump. Instabilities triggered by diseased tissue but also by dynamical heterogeneities, may, however, induce cardiac arrhythmia and fibrillation, where the pacemaker looses control to dynamically generated, high-frequency self-excitation of the muscle. In this state the coherence of contraction is lost and may lead within minutes to death. The appearance of arrhythmias can be associated with topological singularities, the so called spiral or scroll waves, and how the occurrence of this malfunctioning pattern-formation process can be understood is a dominant subject of current research. This is all the more important as cardiac arrhythmias and fibrillation are the main cause of premature death in the developed world. Similarly, in the brain the propagation of a nonlinear wave pulse, namely the neural action potential, is at the basis of the computational and memory power of the brain, i.e. what determines the workings of our 'minds'. Here, however, due to the high degree of interconnectivity and topological complexity of the neuronal network, the coordinated activity of millions of interacting nerve cells is more complex, although the basic principles of action potential generation at the level of each cell are quite similar. The currently emerging field of network dynamical systems is largely driven by the mathematical challenge and the steady stream of novel dynamical phenomena that results from the interplay of local nonlinear dynamics and complex network structure in models of biological neuronal

  10. Hearts and minds.

    Science.gov (United States)

    Naylor, A R

    2012-01-01

    The American Heart Association liberalised guidelines for carotid stenting (CAS) into average risk patients based on the following interpretations and assumptions; (i) CAS doubles the risk of procedural stroke; (ii) CEA doubles the risk of procedural myocardial infarction (MI); (iii) peri-operative MI significantly reduces long-term survival; (iv) poorer long-term survival is attributable to a greater proportion of CEA patients dying after their peri-operative MI. (v) reduced survival in CEA patients suffering a peri-operative MI offsets any benefit conferred by the lower procedural stroke risk so that; (vi) CAS is considered equivalent to CEA and may even be safer in those considered high risk for procedural MI. However, this much publicised rationale is flawed by the simple fact that the poorer survival rates observed in CREST were not attributable to a greater proportion of CEA patients dying following their procedural MI. In fact, a relatively higher proportion of CAS patients suffering a peri-operative MI died during follow-up. This observation changes how the literature should be interpreted. The clinical reality is that up to 10% of patients will suffer a stroke within seven days of their index TIA and the benefits of intervening in the hyperacute period after onset of symptoms (ie offering greater stroke prevention) will far outweigh any potential consequences of peri-operative MI and reduced life expectancy. Peri-operative MI should inform, but not drive the current debate. More importantly, it should not deflect attention away from the most important management priority; the prevention of stroke. This is one situation where the heart should not rule the head! Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  11. [Head and neck paragangliomas. Embryological origin and anatomical characteristics: topographic distribution and vascularization pattern].

    Science.gov (United States)

    Carretero González, José; Blanco Pérez, Pedro; Vázquez Osorio, María Teresa; Benito González, Fernando; Sañudo Tejedo, José Ramón

    2009-02-01

    Paragangliomas are tumors that arise in the extraadrenal paraganglia and result from migration of neural crest cells during embryonic development. Based on their anatomical distribution, innervation and microscopic structure, these tumors can be classified into interrelated families: branchiomeric paraganglia (related to the branchial clefts and arches), intravagal, aortic-sympathetic and visceral-autonomic. Head and neck paragangliomas belong mainly to the first two of these families. The present article is divided into two parts. The first part reviews the embryological origin of these tumors. Special emphasis is placed on the process of neurulation or neural tube formation, neurosegmentation (with a summary of the mechanisms involved in the initial segmentation of the neural tube and of the hindbrain and spinal medulla), and the development of the sensory placodes and secondary inductions in the cranial region. Subsequently, the neural crest is analyzed, with special attention paid to the cranial neural crest. The embryonogenesis of paragangliomas is also described. The second part describes the topographical distribution of head and neck paragangliomas according to their localization: jugulotympanic, orbit, intercarotid, subclavian and laryngeal. The embryonogenesis and most important anatomical characteristics are described for each type.

  12. A probablistic neural network classification system for signal and image processing

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, B. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    The Acoustical Heart Valve Analysis Package is a system for signal and image processing and classification. It is being developed in both Matlab and C, to provide an interactive, interpreted environment, and has been optimized for large scale matrix operations. It has been used successfully to classify acoustic signals from implanted prosthetic heart valves in human patients, and will be integrated into a commercial Heart Valve Screening Center. The system uses several standard signal processing algorithms, as well as supervised learning techniques using the probabilistic neural network (PNN). Although currently used for the acoustic heart valve application, the algorithms and modular design allow it to be used for other applications, as well. We will describe the signal classification system, and show results from a set of test valves.

  13. Retrospective radiographic study of marginal bone changes of 88 implants placed with split crest technique in the maxillary latero-posterior area

    Directory of Open Access Journals (Sweden)

    S. Longoni

    2016-04-01

    Full Text Available Aim This article presents a retrospective study on the behavior of implants placed with split crest technique in lateroposterior maxillary class IV atrophy. Materials and Methods Subjects who underwent implant placement following split crest technique in the maxillary latero-posterior area were enrolled in the present retrospective study. After a mean period of 6.2 years of function implant survival and success rates were assessed. Moreover, radiographic examination was made on digital periapical radiographs and by means of a specific software. Bone level changes were measured as the difference between the peri-implants crestal bone level and the implants shoulder during the last patient’s visit recall examination. Results A total of 30 patients satisfied the inclusion criteria and were included in the study; the subjects were treated with 88 implants (64 transmucosal and 24 submerged. The observation period for all patients treated with split crest technique varied between 4 and 8 years (mean 6.2 years. The implants survival rate was 96.6% and the prostheses survival rate was 100%. Bone resorption ranged between 2.3 mm and 2.7 mm. Conclusion Implants inserted in conjunction with split crest technique seems to be a promising therapy with similar results as conventional implant surgery.

  14. 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.

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

    Science.gov (United States)

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

    2013-08-01

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

  16. Discharge coefficient of a rectangular sharp-edged broad-crested weir

    OpenAIRE

    Zachoval Zbyněk; Knéblová Michaela; Roušar Ladislav; Rumann Ján; Šulc Jan

    2014-01-01

    his paper is concerned with the determination of the relationship for the calculation of the discharge coefficient at free overflow over a rectangular sharp-edged broad-crested weir without lateral contraction. The determination was made on the basis of new measurement in a range of the relative thickness of the weir from 0.12 to 0.30 and newly in a large range of relative height of the weir extremely from 0.24 to 6.8 which greatly expands the application possibilities of low weirs. In additi...

  17. REVIEW OF HEART DISEASE PREDICTION SYSTEM USING DATA MINING AND HYBRID INTELLIGENT TECHNIQUES

    Directory of Open Access Journals (Sweden)

    R. Chitra

    2013-07-01

    Full Text Available The Healthcare industry generally clinical diagnosis is done mostly by doctor’s expertise and experience. Computer Aided Decision Support System plays a major role in medical field. With the growing research on heart disease predicting system, it has become important to categories the research outcomes and provides readers with an overview of the existing heart disease prediction techniques in each category. Neural Networks are one of many data mining analytical tools that can be utilized to make predictions for medical data. From the study it is observed that Hybrid Intelligent Algorithm improves the accuracy of the heart disease prediction system. The commonly used techniques for Heart Disease Prediction and their complexities are summarized in this paper.

  18. 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

  19. 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

  20. Clinical effectiveness of 99mTc-diphosphonate scintigraphy of revascularized iliac crest flaps

    International Nuclear Information System (INIS)

    Smeele, L.E.; Hoekstra, O.S.; Winters, H.A.H.; Leemans, C.R.

    1996-01-01

    Clinical assessment of the perfusion of the musculocutaneous portion of composite iliac crest free flaps was compared to 99m Tc-diphosphonate (HDP) uptake in 14 patients who underwent primary oromandibular reconstruction after ablative cancer surgery. Bone scanning was performed on average at the 9-10th postoperative day (range 4-48) 3 h after intravenous injection of 550 MBq 99m Tc-HDP. Eleven patients showed complete concordance between 99m Tc-HDP uptake and soft-tissue status. Two patients showed uptake and viable muscle in spite of necrotic skin. One patient had a viable musculocutaneous flap but a photopenic defect in the bone graft; 6 months later, a small corresponding part of the bone was sequestrated. In this study, bone scanning and clinical assessment of muscle perfusion were 100% accurate in predicting viability of bone graft. Skin viability was a less reliable parameter. It is concluded that bone scanning is not indicated as routine investigation for revascularized iliac crest flaps and that clinical assessment of muscle perfusion is a reliable monitor of the early function of such flaps. (au) 8 refs

  1. Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos.

    Science.gov (United States)

    Zhang, Ting; Zhou, Xin-Ying; Ma, Xu-Fa; Liu, Jing-Xia

    2015-10-01

    Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. VIP secreting tumours in infancy

    International Nuclear Information System (INIS)

    Davies, R.P.; Slavotinek, J.P.; Dorney, S.F.A.

    1990-01-01

    Vasoactive intestinal polypeptide (VIP) secreting neural crest tumours are an uncommon but important treatable cause of intractable childhood diarrhoea. The radiological appearances of two cases are presented with a review of radiological findings in childhood VIP secreting neural crest tumours. Twenty eight cases of childhood VIP secreting neural crest tumours were reviewed. Nineteen (68%) were ganglioneuroblastomas and nine (32%) were ganglioneuromas. The majority of tumours (66%) were in a paravertebral location in the abdomen indicating that a search for such a tumour should be initiated at this site. Eighteen of the twenty eight cases reviewed discussed relevant radiological investigations. Calcification was detected in 50% of abdominal radiographs. Gut dilatation was often a prominent feature. A mass was detected in 5 of 5 cases where ultrasound findings were reported, and seven of seven cases with CT findings reported. Prior to the availability of CT and ultrasound the most useful investigation was IVU which demonstrated evidence of a mass in 5 of 9 cases. The presence of paravertebral calcification and gut dilatation on the plain radiograph of a child with intractable diarrhoea suggests the presence of a VIP secreting neural crest tumour. If an abdominal tumour is not found in the appropriate clinical setting and VIP levels are elevated, a widespread search of the paravertebral region is indicated. (orig.)

  3. Biological responses of Crested and Least auklets to volcanic destruction of nesting habitat in the Aleutian Islands, Alaska

    Science.gov (United States)

    Drew, Gary S.; Piatt, John F.; Williams, Jeffrey C.

    2018-01-01

    Crested Auklets (Aethia cristatella) and Least Auklets (A. pusilla) are crevice-nesting birds that breed in large mixed colonies at relatively few sites in the Aleutian Island archipelago, Bering Sea, Gulf of Alaska, and Sea of Okhotsk. Many of these colonies are located on active volcanic islands. The eruption of Kasatochi volcano, in the central Aleutians, on August 7, 2008, completely buried all crevice-nesting seabird habitat on the island. This provided an opportunity to examine the response of a large, mixed auklet colony to a major geological disturbance. Time-lapse imagery of nesting habitat indicated that both species returned to the largest pre-eruption colony site for several years, but subsequently abandoned it within 5 yr after the eruption. In 2010, a rockfall site in a cove north of the old colony site began to accumulate talus, and groups of auklets were observed using the site in 2011. Use of the new colony appeared to coincide with the abandonment of the old colony site by both species, though surface counts suggested that Least Auklets shifted to the new colony sooner than Crested Auklets. At-sea surveys of seabirds before and after the eruption indicated that both Crested and Least auklets shifted their at-sea distributions from the waters around Kasatochi Island to nearby Koniuji Island. In combination, at-sea counts and colony time-lapse imagery indicated that Crested and Least auklets using Kasatochi responded to the volcanic disturbance and complete loss of nesting habitat at the main colony on Kasatochi with dispersal either to newly created habitat on Kasatochi or to an alternate colony on a nearby island.

  4. Arteriovenous fistula of the superior gluteal artery as a complication of posterior iliac crest bone graft harvesting: 3D-CT angiography and arterial embolization

    OpenAIRE

    Kong, Chae-Gwan; Park, Jong-Beom; Won, Yoo-Dong; Riew, K. Daniel

    2009-01-01

    Superior gluteal artery injuries are rare, but potentially serious complications that occur during posterior iliac crest bone graft harvesting. The authors reported an arteriovenous fistula of the superior gluteal artery, which occurred as a complication during posterior iliac crest bone graft harvesting and was diagnosed with 3D-CT angiography, then treated with arterial embolization.

  5. The assessment of neural injury following open heart surgery by physiological tremor analysis.

    Science.gov (United States)

    Németh, Adám; Hejjel, László; Ajtay, Zénó; Kellényi, Lóránd; Solymos, Andor; Bártfai, Imre; Kovács, Norbert; Lenkey, Zsófia; Cziráki, Attila; Szabados, Sándor

    2013-02-21

    The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor. We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3(rd) to 5(th) post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test. We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p open heart surgery.

  6. Uncovering the Role of BMP Signaling in Melanocyte Development and Melanoma Tumorigenesis

    Science.gov (United States)

    2016-09-01

    specifiers’, genes that are initially expressed broadly in the neural crest and help to maintain neural crest identity (Fig. 2G ) (6). As development...melanoma cells, GDF6 and the BMP pathway negatively regulated SOX9 expression (Fig. 3G ; Fig. S13A-C). Epistasis analyses showed that SOX9 knockdown rescued...criteria, if the tumor volume reached >1,000 mm3; if tumor size or location affected the mobility or general health of animal, the animal was euthanized

  7. Evaluation of MODIS Land Surface Temperature with In Situ Snow Surface Temperature from CREST-SAFE

    Science.gov (United States)

    Perez Diaz, C. L.; Lakhankar, T.; Romanov, P.; Munoz, J.; Khanbilvardi, R.; Yu, Y.

    2016-12-01

    This paper presents the procedure and results of a temperature-based validation approach for the Moderate Resolution Imaging Spectroradiometer (MODIS) Land Surface Temperature (LST) product provided by the National Aeronautics and Space Administration (NASA) Terra and Aqua Earth Observing System satellites using in situ LST observations recorded at the Cooperative Remote Sensing Science and Technology Center - Snow Analysis and Field Experiment (CREST-SAFE) during the years of 2013 (January-April) and 2014 (February-April). A total of 314 day and night clear-sky thermal images, acquired by the Terra and Aqua satellites, were processed and compared to ground-truth data from CREST-SAFE with a frequency of one measurement every 3 min. Additionally, this investigation incorporated supplementary analyses using meteorological CREST-SAFE in situ variables (i.e. wind speed, cloud cover, incoming solar radiation) to study their effects on in situ snow surface temperature (T-skin) and T-air. Furthermore, a single pixel (1km2) and several spatially averaged pixels were used for satellite LST validation by increasing the MODIS window size to 5x5, 9x9, and 25x25 windows for comparison. Several trends in the MODIS LST data were observed, including the underestimation of daytime values and nighttime values. Results indicate that, although all the data sets (Terra and Aqua, diurnal and nocturnal) showed high correlation with ground measurements, day values yielded slightly higher accuracy ( 1°C), both suggesting that MODIS LST retrievals are reliable for similar land cover classes and atmospheric conditions. Results from the CREST-SAFE in situ variables' analyses indicate that T-air is commonly higher than T-skin, and that a lack of cloud cover results in: lower T-skin and higher T-air minus T-skin difference (T-diff). Additionally, the study revealed that T-diff is inversely proportional to cloud cover, wind speed, and incoming solar radiation. Increasing the MODIS window size

  8. 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...

  9. 77 FR 47628 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting...

    Science.gov (United States)

    2012-08-09

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

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

    Science.gov (United States)

    2011-04-21

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

  11. Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

    Directory of Open Access Journals (Sweden)

    Douglas Blackiston

    2011-01-01

    Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.

  12. ECG Based Heart Arrhythmia Detection Using Wavelet Coherence and Bat Algorithm

    Science.gov (United States)

    Kora, Padmavathi; Sri Rama Krishna, K.

    2016-12-01

    Atrial fibrillation (AF) is a type of heart abnormality, during the AF electrical discharges in the atrium are rapid, results in abnormal heart beat. The morphology of ECG changes due to the abnormalities in the heart. This paper consists of three major steps for the detection of heart diseases: signal pre-processing, feature extraction and classification. Feature extraction is the key process in detecting the heart abnormality. Most of the ECG detection systems depend on the time domain features for cardiac signal classification. In this paper we proposed a wavelet coherence (WTC) technique for ECG signal analysis. The WTC calculates the similarity between two waveforms in frequency domain. Parameters extracted from WTC function is used as the features of the ECG signal. These features are optimized using Bat algorithm. The Levenberg Marquardt neural network classifier is used to classify the optimized features. The performance of the classifier can be improved with the optimized features.

  13. Progress towards a measurement of the UHE cosmic ray electron flux using the CREST Instrument

    Science.gov (United States)

    Musser, Jim; Wakely, Scott; Coutu, Stephane; Geske, Matthew; Nutter, Scott; Tarle, Gregory; Park, Nahee; Schubnell, Michael; Gennaro, Joseph; Muller, Dietrich

    2012-07-01

    Electrons of energy beyond about 3 TeV have never been detected in the flux of cosmic rays at Earth despite strong evidence of their presence in a number of supernova remnants (e.g., SN 1006). The detection of high energy electrons at Earth would be extremely significant, yielding information about the spatial distribution of nearby cosmic ray sources. With the Cosmic Ray Electron Synchrotron Telescope (CREST), our collaboration has adopted a novel approach to the detection of electrons of energies between 2 and 50 TeV which results in a substantial increase in the acceptance and sensitivity of the apparatus relative to its physics size. The first LDB flight of the CREST detector took place in January 2012, with a float duration of approximately 10 days. In this paper we describe the flight performance of the instrument, and progress in the analysis of the data obtained in this flight.

  14. Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control.

    Science.gov (United States)

    Ardell, Jeffrey L; Nier, Heath; Hammer, Matthew; Southerland, E Marie; Ardell, Christopher L; Beaumont, Eric; KenKnight, Bruce H; Armour, J Andrew

    2017-11-15

    The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the

  15. Neural Responses to Heartbeats in the Default Network Encode the Self in Spontaneous Thoughts

    Science.gov (United States)

    Babo-Rebelo, Mariana; Richter, Craig G.

    2016-01-01

    The default network (DN) has been consistently associated with self-related cognition, but also to bodily state monitoring and autonomic regulation. We hypothesized that these two seemingly disparate functional roles of the DN are functionally coupled, in line with theories proposing that selfhood is grounded in the neural monitoring of internal organs, such as the heart. We measured with magnetoencephalograhy neural responses evoked by heartbeats while human participants freely mind-wandered. When interrupted by a visual stimulus at random intervals, participants scored the self-relatedness of the interrupted thought. They evaluated their involvement as the first-person perspective subject or agent in the thought (“I”), and on another scale to what degree they were thinking about themselves (“Me”). During the interrupted thought, neural responses to heartbeats in two regions of the DN, the ventral precuneus and the ventromedial prefrontal cortex, covaried, respectively, with the “I” and the “Me” dimensions of the self, even at the single-trial level. No covariation between self-relatedness and peripheral autonomic measures (heart rate, heart rate variability, pupil diameter, electrodermal activity, respiration rate, and phase) or alpha power was observed. Our results reveal a direct link between selfhood and neural responses to heartbeats in the DN and thus directly support theories grounding selfhood in the neural monitoring of visceral inputs. More generally, the tight functional coupling between self-related processing and cardiac monitoring observed here implies that, even in the absence of measured changes in peripheral bodily measures, physiological and cognitive functions have to be considered jointly in the DN. SIGNIFICANCE STATEMENT The default network (DN) has been consistently associated with self-processing but also with autonomic regulation. We hypothesized that these two functions could be functionally coupled in the DN, inspired by

  16. 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

  17. On the elementary neural forms of interaction rituals

    DEFF Research Database (Denmark)

    Heinskou, Marie Bruvik; Liebst, Lasse Suonperä

    Randall Collins’ interaction ritual (IR) theory suggests solidarity as neurologically hardwired in the capacity for rhythmic entrainment. Yet, this article suggests that IR theory may benefit from being tied more firmly to recent neurological research, specifically Stephen W. Porges......’ neurophysiological polyvagal theory. IR theory does not sufficiently acknowledge the autonomic nervous system as a system involving a phylogenetically ordered response hierarchy, of which only one subsystem supports prosocial behavior. The ritual ingredients of shared attention and mood may be clarified as part...... of a social engagement system, neurally regulating attention and arousal via brain-face-heart circuits. This allows rhythmic entrainment to be specified as a neural epiphenomenon of the social engagement system. The polyvagal perspective, moreover, challenges IR theory to reconsider the importance...

  18. Endogenous Natural Complement Inhibitor Regulates Cardiac Development

    DEFF Research Database (Denmark)

    Mortensen, Simon A; Skov, Louise L; Kjaer-Sorensen, Kasper

    2017-01-01

    mechanisms during fetal development and adult homeostasis. In this article, we describe the function of an endogenous complement inhibitor, mannan-binding lectin (MBL)-associated protein (MAp)44, in regulating the composition of a serine protease-pattern recognition receptor complex, MBL-associated serine...... of MAp44 caused impaired cardiogenesis, lowered heart rate, and decreased cardiac output. These defects were associated with aberrant neural crest cell behavior. We found that MAp44 competed with MASP-3 for pattern recognition molecule interaction, and knockdown of endogenous MAp44 expression could...... be rescued by overexpression of wild-type MAp44. Our observations provide evidence that immune molecules are centrally involved in the orchestration of cardiac tissue development....

  19. Investigating the Longer-Term Impact of the CREST Inquiry-Based Learning Programme on Student Self-regulated Processes and Related Motivations: Views of Students and Teachers

    Science.gov (United States)

    Moote, Julie

    2017-07-01

    This study investigates the impact of participation in the CREativity in Science and Technology (CREST) programme on student self-regulated processes and related motivations. The CREST scheme, a student-run science project managed by the British Science Association, is currently being implemented in schools across the UK to increase student engagement and motivation in science. Through implementing a rigorous quasi-experimental research design using two intervention conditions and one control group with immediate as well as 3-month delayed post-test data, the results documented both the immediate and longer-term positive impact of CREST participation on students' self-reported levels of self-regulation. The present study also investigates changes in teachers' perceptions of students' self-regulated learning through CREST programme participation. Group differences regarding changes in student self-reported self-regulation were not matched when looking at the teacher-reported self-regulated learning results at both immediate post-test and delayed post-test. These discrepancies are discussed in relation to analyses conducted on the other motivational constructs measured.

  20. A population of human brain cells expressing phenotypic markers of more than one lineage can be induced in vitro to differentiate into mesenchymal cells

    International Nuclear Information System (INIS)

    Rieske, Piotr; Augelli, Brian J.; Stawski, Robert; Gaughan, John; Azizi, S. Ausim; Krynska, Barbara

    2009-01-01

    Proliferating astrocytic cells from germinal, as well as mature areas of brain parenchyma, have the characteristics of neural stem/progenitor cells and are capable of generating both neurons and glia. We previously reported that primary fetal human brain cells, designated as Normal Human Astrocytes (NHA), expressed, in addition to GFAP, Vimentin and Nestin, low levels of βIII-Tubulin, an early neuronal marker, and differentiated into neurons and astrocytes in vitro. Here, we showed that primary NHA cells co-express low levels of mesenchymal markers Fibronectin and Collagen-1 in culture. These cells transitioned into mesenchymal-like cells when cultured in adherent conditions in serum containing media. The mesenchymal-like derivatives of these cells were characterized based on their morphological changes, high expression of Vimentin and extracellular matrix (ECM) proteins, Collagen-1 and Fibronectin, and decline of neural markers. When incubated in osteogenic and adipogenic induction media, the mesenchymal-like cells differentiated into osteoblasts and adipocytes. Furthermore, NHA cells express markers of neural crest cells, SOX-10 and p75. These data support the idea of ectoderm-derived mesenchymal lineages. These findings suggest that a population of primitive fetal brain cells with neural/neural crest/mesenchymal phenotype, resembles the remarkable phenotypic plasticity of neural crest cells, and differentiates into adipocytes and osteocytes under the influence of environmental factors

  1. Neural markers of errors as endophenotypes in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Dara S Manoach

    2013-07-01

    Full Text Available Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a promising approach.

  2. Neural markers of errors as endophenotypes in neuropsychiatric disorders.

    Science.gov (United States)

    Manoach, Dara S; Agam, Yigal

    2013-01-01

    Learning from errors is fundamental to adaptive human behavior. It requires detecting errors, evaluating what went wrong, and adjusting behavior accordingly. These dynamic adjustments are at the heart of behavioral flexibility and accumulating evidence suggests that deficient error processing contributes to maladaptively rigid and repetitive behavior in a range of neuropsychiatric disorders. Neuroimaging and electrophysiological studies reveal highly reliable neural markers of error processing. In this review, we evaluate the evidence that abnormalities in these neural markers can serve as sensitive endophenotypes of neuropsychiatric disorders. We describe the behavioral and neural hallmarks of error processing, their mediation by common genetic polymorphisms, and impairments in schizophrenia, obsessive-compulsive disorder, and autism spectrum disorders. We conclude that neural markers of errors meet several important criteria as endophenotypes including heritability, established neuroanatomical and neurochemical substrates, association with neuropsychiatric disorders, presence in syndromally-unaffected family members, and evidence of genetic mediation. Understanding the mechanisms of error processing deficits in neuropsychiatric disorders may provide novel neural and behavioral targets for treatment and sensitive surrogate markers of treatment response. Treating error processing deficits may improve functional outcome since error signals provide crucial information for flexible adaptation to changing environments. Given the dearth of effective interventions for cognitive deficits in neuropsychiatric disorders, this represents a potentially promising approach.

  3. Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

    Science.gov (United States)

    Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

    2012-01-01

    Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

  4. Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

    Science.gov (United States)

    Mitchell, Jere H

    2017-06-01

    During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

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

    DEFF Research Database (Denmark)

    Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander

    2015-01-01

    -core architectures that are optimized for the WCET instead of the average-case execution time. The resulting time-predictable resources (processors, interconnect, memory arbiter, and memory controller) and tools (compiler, WCET analysis) are designed to ease WCET analysis and to optimize WCET performance. Compared...... domain shows that the WCET can be reduced for computation-intensive tasks when distributing the tasks on several cores and using the network-on-chip for communication. With three cores the WCET is improved by a factor of 1.8 and with 15 cores by a factor of 5.7.The T-CREST project is the result...

  6. Biomechanical competence of six different bone screws for reconstructive surgery in three different transplants: Fibular, iliac crest, scapular and artificial bone.

    Science.gov (United States)

    Pietsch, Arnold P; Raith, Stefan; Ode, Jan-Eric; Teichmann, Jan; Lethaus, Bernd; Möhlhenrich, Stephan C; Hölzle, Frank; Duda, Georg N; Steiner, Timm

    2016-06-01

    The goal of this study was to determine a combination of screw and transplantation type that offers optimal primary stability for reconstructive surgery. Fibular, iliac crest, and scapular transplants were tested along with artificial bone substrate. Six different kinds of bone screws (Medartis(©)) were compared, each type utilized with one of six specimens from human transplants (n = 6). Controlled screw-in-tests were performed and the required torque was protocolled. Subsequently, pull-out-tests were executed to determine the retention forces. The artificial bone substitute material showed significantly higher retention forces than real bone samples. The self-drilling screws achieved the significantly highest retention values in the synthetic bone substitute material. Cancellous screws achieved the highest retention in the fibular transplants, while self-drilling and cancellous screws demonstrated better retention than cortical screws in the iliac crest. In the scapular graft, no significant differences were found between the screw types. In comparison to the human transplant types, the cortical screws showed the significantly highest values in the fibula and the lowest values in the iliac crest. The best retention was found in the combination of cancellous screws with fibular graft (514.8 N + -252.3 N). For the flat bones (i.e., scapular and illiac crest) we recommend the cancellous screws. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  7. Detection of Bundle Branch Block using Adaptive Bacterial Foraging Optimization and Neural Network

    Directory of Open Access Journals (Sweden)

    Padmavthi Kora

    2017-03-01

    Full Text Available The medical practitioners analyze the electrical activity of the human heart so as to predict various ailments by studying the data collected from the Electrocardiogram (ECG. A Bundle Branch Block (BBB is a type of heart disease which occurs when there is an obstruction along the pathway of an electrical impulse. This abnormality makes the heart beat irregular as there is an obstruction in the branches of heart, this results in pulses to travel slower than the usual. Our current study involved is to diagnose this heart problem using Adaptive Bacterial Foraging Optimization (ABFO Algorithm. The Data collected from MIT/BIH arrhythmia BBB database applied to an ABFO Algorithm for obtaining best(important feature from each ECG beat. These features later fed to Levenberg Marquardt Neural Network (LMNN based classifier. The results show the proposed classification using ABFO is better than some recent algorithms reported in the literature.

  8. The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice

    Directory of Open Access Journals (Sweden)

    Laurie L. Baggio

    2017-11-01

    Conclusions: GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.

  9. Evolution of the new vertebrate head by co-option of an ancient chordate skeletal tissue.

    Science.gov (United States)

    Jandzik, David; Garnett, Aaron T; Square, Tyler A; Cattell, Maria V; Yu, Jr-Kai; Medeiros, Daniel M

    2015-02-26

    A defining feature of vertebrates (craniates) is a pronounced head that is supported and protected by a robust cellular endoskeleton. In the first vertebrates, this skeleton probably consisted of collagenous cellular cartilage, which forms the embryonic skeleton of all vertebrates and the adult skeleton of modern jawless and cartilaginous fish. In the head, most cellular cartilage is derived from a migratory cell population called the neural crest, which arises from the edges of the central nervous system. Because collagenous cellular cartilage and neural crest cells have not been described in invertebrates, the appearance of cellular cartilage derived from neural crest cells is considered a turning point in vertebrate evolution. Here we show that a tissue with many of the defining features of vertebrate cellular cartilage transiently forms in the larvae of the invertebrate chordate Branchiostoma floridae (Florida amphioxus). We also present evidence that during evolution, a key regulator of vertebrate cartilage development, SoxE, gained new cis-regulatory sequences that subsequently directed its novel expression in neural crest cells. Together, these results suggest that the origin of the vertebrate head skeleton did not depend on the evolution of a new skeletal tissue, as is commonly thought, but on the spread of this tissue throughout the head. We further propose that the evolution of cis-regulatory elements near an ancient regulator of cartilage differentiation was a major factor in the evolution of the vertebrate head skeleton.

  10. Breeding Double-crested Cormorants and Wading Birds on Isla Alcatraz, Sonora, México

    Science.gov (United States)

    Jennifer N. Duberstein; Virginia Jimenez-Serrania; Tad A. Pfister; Kirsten E. Lindquist; Lorayne Meltzer

    2005-01-01

    Isla Alcatraz is a small volcanic island in the Eastern Midriff Island region of the Gulf of California, approximately 1.4 km from the fishing community of Bahía de Kino, Sonora, México. The island falls under the protection of the Gulf Island Reserve system for wildlife and migratory birds. Isla Alcatraz is home to one of the largest Double-crested Cormorant (

  11. A framework for automatic heart sound analysis without segmentation

    Directory of Open Access Journals (Sweden)

    Tungpimolrut Kanokvate

    2011-02-01

    Full Text Available Abstract Background A new framework for heart sound analysis is proposed. One of the most difficult processes in heart sound analysis is segmentation, due to interference form murmurs. Method Equal number of cardiac cycles were extracted from heart sounds with different heart rates using information from envelopes of autocorrelation functions without the need to label individual fundamental heart sounds (FHS. The complete method consists of envelope detection, calculation of cardiac cycle lengths using auto-correlation of envelope signals, features extraction using discrete wavelet transform, principal component analysis, and classification using neural network bagging predictors. Result The proposed method was tested on a set of heart sounds obtained from several on-line databases and recorded with an electronic stethoscope. Geometric mean was used as performance index. Average classification performance using ten-fold cross-validation was 0.92 for noise free case, 0.90 under white noise with 10 dB signal-to-noise ratio (SNR, and 0.90 under impulse noise up to 0.3 s duration. Conclusion The proposed method showed promising results and high noise robustness to a wide range of heart sounds. However, more tests are needed to address any bias that may have been introduced by different sources of heart sounds in the current training set, and to concretely validate the method. Further work include building a new training set recorded from actual patients, then further evaluate the method based on this new training set.

  12. Recent population size, trends, and limiting factors for the double-crested Cormorant in Western North America

    Science.gov (United States)

    Adkins, Jessica Y.; Roby, Daniel D.; Lyons, Donald E.; Courtot, Karen N.; Collis, Ken; Carter, Harry R.; Shuford, W. David; Capitolo, Phillip J.

    2014-01-01

    The status of the double-crested cormorant (Phalacrocorax auritus) in western North America was last evaluated during 1987–2003. In the interim, concern has grown over the potential impact of predation by double-crested cormorants on juvenile salmonids (Oncorhynchusspp.), particularly in the Columbia Basin and along the Pacific coast where some salmonids are listed for protection under the United States Endangered Species Act. Recent re-evaluations of double-crested cormorant management at the local, flyway, and federal level warrant further examination of the current population size and trends in western North America. We collected colony size data for the western population (British Columbia, Washington, Oregon, Idaho, California, Nevada, Utah, Arizona, and the portions of Montana, Wyoming, Colorado and New Mexico west of the Continental Divide) by conducting aircraft-, boat-, or ground-based surveys and by cooperating with government agencies, universities, and non-profit organizations. In 2009, we estimated approximately 31,200 breeding pairs in the western population. We estimated that cormorant numbers in the Pacific Region (British Columbia, Washington, Oregon, and California) increased 72% from 1987–1992 to circa 2009. Based on the best available data for this period, the average annual growth rate (λ) of the number of breeding birds in the Pacific Region was 1.03, versus 1.07 for the population east of the Continental Divide during recent decades. Most of the increase in the Pacific Region can be attributed to an increase in the size of the nesting colony on East Sand Island in the Columbia River estuary, which accounts for about 39% of all breeding pairs in the western population and is the largest known breeding colony for the species (12,087 breeding pairs estimated in 2009). In contrast, numbers of breeding pairs estimated in coastal British Columbia and Washington have declined by approximately 66% during this same period. Disturbance at breeding

  13. Discharge Coefficient of Rectangular Short-Crested Weir with Varying Slope Coefficients

    Directory of Open Access Journals (Sweden)

    Yuejun Chen

    2018-02-01

    Full Text Available Rectangular short-crested weirs are widely used for simple structure and high discharge capacity. As one of the most important and influential factors of discharge capacity, side slope can improve the hydraulic characteristics of weirs at special conditions. In order to systemically study the effects of upstream and downstream slope coefficients S1 and S2 on overflow discharge coefficient in a rectangular short-crested weir the Volume of Fluid (VOF method and the Renormalization Group (RNG κ-ε turbulence model are used. In this study, the slope coefficient ranges from V to 3H:1V and each model corresponds to five total energy heads of H0 ranging from 8.0 to 24.0 cm. Comparisons of discharge coefficients and free surface profiles between simulated and laboratory results display a good agreement. The simulated results show that the difference of discharge coefficients will decrease with upstream slopes and increase with downstream slopes as H0 increases. For a given H0, the discharge coefficient has a convex parabolic relation with S1 and a piecewise linearity relation with S2. The maximum discharge coefficient is always obtained at S2 = 0.8. There exists a difference between upstream and downstream slope coefficients in the influence range of free surface curvatures. Furthermore, a proposed discharge coefficient equation by nonlinear regression is a function of upstream and downstream slope coefficients.

  14. Development and degeneration of dorsal root ganglia in the absence of the HMG-domain transcription factor Sox10

    DEFF Research Database (Denmark)

    Sonnenberg-Riethmacher, Eva; Miehe, Michaela; Stolt, Claus C.

    2001-01-01

    neurogenesis seemed initially normal. A degeneration of motoneurons and sensory neurons occurred later in development. The mechanism that leads to the dramatic effects on the neural crest derived cell lineages in the dorsal root ganglia (DRG), however, has not been examined up to now. Here, we provide...... a detailed analysis of proliferation and apoptosis in the DRG during the time of their generation and lineage segregation (between E 9.5 and E 11.5). We show that both increased apoptosis as well as decreased proliferation of neural crest cells contribute to the observed hypomorphism....

  15. Theoretical Investigation of Peak-Delay Force Reduction for Caissons Exposed to Non-breaking Short-Crested Waves

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Liu, Z.

    In nature coastal structures are exposed to oblique short-crested waves. The effect of wave incident angle on total wave force on a long caisson are twofold. The one is the force reduction due to the reduction of instantaneous point pressure on the caisson, named point-pressure force reduction....... The other is the force reduction due to the fact that the peak pressures do not occur simultaneously along the caisson, named peak-delay force reduction. These two reduction effects can also be expected with short-crested waves, as the short-crestedness of waves means the spreading of wave energy over...... a range of incident angles. The peak-delay force reduction, i.e. no simultaneous peak along caisson, is of particular interest because the equipment improvement in construction enables the building of considerably long caissons. In Japan length of caissons exceeds often 100m. This paper will concentrate...

  16. Heart Development, Diseases, and Regeneration - New Approaches From Innervation, Fibroblasts, and Reprogramming.

    Science.gov (United States)

    Ieda, Masaki

    2016-09-23

    It is well known that cardiac function is tightly controlled by neural activity; however, the molecular mechanism of cardiac innervation during development and the relationship with heart disease remain undetermined. My work has revealed the molecular networks that govern cardiac innervation and its critical roles in heart diseases such as silent myocardial ischemia and arrhythmias. Cardiomyocytes proliferate during embryonic development, but lose their proliferative capacity after birth. Cardiac fibroblasts are a major source of cells during fibrosis and induce cardiac hypertrophy after myocardial injury in the adult heart. Despite the importance of fibroblasts in the adult heart, the role of fibroblasts in embryonic heart development was previously not determined. I demonstrated that cardiac fibroblasts play important roles in myocardial growth and cardiomyocyte proliferation during embryonic development, and I identified key paracrine factors and signaling pathways. In contrast to embryonic cardiomyocytes, adult cardiomyocytes have little regenerative capacity, leading to heart failure and high mortality rates after myocardial infarction. Leveraging the knowledge of developmental biology, I identified cardiac reprogramming factors that can directly convert resident cardiac fibroblasts into cardiomyocytes for heart regeneration. These findings greatly improved our understanding of heart development and diseases, and provide a new strategy for heart regenerative therapy. (Circ J 2016; 80: 2081-2088).

  17. 76 FR 15971 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-03-22

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

  18. 76 FR 22699 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Teleconference

    Science.gov (United States)

    2011-04-22

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

  19. Neural Tube Defect in Alive Neonates: Incidence Rate and Predisposing Factors

    Directory of Open Access Journals (Sweden)

    F Haghollahi

    2008-06-01

    Full Text Available Background: Neural Tube Defect (NTD characterized by failure of neural tube to close properly be the second most common born defect after congenital heart disease. The most prevalent forms of NTD are Anencephaly and Spinal-bifida. Many factors are involved in this anomaly. New researches suggest environmental factors like radiation, hyperthermia, Vitamin A and acid folic deficiency, anti epileptic drug like Carbamazepine, Phenobarbital, phenytoin, Folic acid antagonist like Sulfasalazine, Triametherine and systemic disease like diabet mellitus, obesity, genetic factors, the most schance 40 to 70 percentages.Methods: In this survey cross sectional study was conducted in five hospitals depend to Tehran university during three years. Study subject identified through review of admission and discharge at major hospital through regular contact with newborn nurseries and birth hospital.Results: In 38473 reported cases, 143 cases have neural tube defect. Among NTD cases, 11.9% of mothers had medical diseases in their previous history such as diabetes mellitus, epilepsy-psychiatric, and disorder-heart diseases. In this study group, 5.6% have preclampsia during pregnancy period. The most common NTD anomaly in this study was anencephaly and meningomyelocele that was different from studies in literature.Conclusion: NTD result from failure of neural tube close threats fetus health up to 28 days after conception. When is often prior to the recognition of pregnancy since many pregnancy are unplanned NTD prevention is best achieve by adequate daily folic acid intake thought of reproductive ages .educational effort to promote daily intake of folic acid supplemental by women of reproductive age and NTD risk factor should be done. Early diagnostic procedure for high risk pregnancy advised.

  20. 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.

  1. Genomic signatures of near-extinction and rebirth of the crested ibis and other endangered bird species

    DEFF Research Database (Denmark)

    Li, Shengbin; Li, Bo; Cheng, Cheng

    2014-01-01

    sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures...

  2. 78 FR 25263 - Eagle Mountain Pumped Storage Hydroelectric Project; Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-04-30

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

  3. 77 FR 43280 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2012-07-24

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

  4. Origin of heart rate variability and turbulence: an appraisal of autonomic modulation of cardiovascular function.

    Directory of Open Access Journals (Sweden)

    Federico eLombardi

    2011-12-01

    Full Text Available Assessment of autonomic modulation of sinus node by non-invasive techniques has provided relevant clinical information in patients with several cardiac and non-cardiac diseases and has facilitated the appraisal of neural regulatory mechanisms in normal and diseased subjects. The finding that even during resting conditions the heart period changes on a beat to beat basis and that after a premature ventricular beat there are small variations in RR interval whose measurements may be utilised to evaluate the autonomic modulation of sinus node, has provided unprecedented clinical and pathophysiological information. Heart rate variability (HRV and Heart Rate Turbulence (HRT have been extensively utilised in the clinical setting. To explain the negative predictive value of a reduced HRV it was determined that overall HRV was largely dependent on vagal mechanisms and that a reduction in HRV could reflect an increased sympathetic and a reduced vagal modulation of sinus node; i.e. an autonomic alteration favouring cardiac electrical instability. This initial interpretation was challenged by several findings indicating a greater complexity of the relationship between neural input and sinus node responsiveness as well as the possible interference with non-neural mechanisms.Under controlled conditions, however, the computation of low and high frequency components and of their ratio seems capable of providing adequate information on sympatho-vagal balance in normal subjects as well as in most patients with a preserved left ventricular function, thus providing a unique tool to investigate neural control mechanisms. Analysis on non-linear dynamics of HRV has also been utilised to describe the fractal like characteristic of the variability signal and proven effective to identify patients at risk for sudden cardiac death. A reduction on HRT parameters reflecting reduced baroreflex sensitivity as a likely result of a reduced vagal and of an increased sympathetic

  5. A healthy heart is not a metronome: An integrative review of the heart’s anatomy and heart rate variability

    Directory of Open Access Journals (Sweden)

    Fredric Bruce Shaffer

    2014-09-01

    Full Text Available Heart rate variability (HRV, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF, very-low-frequency (VLF, low-frequency (LF, and high-frequency (HF bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges’ polyvagal theory, Thayer and colleagues’ neurovisceral integration model, Lehrer, Vaschillo, and Vaschillo’s resonance frequency model, and the Institute of HeartMath’s coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.

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

    Czech Academy of Sciences Publication Activity Database

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

    2007-01-01

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

  7. 78 FR 26358 - Eagle Mountain Pumped Storage Hydroelectric Project, Eagle Crest Energy; Notice of Meeting With...

    Science.gov (United States)

    2013-05-06

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

  8. How insights from cardiovascular developmental biology have impacted the care of infants and children with congenital heart disease

    Science.gov (United States)

    Chin, Alvin J.; Saint-Jeannet, Jean-Pierre; Lo, Cecilia W.

    2012-01-01

    To illustrate the impact developmental biology and genetics have already had on the clinical management of the million infants born worldwide each year with CHD, we have chosen three stories which have had particular relevance for pediatric cardiologists, cardiothoracic surgeons, cardiac anesthesiologists, and cardiac nurses. First, we show how Margaret Kirby’s finding of the unexpected contribution of an ectodermal cell population – the cranial neural crest – to the aortic arch arteries and arterial pole of the embryonic avian heart provided a key impetus to the field of cardiovascular patterning. Recognition that a majority of patients affected by the neurocristopathy DiGeorge syndrome have a chromosome 22q11 deletion, have also spurred tremendous efforts to characterize the molecular mechanisms contributing to this pathology, assigning a major role to the transcription factor Tbx1. Second, synthesizing the work of the last two decades by many laboratories on a wide gamut of metazoans (invertebrates, tunicates, agnathans, teleosts, lungfish, amphibians, and amniotes), we review the >20 major modifications and additions to the ancient circulatory arrangement composed solely of a unicameral (one-chambered), contractile myocardial tube and a short proximal aorta. Two changes will be discussed in detail – the interposition of a second cardiac chamber in the circulation and the septation of the cardiac ventricle. By comparing the developmental genetic data of several model organisms, we can better understand the origin of the various components of the multicameral (multi-chambered) heart seen in humans. Third, Martina Brueckner’s discovery that a faulty axonemal dynein was responsible for the phenotype of the iv/iv mouse (the first mammalian model of human heterotaxy) focused attention on the biology of cilia. We discuss how even the care of the complex cardiac and non-cardiac anomalies seen in heterotaxy syndrome, which have long seemed impervious to

  9. History, heresy and radiology in scientific discovery.

    Science.gov (United States)

    McCredie, J

    2009-10-01

    Nowadays, most drugs reach the market after research has established their pharmacology, safety and efficacy. That was not always the case 50 years ago. Thalidomide was used before its target cell or mode of action were known. Commencing with the thalidomide catastrophe--an epidemic of gross birth defects (1958-1962)--thalidomide's origins are revisited to show how this drug came to be made and sold in the 1950s. Thalidomide intersected with Australian radiology in the 1970s. The site and mode of action of the drug was deduced from X-rays of thalidomide-induced bone defects, which have classical radiological signs of sensory neuropathic osteoarthropathy. The longitudinal reduction deformities follow the distribution of segmental sensory innervation of the limb skeleton, indicating neural crest as the target organ. Injury to one level of neural crest halts normal neurotrophism and deletes the dependent segment--a previously unrecognised embryonic mechanism that explains most non-genetic birth defects. The final common pathway is neural crest injury and failure of normal neurotrophism to result in longitudinal reduction deformities, for example, phocomelia.

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

    Science.gov (United States)

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

    2016-06-01

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

  11. Reproductive behavior of the Red-crested Finch Coryphospingus cucullatus (Aves: Thraupidae in southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Paulo V.Q. Zima

    Full Text Available ABSTRACT Several behavioral aspects of the Red-crested Finch Coryphospingus cucullatus (Statius Müller, 1776 are poorly studied. Here we provide reproductive information on 16 active nests. This information may be valuable to elucidate the phylogenetic relationships of this bird, and to design plans to manage it. Nesting activities occurred from October to February. Clutches consisted of two to three eggs (2.06 ± 0.25, which were laid on consecutive days. Incubation usually started the morning the females laid their last egg and lasted 11.27 ± 0.47 days. Hatching was synchronous, or happened at a one-day interval. The nestling stage lasted 12 ± 0.89 days. Only females incubated the eggs and they fed the young more often than the males did. Overall nesting success, from incubation to fledging, was 28.2%. Nest architecture and egg color proved to be diagnostic characteristics of Coryphospingus , supporting its maintenance as a distinct genus within the recently proposed sub-family Tachyphoninae. Red-crested Finches showed a preference for certain nesting sites, i.e., forest borders or a Cerrado in late regeneration stage. This information can be useful to programs aiming to release illegally trapped individuals.

  12. Static Histomorphometry of the iliac crest after 360 days of antiorthostatic bed rest with and without countermeasures

    Science.gov (United States)

    Thomsen, J. S.; Morukov, B. V.; Vico, L.; Saparin, P. I.; Gowin, W.

    The loss of bone during immobilization is well-known and investigated, whereas the structural changes human cancellous bone undergoes during disuse is less well examined. The aim of the study was to examine the influence of hypokinesia on the static histomorphometric measures of the iliac crest using a 360-day-long bed rest experiment, simulating exposure to microgravity. Eight healthy males underwent 360 days of 5° head-down tilt bed rest. Three subjects were treated with the bisphosphonate Xidifon (900 mg/day) combined with a treadmill and ergonometer exercise regimen (1--2 hours/day) for the entire study period. Five subjects underwent 120 days of bed rest without countermeasures followed by 240 days of bed rest with the treadmill and ergonometer exercise regimen. Transiliac bone biopsies were obtained either at day 0 and 360 or at day 0, 120, and 360 at alternating sides of the ileum. The biopsies were embedded in methylmethacrylate, cut in 7-μm-thick sections, stained with Goldner trichrome, and static histomorphometry was performed. 120 days of bed rest without countermeasures resulted in decreased trabecular bone volume (-6.3%, p = 0.046) and trabecular number (-10.2%, p = 0.080) and increased trabecular separation (14.7%, p = 0.020), whereas 240 days of subsequent bed rest with exercise treatment prevented further significant deterioration of the histomorphometric measures. 360 days of bed rest with bisphosphonate and exercise treatment did not induce any significant changes in any of the histomorphometric measures. The study showed that 120 days of antiorthostatic bed rest without countermeasures induced significant deterioration of iliac crest trabecular bone histomorphometric properties. There are indications that the immobilization induced changes involve a loss of trabeculae rather than a general thinning of the trabeculae. On average, the countermeasures consisting of either bisphosphonate and exercise or exercise alone were able to either prevent

  13. 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.

  14. OP-1 compared with iliac crest autograft in instrumented posterolateral fusion a randomized, multicenter non-inferiority trial

    NARCIS (Netherlands)

    Delawi, Diyar; Jacobs, Wilco; Van Susante, Job L C; Rillardon, Ludovic; Prestamburgo, Domenico; Specchia, Nicola; Gay, Emmanuel; Verschoor, Nico; Garcia-Fernandez, Carlos; Guerado, Enrique; Van Ufford, Henriette Quarles; Kruyt, Moyo C.; Dhert, Wouter J A; Cumhur Oner, F.

    2016-01-01

    Background: Spinal fusion with the use of autograft is a commonly performed procedure. However, harvesting of bone from the iliac crest is associated with complications. Bone morphogenetic proteins (BMPs) are extensively used as alternatives, often without sufficient evidence of safety and efficacy.

  15. Development and characterization of polymorphic microsatellitemarkers for the crested caracara, Caracara cheriway

    Science.gov (United States)

    Vaughn, Erin E.; Dwyer, James F.; Morrison, Joan L.; Culver, Melanie

    2015-01-01

    We isolated novel microsatellites from the crested caracara (Caracara cheriway) with a shotgun pyrosequencing approach. We tested 80 loci for polymorphism among 20 individuals from the threatened Florida population. Fourteen loci were polymorphic. The mean number of alleles was 2.21 (range 2–3) and the mean observed heterozygosity was 0.41 (range 0.15–0.65). None of the 14 polymorphic loci exhibited significant linkage disequilibrium nor did they deviate significantly from Hardy–Weinberg expectations. We also report 16 monomorphic loci.

  16. Bidirectional Cardio-Respiratory Interactions in Heart Failure

    Directory of Open Access Journals (Sweden)

    Nikola N. Radovanović

    2018-03-01

    Full Text Available We investigated cardio-respiratory coupling in patients with heart failure by quantification of bidirectional interactions between cardiac (RR intervals and respiratory signals with complementary measures of time series analysis. Heart failure patients were divided into three groups of twenty, age and gender matched, subjects: with sinus rhythm (HF-Sin, with sinus rhythm and ventricular extrasystoles (HF-VES, and with permanent atrial fibrillation (HF-AF. We included patients with indication for implantation of implantable cardioverter defibrillator or cardiac resynchronization therapy device. ECG and respiratory signals were simultaneously acquired during 20 min in supine position at spontaneous breathing frequency in 20 healthy control subjects and in patients before device implantation. We used coherence, Granger causality and cross-sample entropy analysis as complementary measures of bidirectional interactions between RR intervals and respiratory rhythm. In heart failure patients with arrhythmias (HF-VES and HF-AF there is no coherence between signals (p < 0.01, while in HF-Sin it is reduced (p < 0.05, compared with control subjects. In all heart failure groups causality between signals is diminished, but with significantly stronger causality of RR signal in respiratory signal in HF-VES. Cross-sample entropy analysis revealed the strongest synchrony between respiratory and RR signal in HF-VES group. Beside respiratory sinus arrhythmia there is another type of cardio-respiratory interaction based on the synchrony between cardiac and respiratory rhythm. Both of them are altered in heart failure patients. Respiratory sinus arrhythmia is reduced in HF-Sin patients and vanished in heart failure patients with arrhythmias. Contrary, in HF-Sin and HF-VES groups, synchrony increased, probably as consequence of some dominant neural compensatory mechanisms. The coupling of cardiac and respiratory rhythm in heart failure patients varies depending on the

  17. Maternal obesity and congenital heart defects: a population-based study123

    Science.gov (United States)

    Mills, James L; Troendle, James; Conley, Mary R; Carter, Tonia; Druschel, Charlotte M

    2010-01-01

    Background: Obesity affects almost one-third of pregnant women and causes many complications, including neural tube defects. It is not clear whether the risk of congenital heart defects, the most common malformations, is also increased. Objective: This study was conducted to determine whether obesity is associated with an increased risk of congenital heart defects. Design: A population-based, nested, case-control study was conducted in infants born with congenital heart defects and unaffected controls from the cohort of all births (n = 1,536,828) between 1993 and 2003 in New York State, excluding New York City. The type of congenital heart defect, maternal body mass index (BMI; in kg/m2), and other risk factors were obtained from the Congenital Malformations Registry and vital records. Mothers of 7392 congenital heart defect cases and 56,304 unaffected controls were studied. Results: All obese women (BMI ≥ 30) were significantly more likely than normal-weight women (BMI: 19–24.9) to have children with a congenital heart defect [odds ratio (OR): 1.15; 95% CI: 1.07, 1.23; P heart defects with increasing maternal obesity (P heart syndrome, aortic stenosis, pulmonic stenosis, and tetralogy of Fallot. Conclusions: Obese, but not overweight, women are at significantly increased risk of bearing children with a range of congenital heart defects, and the risk increases with increasing BMI. Weight reduction as a way to reduce risk should be investigated. PMID:20375192

  18. CREST: Center for Renewable Energy Science and Technology

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-20

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

  19. Bidirectional Cardio-Respiratory Interactions in Heart Failure.

    Science.gov (United States)

    Radovanović, Nikola N; Pavlović, Siniša U; Milašinović, Goran; Kirćanski, Bratislav; Platiša, Mirjana M

    2018-01-01

    We investigated cardio-respiratory coupling in patients with heart failure by quantification of bidirectional interactions between cardiac (RR intervals) and respiratory signals with complementary measures of time series analysis. Heart failure patients were divided into three groups of twenty, age and gender matched, subjects: with sinus rhythm (HF-Sin), with sinus rhythm and ventricular extrasystoles (HF-VES), and with permanent atrial fibrillation (HF-AF). We included patients with indication for implantation of implantable cardioverter defibrillator or cardiac resynchronization therapy device. ECG and respiratory signals were simultaneously acquired during 20 min in supine position at spontaneous breathing frequency in 20 healthy control subjects and in patients before device implantation. We used coherence, Granger causality and cross-sample entropy analysis as complementary measures of bidirectional interactions between RR intervals and respiratory rhythm. In heart failure patients with arrhythmias (HF-VES and HF-AF) there is no coherence between signals ( p respiratory signal in HF-VES. Cross-sample entropy analysis revealed the strongest synchrony between respiratory and RR signal in HF-VES group. Beside respiratory sinus arrhythmia there is another type of cardio-respiratory interaction based on the synchrony between cardiac and respiratory rhythm. Both of them are altered in heart failure patients. Respiratory sinus arrhythmia is reduced in HF-Sin patients and vanished in heart failure patients with arrhythmias. Contrary, in HF-Sin and HF-VES groups, synchrony increased, probably as consequence of some dominant neural compensatory mechanisms. The coupling of cardiac and respiratory rhythm in heart failure patients varies depending on the presence of atrial/ventricular arrhythmias and it could be revealed by complementary methods of time series analysis.

  20. Can footwall unloading explain late Cenozoic uplift of the Sierra Nevada crest?

    Science.gov (United States)

    Thompson, G.A.; Parsons, T.

    2009-01-01

    Globally, normal-fault displacement bends and warps rift flanks upwards, as adjoining basins drop downwards. Perhaps the most evident manifestations are the flanks of the East African Rift, which cuts across the otherwise minimally deformed continent. Flank uplift was explained by Vening Meinesz (1950, Institut Royal Colonial Belge, Bulletin des Seances, v. 21, p. 539-552), who recognized that isostasy should cause uplift of a normal-faulted footwall and subsidence of its hanging wall. Uplift occurs because slip on a dipping normal fault creates a broader root of less-dense material beneath the footwall, and a narrowed one beneath the hanging wall. In this paper, we investigate the potential influence of this process on the latest stages of Sierra Nevada uplift. Through theoretical calculations and 3D finite element modelling, we find that cumulative slip of about 4km on range-front faults would have produced about 1.3km peak isostatic uplift at the ridge crest. Numerical models suggest that the zone of uplift is narrow, with the width controlled by bending resistance of the seismogenic crust. We conclude that footwall unloading cannot account for the entire elevation of the Sierran crest above sea level, but if range-front faulting initiated in an already elevated plateau like the adjacent Basin and Range Province, then a hybrid model of pre-existing regional uplift and localized footwall unloading can account for the older and newer uplift phases suggested by the geologic record.

  1. Computerized determination of 3-D connectivity density in human iliac crest bone biopsies

    DEFF Research Database (Denmark)

    Thomsen, J.S.; Mosekilde, Li.; Barlach, J.

    1996-01-01

    Combining the physical disector principle with an algorithm for automatic non-linear alignment of disector pairs we have developed a software system for direct measurement of 3D connectivity densities in iliac crest bone biopsies. The method was applied to biopsies from 14 non-selected autopsy...... cases: 7 men (age range 20-84 yr) and 7 women (age range 20-86 yr). The study reveals decreases in both trabecular bone mass and connectivity density with age in women....

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

    NARCIS (Netherlands)

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

    OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND

  3. The Neural Baroreflex Pathway in Subjects With Metabolic Syndrome

    OpenAIRE

    Zanoli, Luca; Empana, Jean-Philippe; Estrugo, Nicolas; Escriou, Guillaume; Ketthab, Hakim; Pruny, Jean-Francois; Castellino, Pietro; Laude, Dominique; Thomas, Frederique; Pannier, Bruno; Jouven, Xavier; Boutouyrie, Pierre; Laurent, Stephane

    2016-01-01

    Abstract The mechanisms that link metabolic syndrome (MetS) to increased cardiovascular risk are incompletely understood. We examined whether MetS is associated with the neural baroreflex pathway (NBP) and whether any such associations are independent of blood pressure values. This study involved the cross-sectional analysis of data on 2835 subjects aged 50 to 75 years from the Paris Prospective Study 3. The prevalence of MetS was defined according to the American Heart Association/National H...

  4. Diet of double-crested cormorants wintering in Texas

    Science.gov (United States)

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

    1993-01-01

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

  5. Assessment of GPS Multifrequency Signal Characteristics During Periods of Ionospheric Scintillations from an Anomaly Crest Location

    Science.gov (United States)

    Goswami, S.; Paul, K. S.; Paul, A.

    2017-09-01

    Multifrequency GPS transmissions have provided the opportunity for testing the applicability of the principle of frequency diversity for scintillation mitigation. Published results addressing this issue with quantified estimates are not available in literature, at least from the anomaly crest location of the Indian longitude sector. Multifrequency scattering within the same L band is often the attributed cause behind simultaneous decorrelated signal fluctuations. The present paper aims to provide proportion of time during scintillation patches that decorrelations are found across GPS L1, L2, and L5 frequencies associated with high S4, corresponding high values of scattering coefficients, and large receiver position deviations thereby seriously compromising the performance of satellite-based navigation system. Results from the anomaly crest station at Calcutta indicate maximum 40% of scintillation time during February-April 2014 and 33% during August-October 2014 that the signals are decorrelated. It is important to note that it is only during these time intervals that the principle of frequency diversity could be applied for scintillation mitigation.

  6. 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...

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

    Science.gov (United States)

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

    2017-04-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    instabilities. These correctly lead to well-known (nearly symmetric) recurrence cycles below a previously established breaking threshold steepness, and to an asymmetric evolution (characterized by a permanent transfer of energy to the lower side-band) above this threshold, with dissipation from a smoothing...... that the unstable evolution of these initially three-dimensional waves leads to an asymmetric evolution, even for weakly nonlinear cases presumably well below breaking. This is characterized by an energy transfer to the lower side-band, which is also accompanied by a similar transfer to more distant upper side......-bands. At larger steepness, the evolution leads to a permanent downshift of both the mean and peak frequencies, driven in part by dissipation, effectively breaking the quasi-recurrence cycle. A single case involving a class Ib short-crested wave instability at relatively large steepness is also considered, which...

  9. The status of whitebark pine along the Pacific Crest National Scenic Trail on the Umpqua National Forest.

    Science.gov (United States)

    Ellen Michaels Goheen; Donald J. Goheen; Katy Marshall; Robert S. Danchok; John A. Petrick; Diane E. White

    2002-01-01

    Because of concern over widespread population declines, the distribution, stand conditions, and health of whitebark pine (Pinus albicaulis Englem.) were evaluated along the Pacific Crest National Scenic Trail on the Umpqua National Forest. Whitebark pine occurred on 76 percent of the survey transects. In general, whitebark pine was found in stands...

  10. Local time, seasonal, and solar cycle dependency of longitudinal variations of TEC along the crest of EIA over India

    Science.gov (United States)

    Sunda, Surendra; Vyas, B. M.

    2013-10-01

    global wave number 4 structure in the Indian longitudinal region spanning from ~70 to 95°E forming the upward slope of the peak in the total electron content (TEC) are reported along the crest of equatorial ionization anomaly (EIA). The continuous and simultaneous measurements from five GPS stations of GPS Aided Geo Augmented Navigation (GAGAN) network are used in this study. The long-term database (2004-2012) is utilized for examining the local time, seasonal, and solar cycle dependency on the longitudinal variations of TEC. Our results confirm the existence of longitudinal variations of TEC in accordance with wave number 4 longitudinal structure including its strength. The results suggest that these variations, in general, start to develop at ~09 LT, achieve maximum strength at 12-15 LT, and decay thereafter, the decay rate depending on the season. They are more pronounced in equinoctial season followed by summer and winter. The longitudinal variations persist beyond midnight in equinox seasons, whereas in winter, they are conspicuously absent. Interestingly, they also exhibit significant solar cycle dependence in the solstices, whereas in the equinoxes, they are independent of solar activity. The comparison of crest-to-trough ratio (CTR) in the eastern (92°E) and western (72°E) extreme longitudes reveals higher CTR on the eastern side than over the western extreme, suggesting the role of nonmigrating tides in modulating the ExB vertical drift and the consequential EIA crest formation.

  11. An autoradiographic analysis of the development of the chick trigeminal ganglion

    International Nuclear Information System (INIS)

    Amico-Martel, A.D; Noden, D.M.

    1980-01-01

    The avian trigeminal ganglion, which is embryonically derived from the neural crest and epidermal placodes, consists of two topographically segregated classes of immature neurons, large and small, during the second week of incubation, and two neuronal cell types, dark and light, interspersed throughout the mature ganglion. In order to establish the times of terminal mitosis of trigeminal sensory neurons, embryos were treated with [ 3 H]thymidine during the first week of incubation and their ganglia fixed on embryonic day 11. The embryonically large, distal, placodal-derived neurons were generated between days 2 and 5, while the small, proximal, neural crest-derived neurons were formed mostly between days 4 and 7. By comparing the locations of labelled cells in ganglia treated with isotope but fixed on day 18 on incubation with their 11-day counterparts, it was shown that there are no morpho-genetic rearrangements of neurons during the final week of incubation. Thus, no unique relationship exists between the two neuron types in the mature ganglion and the two cell classes in the immature trigeminal. Therefore, both the light and the dark neurons in the mature trigeminal ganglion arise from neural crest as well as placodal primordia. (author)

  12. Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

    Science.gov (United States)

    Lal, Brajesh K; Beach, Kirk W; Roubin, Gary S; Lutsep, Helmi L; Moore, Wesley S; Malas, Mahmoud B; Chiu, David; Gonzales, Nicole R; Burke, J Lee; Rinaldi, Michael; Elmore, James R; Weaver, Fred A; Narins, Craig R; Foster, Malcolm; Hodgson, Kim J; Shepard, Alexander D; Meschia, James F; Bergelin, Robert O; Voeks, Jenifer H; Howard, George; Brott, Thomas G

    2012-09-01

    In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31

  13. Structural peculiarities of the sedimentary cover of the MAR crest depressions (5°-8°N) in the Equatorial Atlantics

    Science.gov (United States)

    Skolotnev, S. G.; Tsukanov, N. V.; Turko, N. N.; Peyve, A. A.

    2003-04-01

    The analysis of the bottom relief structure investigated with multibeam SIMRAD 12S and sedimentary cover of depressions investigeted with PARASAUND in the MAR crest zone near Sierra-Leone Fault (22 Cruise of the RV "Akademik Nikolay Strachov", and 10 Cruise of the RV "Akademik Ioffe") point on the complicated character of the tectonic activity distribution in this region. The left-lateral displacements of the rift velley and the absence of transform faults are typical for this region. Two extremely deep rift depressions (up to 5000 m) are located in the rift valley: one on 5°54'N latitude (Markov depression) and the other on 5°46'N latitude. About 40 m sediments cover their bottom. On contary, in the depression located parallel to the rift valley directly to the west from the two mentioned rift depressions the sedimentary cover is absent and bottom has very dissected, apparently volcanic, relief. In the MAR crest zone in 20 miles to the south-west from the Markov and 5°46'N depressions one can see a system of depressions oriented both parallel and oblique to the rift valley. There are filled by the sediments of different thickness. The sedimentary cover of these depressions often is tired and deformed by diapir and horst uplifts. Dredging data show, that basalts, which represent, according to their petro-geo-chemical characteristics the enriched MORB basalts and alkaline basalts compose these uplifts. Irregular distribution and character of composition of the sediments in the depressions of crest zone of the MAR segment under consideration along with high volcanic activity outside the axial spreding zone show that tectonic and volcanic activity in this area are distributed all over the crest zone. The complicated character of this activity is obviosly caused by two reasons. From one hand it may be a deep mantle plum, as inferred from basalt composition and from the other hand it may be the lithosphere blocks displacements along the left-lateral strike slips.

  14. 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

  15. Epigenetic control of skull morphogenesis by histone deacetylase 8

    Science.gov (United States)

    Haberland, Michael; Mokalled, Mayssa H.; Montgomery, Rusty L.; Olson, Eric N.

    2009-01-01

    Histone deacetylases (Hdacs) are transcriptional repressors with crucial roles in mammalian development. Here we provide evidence that Hdac8 specifically controls patterning of the skull by repressing a subset of transcription factors in cranial neural crest cells. Global deletion of Hdac8 in mice leads to perinatal lethality due to skull instability, and this is phenocopied by conditional deletion of Hdac8 in cranial neural crest cells. Hdac8 specifically represses the aberrant expression of homeobox transcription factors such as Otx2 and Lhx1. These findings reveal how the identity and patterning of vertebrate-specific portions of the skull are epigenetically controlled by a histone deacetylase. PMID:19605684

  16. Diagnosis and treatment of a carcinoid tumor using iodine-131 meta-iodobenzylguanidine

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.; Den Hartog Jager, F.C.; Van Gennip, A.H.; Marcuse, H.R.; Taal, B.G.

    1986-01-01

    Scintigraphy using I-131 meta-iodobenzylguanidine has been introduced as an effective method to detect pheochromocytomas and neuroblastomas, and the radiopharmaceutical also is applied in therapy of these tumors. The authors present a case of a metastatic gastric carcinoid tumor, another neural crest tumor, concentrating I-131 MIBG, which was documented by conventional scintigraphy and SPECT in correlation with CT scans and colloid scintigrams of the liver. Two therapeutic attempts in this patient, using I-131 MIBG, are described. The metabolic basis of this phenomenon is discussed, and the importance of I-131 MIBG imaging in the detection of neural crest tumors is underlined

  17. Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice

    Science.gov (United States)

    Ye, Maoqing; Coldren, Chris; Liang, Xingqun; Mattina, Teresa; Goldmuntz, Elizabeth; Benson, D. Woodrow; Ivy, Dunbar; Perryman, M.B.; Garrett-Sinha, Lee Ann; Grossfeld, Paul

    2010-01-01

    Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an ∼7 Mb ‘cardiac critical region’ in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease. PMID:19942620

  18. Which patients with ES-SCLC are most likely to benefit from more aggressive radiotherapy: A secondary analysis of the Phase III CREST trial.

    Science.gov (United States)

    Slotman, Ben J; Faivre-Finn, Corinne; van Tinteren, Harm; Keijser, Astrid; Praag, John; Knegjens, Joost; Hatton, Matthew; van Dam, Iris; van der Leest, Annija; Reymen, Bart; Stigt, Jos; Haslett, Kate; Tripathi, Devashish; Smit, Egbert F; Senan, Suresh

    2017-06-01

    In ES-SCLC patients with residual intrathoracic disease after first-line chemotherapy, the addition of thoracic radiotherapy reduces the risk of intrathoracic recurrence, and improves 2-year survival. To identify patient subgroups for future trials investigating higher dose (extra)thoracic radiotherapy, we investigated the prognostic importance of number and sites of metastases in patients included in the CREST trial. Additional data on sites and numbers of metastases were collected from individual records of 260 patients from the top 9 recruiting centers in the randomized CREST trial (53% of 495 study patients), which compared thoracic radiotherapy (TRT) to no TRT in ES-SCLC patients after any response to chemotherapy. All patients received prophylactic cranial irradiation. The clinical characteristics and outcomes of the 260 patients analyzed here did not differ significantly from that of the other 235 patients included in the CREST trial, except that fewer patients had a WHO=0 performance status (24% vs 45%), and a higher proportion had WHO=2 (15% vs 5%; pradiotherapy in ES-SCLC should focus on patients with fewer than 3 distant metastases. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  19. HEART RATE RECOVERY AFTER EXERCISE AND NEURAL REGULATION OF HEART RATE VARIABILITY IN 30-40 YEAR OLD FEMALE MARATHON RUNNERS

    Directory of Open Access Journals (Sweden)

    Toshio Matsuoka

    2005-03-01

    Full Text Available The aim of the present study was to examine the effects of endurance training on heart rate (HR recovery after exercise and cardiac autonomic nervous system (ANS modulation in female marathon runners by comparing with untrained controls. Six female marathon runners (M group aged 32-40 years and eight age-matched untrained females (C group performed a maximum-effort treadmill running exercise. Maximal oxygen uptake (VO2max was measured during the exercise with a gas analyzer connected to subjects through a face mask. Heart rate, blood pressure and blood lactate were measured before and after the exercise. Rating of perceived exertion (RPE to the exercise was obtained immediately after the exercise. Holter ECG was recorded and analyzed with power spectral analysis of heart rate variability (HRV to investigate the cardiac ANS modulation. The M group had significantly higher VO2max, faster HR recovery after exercise, higher Mean RR, SDRR, HF power and lower LF/HF ratio at rest compared with the C group. The M group also presented greater percent decrease of blood pressure after exercise, although their blood pressure after exercise was higher than the C group. It is suggested that endurance training induced significant alterations in cardiac ANS modulation at rest and significant acceleration of HR recovery after exercise in female marathon runners. Faster HR recovery after exercise in the female marathon runners should result from their higher levels of HRV, higher aerobic capacity and exaggerated blood pressure response to exercise compared with untrained controls.

  20. Organochlorine contaminants and reproductive success of double-crested cormorants from Green Bay, Wisconsin, USA

    Science.gov (United States)

    Custer, T.W.; Custer, Christine M.; Hines, R.K.; Gutreuter, S.; Stromborg, K.L.; Allen, P. David; Melancon, M.J.

    1999-01-01

    In 1994 and 1995, nesting success of double-crested cormorants (Phalacrocorax auritus) was measured at Cat Island, in southern Green Bay, Lake Michigan, Wisconsin, USA. Sample eggs at pipping and unhatched eggs were collected and analyzed for organochlorines (including total polychlorinated biphenyls [PCBs] and DDE), hepatic microsomal ethoxyresorufin-O-dealkylase (EROD) activity in embryos, and eggshell thickness. Of 1,570 eggs laid, 32% did not hatch and 0.4% had deformed embryos. Of 632 chicks monitored from hatching to 12 d of age, 9% were missing or found dead; no deformities were observed. The PCB concentrations in sample eggs from clutches with deformed embryos (mean = 10.2 μg/g wet weight) and dead embryos (11.4 μg/g) were not significantly higher than concentrations in sample eggs from nests where all eggs hatched (12.1 μg/g). A logistic regression of hatching success versus DDE, dieldrin, and PCB concentrations in sibling eggs identified DDE and not dieldrin or PCBs as a significant risk factor. A logistic regression of hatching success versus DDE and eggshell thickness implicated DDE and not eggshell thickness as a significant risk factor. Even though the insecticide DDT was banned in the early 1970s, we suggest that DDE concentrations in double-crested cormorant eggs in Green Bay are still having an effect on reproduction in this species.

  1. Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft

    Science.gov (United States)

    2014-01-01

    Background This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. Methods This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. Results Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). Conclusions The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction. PMID:24957053

  2. Spatial ecology of the critically endangered Fijian crested iguana, Brachylophus vitiensis, in an extremely dense population: implications for conservation.

    Science.gov (United States)

    Morrison, Suzanne F; Biciloa, Pita; Harlow, Peter S; Keogh, J Scott

    2013-01-01

    The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs at extreme density at only one location, with estimates of >10,000 iguanas living on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture study over two wet seasons, investigating the spatial ecology and intraspecific interactions of the strictly arboreal Fijian crested iguana. This species exhibits moderate male-biased sexual size dimorphism, which has been linked in other lizard species to territoriality, aggression and larger male home ranges. We found that male Fijian crested iguanas exhibit high injury levels, indicative of frequent aggressive interactions. We did not find support for larger home range size in adult males relative to adult females, however male and female residents were larger than roaming individuals. Males with established home ranges also had larger femoral pores relative to body size than roaming males. Home range areas were small in comparison to those of other iguana species, and we speculate that the extreme population density impacts considerably on the spatial ecology of this population. There was extensive home range overlap within and between sexes. Intersexual overlap was greater than intrasexual overlap for both sexes, and continuing male-female pairings were observed among residents. Our results suggest that the extreme population density necessitates extensive home range overlap even though the underlying predictors of territoriality, such as male biased sexual size dimorphism and high aggression levels, remain. Our findings should be factored in to conservation management efforts for this species, particularly in captive breeding and translocation programs.

  3. Spatial ecology of the critically endangered Fijian crested iguana, Brachylophus vitiensis, in an extremely dense population: implications for conservation.

    Directory of Open Access Journals (Sweden)

    Suzanne F Morrison

    Full Text Available The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs at extreme density at only one location, with estimates of >10,000 iguanas living on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture study over two wet seasons, investigating the spatial ecology and intraspecific interactions of the strictly arboreal Fijian crested iguana. This species exhibits moderate male-biased sexual size dimorphism, which has been linked in other lizard species to territoriality, aggression and larger male home ranges. We found that male Fijian crested iguanas exhibit high injury levels, indicative of frequent aggressive interactions. We did not find support for larger home range size in adult males relative to adult females, however male and female residents were larger than roaming individuals. Males with established home ranges also had larger femoral pores relative to body size than roaming males. Home range areas were small in comparison to those of other iguana species, and we speculate that the extreme population density impacts considerably on the spatial ecology of this population. There was extensive home range overlap within and between sexes. Intersexual overlap was greater than intrasexual overlap for both sexes, and continuing male-female pairings were observed among residents. Our results suggest that the extreme population density necessitates extensive home range overlap even though the underlying predictors of territoriality, such as male biased sexual size dimorphism and high aggression levels, remain. Our findings should be factored in to conservation management efforts for this species, particularly in captive breeding and translocation programs.

  4. Spatial Ecology of the Critically Endangered Fijian Crested Iguana, Brachylophus vitiensis, in an Extremely Dense Population: Implications for Conservation

    Science.gov (United States)

    Morrison, Suzanne F.; Biciloa, Pita; Harlow, Peter S.; Keogh, J. Scott

    2013-01-01

    The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs at extreme density at only one location, with estimates of >10,000 iguanas living on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture study over two wet seasons, investigating the spatial ecology and intraspecific interactions of the strictly arboreal Fijian crested iguana. This species exhibits moderate male-biased sexual size dimorphism, which has been linked in other lizard species to territoriality, aggression and larger male home ranges. We found that male Fijian crested iguanas exhibit high injury levels, indicative of frequent aggressive interactions. We did not find support for larger home range size in adult males relative to adult females, however male and female residents were larger than roaming individuals. Males with established home ranges also had larger femoral pores relative to body size than roaming males. Home range areas were small in comparison to those of other iguana species, and we speculate that the extreme population density impacts considerably on the spatial ecology of this population. There was extensive home range overlap within and between sexes. Intersexual overlap was greater than intrasexual overlap for both sexes, and continuing male-female pairings were observed among residents. Our results suggest that the extreme population density necessitates extensive home range overlap even though the underlying predictors of territoriality, such as male biased sexual size dimorphism and high aggression levels, remain. Our findings should be factored in to conservation management efforts for this species, particularly in captive breeding and translocation programs. PMID:24019902

  5. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure.

    Science.gov (United States)

    Hamblet, Natasha S; Lijam, Nardos; Ruiz-Lozano, Pilar; Wang, Jianbo; Yang, Yasheng; Luo, Zhenge; Mei, Lin; Chien, Kenneth R; Sussman, Daniel J; Wynshaw-Boris, Anthony

    2002-12-01

    The murine dishevelled 2 (Dvl2) gene is an ortholog of the Drosophila segment polarity gene Dishevelled, a member of the highly conserved Wingless/Wnt developmental pathway. Dvl2-deficient mice were produced to determine the role of Dvl2 in mammalian development. Mice containing null mutations in Dvl2 present with 50% lethality in both inbred 129S6 and in a hybrid 129S6-NIH Black Swiss background because of severe cardiovascular outflow tract defects, including double outlet right ventricle, transposition of the great arteries and persistent truncus arteriosis. The majority of the surviving Dvl2(-/-) mice were female, suggesting that penetrance was influenced by sex. Expression of Pitx2 and plexin A2 was attenuated in Dvl2 null mutants, suggesting a defect in cardiac neural crest development during outflow tract formation. In addition, approximately 90% of Dvl2(-/-) mice have vertebral and rib malformations that affect the proximal as well as the distal parts of the ribs. These skeletal abnormalities were more pronounced in mice deficient for both Dvl1 and Dvl2. Somite differentiation markers used to analyze Dvl2(-/-) and Dvl1(-/-);Dvl2(-/-) mutant embryos revealed mildly aberrant expression of Uncx4.1, delta 1 and myogenin, suggesting defects in somite segmentation. Finally, 2-3% of Dvl2(-/-) embryos displayed thoracic spina bifida, while virtually all Dvl1/2 double mutant embryos displayed craniorachishisis, a completely open neural tube from the midbrain to the tail. Thus, Dvl2 is essential for normal cardiac morphogenesis, somite segmentation and neural tube closure, and there is functional redundancy between Dvl1 and Dvl2 in some phenotypes.

  6. Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk.

    Science.gov (United States)

    McCraty, Rollin; Shaffer, Fred

    2015-01-01

    Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems.

  7. Valvular Heart Disease in Heart Failure

    Directory of Open Access Journals (Sweden)

    Giuseppe MC Rosano

    2017-01-01

    Full Text Available Structural valvular heart disease may be the cause of heart failure or may worsen the clinical status of patients with heart failure. Heart failure may also develop in patients treated with valve surgery. Patients with heart failure with valvular heart disease are at increased risk of events including sudden cardiac death. Before considering intervention (surgical or percutaneous all patients should receive appropriate medical and device therapy taking into account that vasodilators must be used with caution in patients with severe aortic stenosis. Numerous percutaneous and/or hybrid procedures have been introduced in the past few years and they are changing the management of valvular heart disease. In patients with heart failure and valvular heart disease, either primary or functional, the whole process of decision-making should be staged through a comprehensive evaluation of the risk– benefit ratio of different treatment strategies and should be made by a multidisciplinary ‘heart team’ with a particular expertise in valvular heart disease. The heart team should include heart failure cardiologists, cardiac surgeons/structural valve interventionists, imaging specialists, anaesthetists, geriatricians and intensive care specialists. This article will review recent developments and distill practical guidance in the management of this important heart failure co-morbidity.

  8. Knowledge Mining from Clinical Datasets Using Rough Sets and Backpropagation Neural Network

    Directory of Open Access Journals (Sweden)

    Kindie Biredagn Nahato

    2015-01-01

    Full Text Available The availability of clinical datasets and knowledge mining methodologies encourages the researchers to pursue research in extracting knowledge from clinical datasets. Different data mining techniques have been used for mining rules, and mathematical models have been developed to assist the clinician in decision making. The objective of this research is to build a classifier that will predict the presence or absence of a disease by learning from the minimal set of attributes that has been extracted from the clinical dataset. In this work rough set indiscernibility relation method with backpropagation neural network (RS-BPNN is used. This work has two stages. The first stage is handling of missing values to obtain a smooth data set and selection of appropriate attributes from the clinical dataset by indiscernibility relation method. The second stage is classification using backpropagation neural network on the selected reducts of the dataset. The classifier has been tested with hepatitis, Wisconsin breast cancer, and Statlog heart disease datasets obtained from the University of California at Irvine (UCI machine learning repository. The accuracy obtained from the proposed method is 97.3%, 98.6%, and 90.4% for hepatitis, breast cancer, and heart disease, respectively. The proposed system provides an effective classification model for clinical datasets.

  9. 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.

  10. Heart Health - Brave Heart

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  11. Heart-Rate Variability—More than Heart Beats?

    Directory of Open Access Journals (Sweden)

    Gernot Ernst

    2017-09-01

    Full Text Available Heart-rate variability (HRV is frequently introduced as mirroring imbalances within the autonomous nerve system. Many investigations are based on the paradigm that increased sympathetic tone is associated with decreased parasympathetic tone and vice versa. But HRV is probably more than an indicator for probable disturbances in the autonomous system. Some perturbations trigger not reciprocal, but parallel changes of vagal and sympathetic nerve activity. HRV has also been considered as a surrogate parameter of the complex interaction between brain and cardiovascular system. Systems biology is an inter-disciplinary field of study focusing on complex interactions within biological systems like the cardiovascular system, with the help of computational models and time series analysis, beyond others. Time series are considered surrogates of the particular system, reflecting robustness or fragility. Increased variability is usually seen as associated with a good health condition, whereas lowered variability might signify pathological changes. This might explain why lower HRV parameters were related to decreased life expectancy in several studies. Newer integrating theories have been proposed. According to them, HRV reflects as much the state of the heart as the state of the brain. The polyvagal theory suggests that the physiological state dictates the range of behavior and psychological experience. Stressful events perpetuate the rhythms of autonomic states, and subsequently, behaviors. Reduced variability will according to this theory not only be a surrogate but represent a fundamental homeostasis mechanism in a pathological state. The neurovisceral integration model proposes that cardiac vagal tone, described in HRV beyond others as HF-index, can mirror the functional balance of the neural networks implicated in emotion–cognition interactions. Both recent models represent a more holistic approach to understanding the significance of HRV.

  12. Heart-Rate Variability-More than Heart Beats?

    Science.gov (United States)

    Ernst, Gernot

    2017-01-01

    Heart-rate variability (HRV) is frequently introduced as mirroring imbalances within the autonomous nerve system. Many investigations are based on the paradigm that increased sympathetic tone is associated with decreased parasympathetic tone and vice versa . But HRV is probably more than an indicator for probable disturbances in the autonomous system. Some perturbations trigger not reciprocal, but parallel changes of vagal and sympathetic nerve activity. HRV has also been considered as a surrogate parameter of the complex interaction between brain and cardiovascular system. Systems biology is an inter-disciplinary field of study focusing on complex interactions within biological systems like the cardiovascular system, with the help of computational models and time series analysis, beyond others. Time series are considered surrogates of the particular system, reflecting robustness or fragility. Increased variability is usually seen as associated with a good health condition, whereas lowered variability might signify pathological changes. This might explain why lower HRV parameters were related to decreased life expectancy in several studies. Newer integrating theories have been proposed. According to them, HRV reflects as much the state of the heart as the state of the brain. The polyvagal theory suggests that the physiological state dictates the range of behavior and psychological experience. Stressful events perpetuate the rhythms of autonomic states, and subsequently, behaviors. Reduced variability will according to this theory not only be a surrogate but represent a fundamental homeostasis mechanism in a pathological state. The neurovisceral integration model proposes that cardiac vagal tone, described in HRV beyond others as HF-index, can mirror the functional balance of the neural networks implicated in emotion-cognition interactions. Both recent models represent a more holistic approach to understanding the significance of HRV.

  13. Dietary intake of Deepwater Horizon oil-injected live food fish by double-crested cormorants resulted in oxidative stress.

    Science.gov (United States)

    Pritsos, Karen L; Perez, Cristina R; Muthumalage, Thivanka; Dean, Karen M; Cacela, Dave; Hanson-Dorr, Katie; Cunningham, Fred; Bursian, Steven J; Link, Jane E; Shriner, Susan; Horak, Katherine; Pritsos, Chris A

    2017-12-01

    The Deepwater Horizon oil spill released 134 million gallons of crude oil into the Gulf of Mexico making it the largest oil spill in US history and exposing fish, birds, and marine mammals throughout the Gulf of Mexico to its toxicity. Fish eating waterbirds such as the double-crested cormorant (Phalacrocorax auritus) were exposed to the oil both by direct contact with the oil and orally through preening and the ingestion of contaminated fish. This study investigated the effects of orally ingestedMC252 oil-contaminated live fish food by double-crested cormorants on oxidative stress. Total, reduced, and oxidized glutathione levels, superoxide dismutase and glutathione peroxidase activities, total antioxidant capacity and lipid peroxidation were assessed in the liver tissues of control and treated cormorants. The results suggest that ingestion of the oil-contaminated fish resulted in significant increase in oxidative stress in the liver tissues of these birds. The oil-induced increase in oxidative stress could have detrimental impacts on the bird's life-history. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer

    Science.gov (United States)

    Charité, Jeroen; McFadden, David G.; Merlo, Giorgio; Levi, Giovanni; Clouthier, David E.; Yanagisawa, Masashi; Richardson, James A.; Olson, Eric N.

    2001-01-01

    Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix–loop–helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified Dlx6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, Dlx6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that Dlx6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. PMID:11711438

  15. Understanding the Basis of Auriculocondylar Syndrome: Insights From Human and Mouse Genetic Studies

    Science.gov (United States)

    Clouthier, David E.; Passos Bueno, Maria Rita; Tavares, Andre L.P.; Lyonnet, Stanislas; Amiel, Jeanne; Gordon, Christopher T.

    2014-01-01

    Among human birth defect syndromes, malformations affecting the face are perhaps the most striking due to cultural and psychological expectations of facial shape. One such syndrome is auriculocondylar syndrome (ACS), in which patients present with defects in ear and mandible development. Affected structures arise from cranial neural crest cells, a population of cells in the embryo that reside in the pharyngeal arches and give rise to most of the bone, cartilage and connective tissue of the face. Recent studies have found that most cases of ACS arise from defects in signaling molecules associated with the endothelin signaling pathway. Disruption of this signaling pathway in both mouse and zebrafish results in loss of identity of neural crest cells of the mandibular portion of the first pharyngeal arch and the subsequent repatterning of these cells, leading to homeosis of lower jaw structures into more maxillary-like structures. These findings illustrate the importance of endothelin signaling in normal human craniofacial development and illustrate how clinical and basic science approaches can coalesce to improve our understanding of the genetic basis of human birth syndromes. Further, understanding the genetic basis for ACS that lies outside of known endothelin signaling components may help elucidate unknown aspects critical to the establishment of neural crest cell patterning during facial morphogenesis. PMID:24123988

  16. DECISION SUPPORT SYSTEM BASED ON SIGNS AND SYMPTOMS USING NEURAL NETWORKSFOR CONGENITAL HEART DISEASE DIAGNOSIS

    OpenAIRE

    ASHWINI PRAKASH TANDLE , PROF. A. R. WADHEKAR

    2018-01-01

    One of the important methods of data analysis is classification. Many real-world problems in various fields, such as business, science, industry, and medicine can be solved using a classification approach. Neural networks have emerged as an important tool for classification.

  17. Low-latitude scintillation occurrences around the equatorial anomaly crest over Indonesia

    Directory of Open Access Journals (Sweden)

    P. Abadi

    2014-01-01

    Full Text Available We investigated low-latitude ionospheric scintillation in Indonesia using two GPS receivers installed at Bandung (107.6° E, 6.9° S; magnetic latitude 17.5° S and Pontianak (109.3° E, 0.02° S; magnetic latitude 8.9° S. This study aimed to characterise climatological and directional ionospheric scintillation occurrences, which are useful not only for the physics of ionospheric irregularities but also for practical use in GNSS (global navigation satellite system-based navigation. We used the deployed instrument's amplitude scintillation (S4 index data from 2009, 2010, and 2011; the yearly SSN (sunspot-smoothed numbers were 3.1, 16.5, and 55.9, respectively. In summary, (1 scintillation occurrences in the post-sunset period (18:00–01:00 LT during equinox months (plasma bubble season at the two sites can be ascribed to the plasma bubble; (2 using directional analyses of the two sites, we found that the distribution of scintillation occurrences is generally concentrated between the two sites, indicating the average location of the EIA (equatorial ionisation anomaly crest; (3 scintillation occurrence enhancements for the two sites in field-aligned directions are herein reported for the first time by ground-based observation in a low-latitude region; (4 distribution of scintillation occurrences at Pontianak are concentrated in the southern sky, especially in the southwest direction, which is very likely associated with the plasma bubble tilted westward with increasing latitude; and (5 scintillation occurrence in the post-midnight period in the non-plasma-bubble season is the most intriguing variable occurring between the two sites (i.e. post-midnight scintillations are observed more at Bandung than Pontianak. Most of the post-midnight scintillations observed at Bandung are concentrated in the northern sky, with low elevation angles. This might be due to the amplitude of irregularities in certain directions, which may be effectively enhanced by

  18. Searching for TeV cosmic electrons with the CREST experiment

    International Nuclear Information System (INIS)

    Coutu, S.; Anderson, T.; Bower, C.; Gennaro, J.; Geske, M.; Mueller, D.; Musser, J.; Nutter, S.; Park, N.H.; Schubnell, M.; Tarle, G.; Wakely, S.; Yagi, A.

    2011-01-01

    The Cosmic Ray Electron Synchrotron Telescope (CREST) high-altitude balloon experiment is a pathfinding effort to detect for the first time multi-TeV cosmic-ray electrons. Such would be the markers of nearby cosmic accelerators, as energetic electrons from distant Galactic sources are expected to be depleted by radiative losses during interstellar transport. Electrons will be detected indirectly by the characteristic signature of their geomagnetic synchrotron losses, in the form of a burst of coaligned x-ray photons intersecting the plane of the instrument. Since the primary electron itself need not traverse the payload, an effective detection area is achieved that is several times the nominal 6.4 m 2 instrument. The payload is composed of an array of 1024 BaF2 crystals surrounded by a set of veto scintillator detectors. A long-duration balloon flight in Antarctica is planned for the 2011-12 season.

  19. Searching for TeV cosmic electrons with the CREST experiment

    Energy Technology Data Exchange (ETDEWEB)

    Coutu, S., E-mail: coutu@phys.psu.edu [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Anderson, T. [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Bower, C. [Physics Department, Indiana University, 117 Swain Hall West, Bloomington, IN 47405 (United States); Gennaro, J. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States); Geske, M. [Department of Physics, Pennsylvania State University, 104 Davey Laboratory, University Park, PA 16802 (United States); Mueller, D. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Musser, J. [Physics Department, Indiana University, 117 Swain Hall West, Bloomington, IN 47405 (United States); Nutter, S. [Department of Physics and Geology, Northern Kentucky University, Highland Heights, KY 41099 (United States); Park, N.H. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Schubnell, M.; Tarle, G. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States); Wakely, S. [Enrico Fermi Institute and Department of Physics, University of Chicago, 933 E. 56th St., Chicago, IL 60637 (United States); Yagi, A. [Department of Physics, University of Michigan, Randall Physics Laboratory, 500 E. University Ave, Ann Arbor, MI 48109 (United States)

    2011-06-15

    The Cosmic Ray Electron Synchrotron Telescope (CREST) high-altitude balloon experiment is a pathfinding effort to detect for the first time multi-TeV cosmic-ray electrons. Such would be the markers of nearby cosmic accelerators, as energetic electrons from distant Galactic sources are expected to be depleted by radiative losses during interstellar transport. Electrons will be detected indirectly by the characteristic signature of their geomagnetic synchrotron losses, in the form of a burst of coaligned x-ray photons intersecting the plane of the instrument. Since the primary electron itself need not traverse the payload, an effective detection area is achieved that is several times the nominal 6.4 m{sup 2} instrument. The payload is composed of an array of 1024 BaF2 crystals surrounded by a set of veto scintillator detectors. A long-duration balloon flight in Antarctica is planned for the 2011-12 season.

  20. Discharge coefficient of a rectangular sharp-edged broad-crested weir

    Directory of Open Access Journals (Sweden)

    Zachoval Zbyněk

    2014-06-01

    Full Text Available This paper is concerned with the determination of the relationship for the calculation of the discharge coefficient at free overflow over a rectangular sharp-edged broad-crested weir without lateral contraction. The determination was made on the basis of new measurement in a range of the relative thickness of the weir from 0.12 to 0.30 and newly in a large range of relative height of the weir extremely from 0.24 to 6.8 which greatly expands the application possibilities of low weirs. In addition, the effects of friction and surface tension on the value of the discharge coefficient were evaluated as well as the effect of the relative thickness of the weir. The new equation for discharge coefficient, expressed using the relative height of the weir, was subjected to verification made by an independent laboratory which confirmed its accuracy.

  1. Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-12-01

    How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

  2. NEURAL PAIN PATHWAY TRACING OF RABBIT ISCHEMIC HEART BY DOUBLE-RETROGRADE NEUROTRACING

    OpenAIRE

    Theodorus Dapamede; Obed Trinurcahyo Kinantyo Paundralingga; Masruroh Rahayu; Bambang Soemantri

    2015-01-01

    Background. Myocardial ischaemia occurs due to inadequate supply of oxygen to fulfill the myocardial tissue oxygen demand. This leads to angina pectoris or referred pain, whichhappens because of the inability of the brain to distinguish the visceral afferent inputs from the somatic afferent inputs since they run along a common pathway via the dorsal root ganglia. Aims. This study aims to distinguish specific areas of the rabbit heart that are projected to specific dorsal root ganglia, whic...

  3. An embryological point of view on associated congenital anomalies of children with Hirschsprung disease.

    Science.gov (United States)

    Slavikova, T; Zabojnikova, L; Babala, J; Varga, I

    2015-01-01

    The most common congenital gut motility disorder is the Hirschsprung disease (HSCR). This anomaly is characterized by absence of neural crest-derived enteric neuronal ganglia. The aim of our study was to analyze the relationship between HSCR and other congenital anomalies or malfunctions. We examined 130 patients with Hirschsprung disease from Slovakia for last 10 years. During patients examination we focused not only on morphological abnormalities, but also functional anomalies. The incidence of associated congenital anomalies in our patients with HSCR was 26.1 %. But if we add functional defects (hypothyroidism, malfunction in cellular immunity, neurological deficit) to the morphological congenital abnormalities, the rate of the patients with HSCR with additional defects achieves 50.1 %. Nine of our patients (6.9 %) had syndromic HSCR. The most frequent disorder (13.6 % of patients) was primary deficiency in cellular immunity. More than 12.3 % of patients with HSCR had genitourinary abnormalities, in 10.0 % of patients variable degree of psychomotor retardation was observed, and skeletal, muscle and limb anomalies involved 7.7 % of patients. In 7.6 % cases of patients we found congenital hypothyroidism (including 2 cases of agenesis of thyroid gland). More than 6.1 % of patients presented with an associated anomaly in gastrointestinal tract (mostly anorectal malformations). Up to 5.5 % patients had congenital anomaly of heart, 3.8 % had ophthalmic and 3.1 % had craniofacial anomalies. Down syndrome was the main diagnosis in 3.8 % patients. We discussed  the relationship between HSCR and other anomalies, which are probably caused by abnormal migration, proliferation, or differentiation, of neural crest cells during embryogenesis (Tab. 1, Fig. 2, Ref. 75).

  4. Cardiac Arrhythmia Classification by Multi-Layer Perceptron and Convolution Neural Networks

    Directory of Open Access Journals (Sweden)

    Shalin Savalia

    2018-05-01

    Full Text Available The electrocardiogram (ECG plays an imperative role in the medical field, as it records heart signal over time and is used to discover numerous cardiovascular diseases. If a documented ECG signal has a certain irregularity in its predefined features, this is called arrhythmia, the types of which include tachycardia, bradycardia, supraventricular arrhythmias, and ventricular, etc. This has encouraged us to do research that consists of distinguishing between several arrhythmias by using deep neural network algorithms such as multi-layer perceptron (MLP and convolution neural network (CNN. The TensorFlow library that was established by Google for deep learning and machine learning is used in python to acquire the algorithms proposed here. The ECG databases accessible at PhysioBank.com and kaggle.com were used for training, testing, and validation of the MLP and CNN algorithms. The proposed algorithm consists of four hidden layers with weights, biases in MLP, and four-layer convolution neural networks which map ECG samples to the different classes of arrhythmia. The accuracy of the algorithm surpasses the performance of the current algorithms that have been developed by other cardiologists in both sensitivity and precision.

  5. Cardiac Arrhythmia Classification by Multi-Layer Perceptron and Convolution Neural Networks.

    Science.gov (United States)

    Savalia, Shalin; Emamian, Vahid

    2018-05-04

    The electrocardiogram (ECG) plays an imperative role in the medical field, as it records heart signal over time and is used to discover numerous cardiovascular diseases. If a documented ECG signal has a certain irregularity in its predefined features, this is called arrhythmia, the types of which include tachycardia, bradycardia, supraventricular arrhythmias, and ventricular, etc. This has encouraged us to do research that consists of distinguishing between several arrhythmias by using deep neural network algorithms such as multi-layer perceptron (MLP) and convolution neural network (CNN). The TensorFlow library that was established by Google for deep learning and machine learning is used in python to acquire the algorithms proposed here. The ECG databases accessible at PhysioBank.com and kaggle.com were used for training, testing, and validation of the MLP and CNN algorithms. The proposed algorithm consists of four hidden layers with weights, biases in MLP, and four-layer convolution neural networks which map ECG samples to the different classes of arrhythmia. The accuracy of the algorithm surpasses the performance of the current algorithms that have been developed by other cardiologists in both sensitivity and precision.

  6. Validation of measured poleward TEC gradient using multi-station GPS with Artificial Neural Network based TEC model in low latitude region for developing predictive capability of ionospheric scintillation

    Science.gov (United States)

    Sur, D.; Paul, A.

    2017-12-01

    The equatorial ionosphere shows sharp diurnal and latitudinal Total Electron Content (TEC) variations over a major part of the day. Equatorial ionosphere also exhibits intense post-sunset ionospheric irregularities. Accurate prediction of TEC in these low latitudes is not possible from standard ionospheric models. An Artificial Neural Network (ANN) based Vertical TEC (VTEC) model has been designed using TEC data in low latitude Indian longitude sector for accurate prediction of VTEC. GPS TEC data from the stations Calcutta (22.58°N, 88.38°E geographic, magnetic dip 32°), Baharampore (24.09°N, 88.25°E geographic, magnetic dip 35°) and Siliguri (26.72°N, 88.39°E geographic; magnetic dip 40°) are used as training dataset for the duration of January 2007-September 2011. Poleward VTEC gradients from northern EIA crest to region beyond EIA crest have been calculated from measured VTEC and compared with that obtained from ANN based VTEC model. TEC data from Calcutta and Siliguri are used to compute VTEC gradients during April 2013 and August-September 2013. It has been observed that poleward VTEC gradient computed from ANN based TEC model has shown good correlation with measured values during vernal and autumnal equinoxes of high solar activity periods of 2013. Possible correlation between measured poleward TEC gradients and post-sunset scintillations (S4 ≥ 0.4) from northern crest of EIA has been observed in this paper. From the observation, a suitable threshold poleward VTEC gradient has been proposed for possible occurrence of post-sunset scintillations at northern crest of EIA along 88°E longitude. Poleward VTEC gradients obtained from ANN based VTEC model are used to forecast possible ionospheric scintillation after post-sunset period using the threshold value. It has been observed that these predicted VTEC gradients obtained from ANN based VTEC model can forecast post-sunset L-band scintillation with an accuracy of 67% to 82% in this dynamic low latitude

  7. Distribution and chronotropic effects of serotonin in the zebrafish heart.

    Science.gov (United States)

    Stoyek, Matthew R; Jonz, Michael G; Smith, Frank M; Croll, Roger P

    2017-09-01

    Several lines of evidence suggest that serotonin (5-HT) has a regulatory role in cardiovascular function from embryogenesis through adulthood. However, the reported actions of 5-HT are often contradictory and include bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction. Clarifying such cardiac effects requires further research and may benefit from utilizing a model simpler than the mammalian hearts traditionally used in these studies. In the present study, we describe the cardiac distribution and chronotropic responses of 5-HT in the zebrafish heart. A combined anatomical, electrophysiological, and pharmacological approach was used to investigate the involvement of 5-HT pathways, and to compare neural and direct myocardial pathways of biological action. Immunohistochemical methods revealed 5-HT in endocardial cells, glial-like cells, and intracardiac neurons in the atrium. Electrocardiogram (ECG) recordings combined with the administration of pharmacological agents demonstrated that 5-HT acted predominantly through direct myocardial pathways resulting in a reduction of heart rate. Overall, the results of this study contribute significant advances in the establishment of the zebrafish as a new model for studies of the role of 5-HT in autonomic cardiac control. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Age-related changes in molar topography and shearing crest length in a wild population of mountain Gorillas from Volcanoes National Park, Rwanda.

    Science.gov (United States)

    Glowacka, Halszka; McFarlin, Shannon C; Catlett, Kierstin K; Mudakikwa, Antoine; Bromage, Timothy G; Cranfield, Michael R; Stoinski, Tara S; Schwartz, Gary T

    2016-05-01

    Great ape teeth must remain functional over long lifespans. The molars of the most folivorous apes, the mountain gorillas, must maintain shearing function for 40+ years while the animals consume large quantities of mechanically challenging foods. While other folivorous primates experience dental senescence, which compromises their occlusal surfaces and affects their reproductive success as they age, it is unknown whether dental senescence also occurs in mountain gorillas. In this article, we quantified and evaluated how mountain gorilla molars change throughout their long lifespans. We collected high-resolution replicas of M(1)s (n = 15), M(2)s (n = 13), and M(3)s (n = 11) from a cross-sectional sample of wild mountain gorilla skeletons from the Virunga Volcanoes, ranging in age from 4 to 43 years. We employed dental topographic analyses to track how aspects of occlusal slope, angularity, relief index, and orientation patch count rotated change with age. In addition, we measured the relative length of shearing crests in two- and three-dimensions. Occlusal topography was found to decrease, while 2D relative shearing crest length increased, and 3D relative crest lengths were maintained with age. Our findings indicate that shearing function is maintained throughout the long lifetimes of mountain gorillas. Unlike the dental senescence experienced by other folivorous primates, mountain gorillas do not appear to possess senesced molars despite their long lifetimes, mechanically challenging diets, and decreases in occlusal topography with age. © 2016 Wiley Periodicals, Inc.

  9. Entertainment Capture through Heart Rate Activity in Physical Interactive Playgrounds

    DEFF Research Database (Denmark)

    Yannakakis, Georgios; Hallam, John; Lund, Henrik Hautop

    2008-01-01

    children’s physiological signals, an estimator of the degree to which games provided by the playground engage the players. For this purpose children’s heart rate (HR) signals, and their expressed preferences of how much “fun” particular game variants are, are obtained from experiments using games...... that predict reported entertainment preferences given HR features. These models are expressed as artificial neural networks and are demonstrated and evaluated on two Playware games and two control tasks requiring physical activity. The best network is able to correctly match expressed preferences in 64...

  10. 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.

  11. Convolution neural-network-based detection of lung structures

    Science.gov (United States)

    Hasegawa, Akira; Lo, Shih-Chung B.; Freedman, Matthew T.; Mun, Seong K.

    1994-05-01

    Chest radiography is one of the most primary and widely used techniques in diagnostic imaging. Nowadays with the advent of digital radiology, the digital medical image processing techniques for digital chest radiographs have attracted considerable attention, and several studies on the computer-aided diagnosis (CADx) as well as on the conventional image processing techniques for chest radiographs have been reported. In the automatic diagnostic process for chest radiographs, it is important to outline the areas of the lungs, the heart, and the diaphragm. This is because the original chest radiograph is composed of important anatomic structures and, without knowing exact positions of the organs, the automatic diagnosis may result in unexpected detections. The automatic extraction of an anatomical structure from digital chest radiographs can be a useful tool for (1) the evaluation of heart size, (2) automatic detection of interstitial lung diseases, (3) automatic detection of lung nodules, and (4) data compression, etc. Based on the clearly defined boundaries of heart area, rib spaces, rib positions, and rib cage extracted, one should be able to use this information to facilitate the tasks of the CADx on chest radiographs. In this paper, we present an automatic scheme for the detection of lung field from chest radiographs by using a shift-invariant convolution neural network. A novel algorithm for smoothing boundaries of lungs is also presented.

  12. The man who feels two hearts: the different pathways of interoception.

    Science.gov (United States)

    Couto, Blas; Salles, Alejo; Sedeño, Lucas; Peradejordi, Margarita; Barttfeld, Pablo; Canales-Johnson, Andrés; Dos Santos, Yamil Vidal; Huepe, David; Bekinschtein, Tristán; Sigman, Mariano; Favaloro, Roberto; Manes, Facundo; Ibanez, Agustin

    2014-09-01

    Recent advances in neuroscience have provided new insights into the understanding of heart-brain interaction and communication. Cardiac information to the brain relies on two pathways, terminating in the insular cortex (IC) and anterior cingulate cortex (ACC), along with the somatosensory cortex (S1-S2). Interoception relying on these neuroanatomical pathways has been shown to modulate social cognition. We report the case study of C.S., a patient with an 'external heart' (an extracorporeal left-univentricular cardiac assist device, LVAD). The patient was assessed with neural/behavioral measures of cardiac interoception complemented by neuropsychological and social cognition measures. The patient's performance on the interoception task (heartbeat detection) seemed to be guided by signals from the artificial LVAD, which provides a somatosensory beat rather than by his endogenous heart. Cortical activity (HEP, heartbeat-evoked potential) was found decreased in comparison with normal volunteers, particularly during interoceptive states. The patient accurately performed several cognitive tasks, except for interoception-related social cognition domains (empathy, theory of mind and decision making). This evidence suggests an imbalance in the patient's cardiac interoceptive pathways that enhances sensation driven by the artificial pump over that from the cardiac vagal-IC/ACC pathway. A patient with two hearts, one endogenous and one artificial, presents a unique opportunity to explore models of interoception and heart-brain interaction. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Rho-associated kinase is a therapeutic target in neuroblastoma.

    Science.gov (United States)

    Dyberg, Cecilia; Fransson, Susanne; Andonova, Teodora; Sveinbjörnsson, Baldur; Lännerholm-Palm, Jessika; Olsen, Thale K; Forsberg, David; Herlenius, Eric; Martinsson, Tommy; Brodin, Bertha; Kogner, Per; Johnsen, John Inge; Wickström, Malin

    2017-08-08

    Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN -driven neuroblastoma growth in TH- MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

  14. A new crested pterosaur from the Early Cretaceous of Spain: the first European tapejarid (Pterodactyloidea: Azhdarchoidea.

    Directory of Open Access Journals (Sweden)

    Romain Vullo

    Full Text Available BACKGROUND: The Tapejaridae is a group of unusual toothless pterosaurs characterized by bizarre cranial crests. From a paleoecological point of view, frugivorous feeding habits have often been suggested for one of its included clades, the Tapejarinae. So far, the presence of these intriguing flying reptiles has been unambiguously documented from Early Cretaceous sites in China and Brazil, where pterosaur fossils are less rare and fragmentary than in similarly-aged European strata. METHODOLOGY/PRINCIPAL FINDINGS: Europejara olcadesorum gen. et sp. nov. is diagnosed by a unique combination of characters including an unusual caudally recurved dentary crest. It represents the oldest known member of Tapejaridae and the oldest known toothless pterosaur. The new taxon documents the earliest stage of the acquisition of this anatomical feature during the evolutionary history of the Pterodactyloidea. This innovation may have been linked to the development of new feeding strategies. CONCLUSION/SIGNIFICANCE: The discovery of Europejara in the Barremian of the Iberian Peninsula reveals an earlier and broader global distribution of tapejarids, suggesting a Eurasian origin of this group. It adds to the poorly known pterosaur fauna of the Las Hoyas locality and contributes to a better understanding of the paleoecology of this Konservat-Lagerstätte. Finally, the significance of a probable contribution of tapejarine tapejarids to the early angiosperm dispersal is discussed.

  15. [Variability of heart rhythm in dynamic study of the psychovegetative relationship in neurogenic syncope].

    Science.gov (United States)

    Musaeva, Z A; Khaspekova, N B; Veĭn, A M

    2001-01-01

    Physiological changes accompanying syncopes of neural origin (SNO) in patients with psychovegetative syndrome are still insufficiently studied. The data concerning the role of the autonomic nervous system are discrepant. Heart rate variability was analyzed in 68 patients with SNO in a supine position and during the active 20-min orthostatic test taking into account the heart rate components of very low frequency (VLF, an index of cerebral sympathetic activity) and high frequency (HF, a marker of vagal modulation). Steady growth of the VLF and progressive decrease in the LF within 15-20 min of the orthostasis were observed in all the patients (n = 33), who fainted after this period. The predominance of the VLF in the heart rate power spectra was correlated with a high level of anxiety. It is suggested that this fact indicates the stable cerebral sympathetic activation resulting in a baroreceptor dysfunction, i.e., a failure of vasomotor regulation in patients with SNO.

  16. Experiment list: SRX743843 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and ch... and death. This tumor is the most common intraabdominal malignancy of childhood,

  17. Experiment list: SRX743827 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and ch... and death. This tumor is the most common intraabdominal malignancy of childhood,

  18. Could Cells from Your Nose Fix Your Heart? Transplantation of Olfactory Stem Cells in a Rat Model of Cardiac Infarction

    Directory of Open Access Journals (Sweden)

    Cameron McDonald

    2010-01-01

    Full Text Available This study examines the hypothesis that multipotent olfactory mucosal stem cells could provide a basis for the development of autologous cell transplant therapy for the treatment of heart attack. In humans, these cells are easily obtained by simple biopsy. Neural stem cells from the olfactory mucosa are multipotent, with the capacity to differentiate into developmental fates other than neurons and glia, with evidence of cardiomyocyte differentiation in vitro and after transplantation into the chick embryo. Olfactory stem cells were grown from rat olfactory mucosa. These cells are propagated as neurosphere cultures, similar to other neural stem cells. Olfactory neurospheres were grown in vitro, dissociated into single cell suspensions, and transplanted into the infarcted hearts of congeneic rats. Transplanted cells were genetically engineered to express green fluorescent protein (GFP in order to allow them to be identified after transplantation. Functional assessment was attempted using echocardiography in three groups of rats: control, unoperated; infarct only; infarcted and transplanted. Transplantation of neurosphere-derived cells from adult rat olfactory mucosa appeared to restore heart rate with other trends towards improvement in other measures of ventricular function indicated. Importantly, donor-derived cells engrafted in the transplanted cardiac ventricle and expressed cardiac contractile proteins.

  19. Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

    Science.gov (United States)

    Vilain, Katherine R; Magnuson, Elizabeth A; Li, Haiyan; Clark, Wayne M; Begg, Richard J; Sam, Albert D; Sternbergh, W Charles; Weaver, Fred A; Gray, William A; Voeks, Jenifer H; Brott, Thomas G; Cohen, David J

    2012-09-01

    The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes

  20. Classification of Fetal Heart Rate Tracings Based on Wavelet-Transform & Self-Organizing Map Neural Networks

    National Research Council Canada - National Science Library

    Vasios, G

    2001-01-01

    .... We demonstrate that it is possible to distinguish between healthy subjects and acidemic fetuses by way of wavelet transform analysis of the fetal heart rate recordings and fetal pulse oximetry (FSpO2...