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Sample records for embryonic morphogen nodal

  1. The embryonic morphogen, Nodal, is associated with channel-like structures in human malignant melanoma xenografts.

    PubMed

    McAllister, Josephine C; Zhan, Qian; Weishaupt, Carsten; Hsu, Mei-Yu; Murphy, George F

    2010-04-01

    Formation of channel-like structures, also termed vasculogenic mimicry (VM), describes the ability of aggressive melanoma cells to form PAS-positive anastomosing structures that correlate with tumor virulence. This phenomenon may indicate differentiation plasticity, a feature melanoma cells may share with stem cells in the developing embryo. Recent studies have indicated that VM and tumorigenicity of human malignant melanoma may depend on the signaling pathways of an embryonic morphogen, Nodal. However, given the secretory nature of Nodal protein and melanoma cell heterogeneity, it remains unclear whether the Nodal-expressing cells participate directly or indirectly in VM that is potentially related to tumorigenic growth. We have developed a humanized murine xenograft model in which developing human melanomas may be sequentially studied during early stages of tumorigenic growth within a physiological human dermal microenvironment. Nodal protein localized diffusely to melanoma cell membranes, with occasional foci of accentuated reactivity in patterns suggestive of channel formation. Similar findings were detected in a limited number of patient-derived tumors. In situ hybridization confirmed Nodal mRNA to be restricted to tumor cells within xenografts that formed arborizing networks in patterns consistent with VM. These data indicate that Nodal gene expression is associated with formation of VM-like structures in a physiologically relevant model of human melanoma tumorigenesis, and further support a key role for Nodal expression in the formation of channel-like structures. The humanized xenograft model should be useful in future studies to define the mechanistic pathways responsible for VM and melanoma progression.

  2. Embryonic Morphogen Nodal Is Associated with Progression and Poor Prognosis of Hepatocellular Carcinoma

    PubMed Central

    Jia, Wei-Dong; Xu, Ge-Liang; Ma, Jin-Liang; Ren, Yun; Chen, Hao; Sun, Si-Nan; Huang, Mei; Li, Jian-Sheng

    2014-01-01

    Background Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear. Methods We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters. Results Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC. Conclusions Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis

  3. Response to Nodal morphogen gradient is determined by the kinetics of target gene induction

    PubMed Central

    Dubrulle, Julien; Jordan, Benjamin M; Akhmetova, Laila; Farrell, Jeffrey A; Kim, Seok-Hyung; Solnica-Krezel, Lilianna; Schier, Alexander F

    2015-01-01

    Morphogen gradients expose cells to different signal concentrations and induce target genes with different ranges of expression. To determine how the Nodal morphogen gradient induces distinct gene expression patterns during zebrafish embryogenesis, we measured the activation dynamics of the signal transducer Smad2 and the expression kinetics of long- and short-range target genes. We found that threshold models based on ligand concentration are insufficient to predict the response of target genes. Instead, morphogen interpretation is shaped by the kinetics of target gene induction: the higher the rate of transcription and the earlier the onset of induction, the greater the spatial range of expression. Thus, the timing and magnitude of target gene expression can be used to modulate the range of expression and diversify the response to morphogen gradients. DOI: http://dx.doi.org/10.7554/eLife.05042.001 PMID:25869585

  4. Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness.

    PubMed

    Topczewska, Jolanta M; Postovit, Lynne-Marie; Margaryan, Naira V; Sam, Anthony; Hess, Angela R; Wheaton, William W; Nickoloff, Brian J; Topczewski, Jacek; Hendrix, Mary J C

    2006-08-01

    Bidirectional cellular communication is integral to both cancer progression and embryological development. In addition, aggressive tumor cells are phenotypically plastic, sharing many properties with embryonic cells. Owing to the similarities between these two types of cells, the developing zebrafish can be used as a biosensor for tumor-derived signals. Using this system, we show that aggressive melanoma cells secrete Nodal (a potent embryonic morphogen) and consequently can induce ectopic formation of the embryonic axis. We further show that Nodal is present in human metastatic tumors, but not in normal skin, and thus may be involved in melanoma pathogenesis. Inhibition of Nodal signaling reduces melanoma cell invasiveness, colony formation and tumorigenicity. Nodal inhibition also promotes the reversion of melanoma cells toward a melanocytic phenotype. These data suggest that Nodal signaling has a key role in melanoma cell plasticity and tumorigenicity, thereby providing a previously unknown molecular target for regulating tumor progression. PMID:16892036

  5. Inhibitory morphogens and monopodial branching of the embryonic chicken lung

    PubMed Central

    Gleghorn, Jason P.; Kwak, Jiyong; Pavlovich, Amira L.; Nelson, Celeste M.

    2012-01-01

    Branching morphogenesis generates a diverse array of epithelial patterns, including dichotomous and monopodial geometries. Dichotomous branching can be instructed by concentration gradients of epithelial-derived inhibitory morphogens, including transforming growth factor-β (TGFβ), which is responsible for ramification of the pubertal mammary gland. Here, we investigated the role of autocrine inhibitory morphogens in monopodial branching morphogenesis of the embryonic chicken lung. Computational modeling and experiments using cultured organ explants each separately revealed that monopodial branching patterns cannot be specified by a single epithelial-derived autocrine morphogen gradient. Instead, signaling via TGFβ1 and bone morphogenetic protein-4 (BMP4) differentially affect the rates of branching and growth of the airways. Allometric analysis revealed that development of the epithelial tree obeys power-law dynamics; TGFβ1 and BMP4 have distinct but reversible effects on the scaling coefficient of the power law. These data suggest that although autocrine inhibition cannot specify monopodial branching, inhibitory morphogens define the dynamics of lung morphogenesis. PMID:22410853

  6. A Mechanochemical Model for Embryonic Pattern Formation: Coupling Tissue Mechanics and Morphogen Expression

    PubMed Central

    Mercker, Moritz; Hartmann, Dirk; Marciniak-Czochra, Anna

    2013-01-01

    Motivated by recent experimental findings, we propose a novel mechanism of embryonic pattern formation based on coupling of tissue curvature with diffusive signaling by a chemical factor. We derive a new mathematical model using energy minimization approach and show that the model generates a variety of morphogen and curvature patterns agreeing with experimentally observed structures. The mechanism proposed transcends the classical Turing concept which requires interactions between two morphogens with a significantly different diffusivity. Our studies show how biomechanical forces may replace the elusive long-range inhibitor and lead to formation of stable spatially heterogeneous structures without existence of chemical prepatterns. We propose new experimental approaches to decisively test our central hypothesis that tissue curvature and morphogen expression are coupled in a positive feedback loop. PMID:24376555

  7. Graded Nodal/Activin Signaling Titrates Conversion of Quantitative Phospho-Smad2 Levels into Qualitative Embryonic Stem Cell Fate Decisions

    PubMed Central

    Orlov, Yuriy Lvovich; Yit, Le Yau; Yang, Henry; Ang, Lay Teng; Poellinger, Lorenz; Lim, Bing

    2011-01-01

    Nodal and Activin are morphogens of the TGFbeta superfamily of signaling molecules that direct differential cell fate decisions in a dose- and distance-dependent manner. During early embryonic development the Nodal/Activin pathway is responsible for the specification of mesoderm, endoderm, node, and mesendoderm. In contradiction to this drive towards cellular differentiation, the pathway also plays important roles in the maintenance of self-renewal and pluripotency in embryonic and epiblast stem cells. The molecular basis behind stem cell interpretation of Nodal/Activin signaling gradients and the undertaking of disparate cell fate decisions remains poorly understood. Here, we show that any perturbation of endogenous signaling levels in mouse embryonic stem cells leads to their exit from self-renewal towards divergent differentiation programs. Increasing Nodal signals above basal levels by direct stimulation with Activin promotes differentiation towards the mesendodermal lineages while repression of signaling with the specific Nodal/Activin receptor inhibitor SB431542 induces trophectodermal differentiation. To address how quantitative Nodal/Activin signals are translated qualitatively into distinct cell fates decisions, we performed chromatin immunoprecipitation of phospho-Smad2, the primary downstream transcriptional factor of the Nodal/Activin pathway, followed by massively parallel sequencing, and show that phospho-Smad2 binds to and regulates distinct subsets of target genes in a dose-dependent manner. Crucially, Nodal/Activin signaling directly controls the Oct4 master regulator of pluripotency by graded phospho-Smad2 binding in the promoter region. Hence stem cells interpret and carry out differential Nodal/Activin signaling instructions via a corresponding gradient of Smad2 phosphorylation that selectively titrates self-renewal against alternative differentiation programs by direct regulation of distinct target gene subsets and Oct4 expression. PMID

  8. Human Cerberus Prevents Nodal-Receptor Binding, Inhibits Nodal Signaling, and Suppresses Nodal-Mediated Phenotypes

    PubMed Central

    Aykul, Senem; Ni, Wendi; Mutatu, Washington; Martinez-Hackert, Erik

    2015-01-01

    The Transforming Growth Factor-ß (TGFß) family ligand Nodal is an essential embryonic morphogen that is associated with progression of breast and other cancers. It has therefore been suggested that Nodal inhibitors could be used to treat breast cancers where Nodal plays a defined role. As secreted antagonists, such as Cerberus, tightly regulate Nodal signaling during embryonic development, we undertook to produce human Cerberus, characterize its biochemical activities, and determine its effect on human breast cancer cells. Using quantitative methods, we investigated the mechanism of Nodal signaling, we evaluated binding of human Cerberus to Nodal and other TGFß family ligands, and we characterized the mechanism of Nodal inhibition by Cerberus. Using cancer cell assays, we examined the ability of Cerberus to suppress aggressive breast cancer cell phenotypes. We found that human Cerberus binds Nodal with high affinity and specificity, blocks binding of Nodal to its signaling partners, and inhibits Nodal signaling. Moreover, we showed that Cerberus profoundly suppresses migration, invasion, and colony forming ability of Nodal expressing and Nodal supplemented breast cancer cells. Taken together, our studies provide mechanistic insights into Nodal signaling and Nodal inhibition with Cerberus and highlight the potential value of Cerberus as anti-Nodal therapeutic. PMID:25603319

  9. The Role of Regulated mRNA Stability in Establishing Bicoid Morphogen Gradient in Drosophila Embryonic Development

    PubMed Central

    Liu, Wei; Niranjan, Mahesan

    2011-01-01

    The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner. PMID:21949782

  10. Expression of Nodal and Nodal Receptors in Prostate Stem Cells and Prostate Cancer Cells: Autocrine Effects on Cell Proliferation and Migration

    PubMed Central

    Vo, BaoHan T.; Khan, Shafiq A.

    2010-01-01

    BACKGROUND Nodal, a TGFβ like growth factor, functions as an embryonic morphogen that maintains the pluripotency of embryonic stem cells. Nodal has been implicated in cancer progression; however, there is no information on expression and functions of Nodal in prostate cancer. In this study, we have investigated the expression of Nodal, its receptors, and its effects on proliferation and migration of human prostate cells. METHODS RT-PCR, qPCR, and Western blot analyses were performed to analyze expression of Nodal and Nodal receptors and its effects on phosphorylation of Smad2/3 in prostate cells. The effects on proliferation and migration were determined by 3H-Thymidine incorporation and cell migration assays in the presence or absence of Nodal receptor inhibitor (SB431542). RESULTS Nodal was highly expressed in WPE, DU145, LNCaP, and LNCaP-C81 cells with low expression in RWPE1 and RWPE2 cells, but not in PREC, PC3 and PC3M cells. Nodal receptors are expressed at varying levels in all prostate cells. Treatment with exogenous Nodal induced phosphorylation of Smad2/3 in WPE, DU145, and PC3 cells, which was blocked by SB431542. Nodal dose-dependently inhibited proliferation of WPE, RWPE1 and DU145 cells, but not LNCaP and PC3 cells. Nodal induced cell migration in PC3 cells, which was inhibited by SB431542; Nodal had no effect on cell migration in WPE and DU145 cells. The effects of Nodal on cell proliferation and migration are mediated via ALK4 and ActRII/ActRIIB receptors and Smad 2/3 phosphorylation. CONCLUSIONS Nodal may function as an autocrine regulator of proliferation and migration of prostate cancer cells. PMID:21557273

  11. BMP Inhibition in Seminomas Initiates Acquisition of Pluripotency via NODAL Signaling Resulting in Reprogramming to an Embryonal Carcinoma

    PubMed Central

    Nettersheim, Daniel; Jostes, Sina; Sharma, Rakesh; Schneider, Simon; Hofmann, Andrea; Ferreira, Humberto J.; Hoffmann, Per; Kristiansen, Glen; Esteller, Manel B.; Schorle, Hubert

    2015-01-01

    Type II germ cell cancers (GCC) can be subdivided into seminomas and non-seminomas. Seminomas are similar to carcinoma in situ (CIS) cells, the common precursor of type II GCCs, with regard to epigenetics and expression, while embryonal carcinomas (EC) are totipotent and differentiate into teratomas, yolk-sac tumors and choriocarcinomas. GCCs can present as seminomas with a non-seminoma component, raising the question if a CIS gives rise to seminomas and ECs at the same time or whether seminomas can be reprogrammed to ECs. In this study, we utilized the seminoma cell line TCam-2 that acquires an EC-like status after xenografting into the murine flank as a model for a seminoma to EC transition and screened for factors initiating and driving this process. Analysis of expression and DNA methylation dynamics during transition of TCam-2 revealed that many pluripotency- and reprogramming-associated genes were upregulated while seminoma-markers were downregulated. Changes in expression level of 53 genes inversely correlated to changes in DNA methylation. Interestingly, after xenotransplantation 6 genes (GDF3, NODAL, DNMT3B, DPPA3, GAL, AK3L1) were rapidly induced, followed by demethylation of their genomic loci, suggesting that these 6 genes are poised for expression driving the reprogramming. We demonstrate that inhibition of BMP signaling is the initial event in reprogramming, resulting in activation of the pluripotency-associated genes and NODAL signaling. We propose that reprogramming of seminomas to ECs is a multi-step process. Initially, the microenvironment causes inhibition of BMP signaling, leading to induction of NODAL signaling. During a maturation phase, a fast acting NODAL loop stimulates its own activity and temporarily inhibits BMP signaling. During the stabilization phase, a slow acting NODAL loop, involving WNTs re-establishes BMP signaling and the pluripotency circuitry. In parallel, DNMT3B-driven de novo methylation silences seminoma-associated genes

  12. Encapsulation of bone morphogenic protein-2 with Cbfa1-overexpressing osteogenic cells derived from human embryonic stem cells in hydrogel accelerates bone tissue regeneration.

    PubMed

    Kim, Min Jung; Park, Ji Sun; Kim, Sinae; Moon, Sung-Hwan; Yang, Han Na; Park, Keun-Hong; Chung, Hyung-Min

    2011-08-01

    Bone tissue defects caused by trauma and disease are significant problems in orthopedic surgery. Human embryonic stem cells (hESCs) hold great promise for the treatment of bone tissue disease in regenerative medicine. In this study, we have established an effective method for the differentiation of osteogenic cells derived from hESCs using a lentiviral vector containing the transcription factor Cbfa1. Differentiation was initiated in embryoid body formation of Cbfa1-expressing hESCs, resulting in a highly purified population of osteogenic cells based on flow cytometric analysis. These cells also showed characteristics of osteogenic cells in vitro, as determined by reverse-transcription (RT)-polymerase chain reaction and immunocytochemistry using osteoblast-specific markers. We also evaluated the regenerative potential of Cbfa1-expressing cells derived from hESCs (hESC-CECs) compared with hESCs and the osteogenic effects of bone morphogenic protein-2 (BMP2) encapsulated in thermoreversible hydrogel in vivo. hESC-CECs were embedded in hydrogel constructs enriched with BMP2 to promote bone regeneration. We observed prominent mineralization and the formation of nodule-like structures using von Kossa and alizarin red S staining. In addition, the expression patterns of osteoblast-specific genes were verified by RT-polymerase chain reaction, and immunohistochemical analysis revealed that collagen type 1 and Cbfa1 were highly expressed in hESC-CECs compared with other cell types. Taken together, our results suggest that encapsulation of hESC-CECs with BMP2 in hydrogel constructs appears to be a promising method to enhance the in vitro osteoblastic differentiation and in vivo osteogenic activity of hESC-CECs.

  13. Morphogen-related therapeutic targets for liver fibrosis

    PubMed Central

    Fung, Eileen; Tsukamoto, Hidekazu

    2015-01-01

    Recent research on hepatic stellate cells (HSCs) has spotlighted the involvement of morphogens in their cell fate determination in liver fibrosis. Temporally and spatially expressed during embryonic development, morphogens are involved in regulation of cell proliferation and differentiation, and tissue patterning. In normal adult liver, morphogens are generally expressed at low levels. However, in liver disease, myofibroblastic HSCs express morphogens such as Wnt, Shh, Necdin, DLK1, and Notch as part of their participation in fibrogenesis and wound healing. Liver regeneration involves cell proliferation and differentiation akin to embryonic liver development where the cells appear to undergo similar fates, and not surprisingly the morphogens are re-activated for the regenerative purpose in adult liver injury. Evidence also points to crosstalk of these morphogens in regulation of HSC fate determination. Genetic ablation or pharmacologic inhibition of morphogens reverts activated HSC to quiescent cells in culture and attenuates progression of hepatic fibrosis. However, positive regulation of liver regeneration by the morphogens needs to be spared. Therapeutically, manipulation of morphogen activities in a cell type and phase-specific manner, should offer new modalities for chronic liver disease. PMID:26206577

  14. Optogenetic Control of Nodal Signaling Reveals a Temporal Pattern of Nodal Signaling Regulating Cell Fate Specification during Gastrulation.

    PubMed

    Sako, Keisuke; Pradhan, Saurabh J; Barone, Vanessa; Inglés-Prieto, Álvaro; Müller, Patrick; Ruprecht, Verena; Čapek, Daniel; Galande, Sanjeev; Janovjak, Harald; Heisenberg, Carl-Philipp

    2016-07-19

    During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation. PMID:27396324

  15. Interpretation of the FGF8 morphogen gradient is regulated by endocytic trafficking.

    PubMed

    Nowak, Matthias; Machate, Anja; Yu, Shuizi Rachel; Gupta, Mansi; Brand, Michael

    2011-02-01

    Forty years ago, it was proposed that during embryonic development and organogenesis, morphogen gradients provide positional information to the individual cells within a tissue leading to specific fate decisions. Recently, much insight has been gained into how such morphogen gradients are formed and maintained; however, which cellular mechanisms govern their interpretation within target tissues remains debated. Here we used in vivo fluorescence correlation spectroscopy and automated image analysis to assess the role of endocytic sorting dynamics on fibroblast growth factor 8 (Fgf8) morphogen gradient interpretation. By interfering with the function of the ubiquitin ligase Cbl, we found an expanded range of Fgf target gene expression and a delay of Fgf8 lysosomal transport. However, the extracellular Fgf8 morphogen gradient remained unchanged, indicating that the observed signalling changes are due to altered gradient interpretation. We propose that regulation of morphogen signalling activity through endocytic sorting allows fast feedback-induced changes in gradient interpretation during the establishment of complex patterns.

  16. Dynamics and precision in retinoic acid morphogen gradients

    PubMed Central

    Schilling, Thomas F.; Nie, Qing; Lander, Arthur D.

    2013-01-01

    Summary Retinoic acid (RA) regulates many cellular behaviors during embryonic development and adult homeostasis. Like other morphogens, RA forms gradients through the use of localized sources and sinks, feedback, and interactions with other signals; this has been particularly well studied in the context of hindbrain segmentation in vertebrate embryos. Yet, as a small lipophilic molecule derived from a dietary source—vitamin A—RA differs markedly from better-studied polypeptide morphogens in its mechanisms of transport, signaling, and removal. Computational models suggest that the distinctive features of RA gradients make them particularly robust to large perturbations. Such features include combined positive and negative feedback effects via intracellular fatty acid binding proteins and RA-degrading enzymes. Here, we discuss how these features, together with feedback interactions among RA target genes, help enable RA to specify multiple, accurate pattern elements in the developing hindbrain, despite operating in an environment of high cellular and biochemical uncertainty and noise. PMID:23266215

  17. Keeping a lid on nodal: transcriptional and translational repression of nodal signalling

    PubMed Central

    Robertson, Elizabeth J.

    2016-01-01

    Nodal is an evolutionarily conserved member of the transforming growth factor-β (TGF-β) superfamily of secreted signalling factors. Nodal factors are known to play key roles in embryonic development and asymmetry in a variety of organisms ranging from hydra and sea urchins to fish, mice and humans. In addition to embryonic patterning, Nodal signalling is required for maintenance of human embryonic stem cell pluripotency and mis-regulated Nodal signalling has been found associated with tumour metastases. Therefore, precise and timely regulation of this pathway is essential. Here, we discuss recent evidence from sea urchins, frogs, fish, mice and humans that show a role for transcriptional and translational repression of Nodal signalling during early development. PMID:26791244

  18. Multiple roles of Activin/Nodal, bone morphogenetic protein, fibroblast growth factor and Wnt/β-catenin signalling in the anterior neural patterning of adherent human embryonic stem cell cultures

    PubMed Central

    Lupo, Giuseppe; Novorol, Claire; Smith, Joseph R.; Vallier, Ludovic; Miranda, Elena; Alexander, Morgan; Biagioni, Stefano; Pedersen, Roger A.; Harris, William A.

    2013-01-01

    Several studies have successfully produced a variety of neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in neural induction, anteroposterior patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective neural induction, but these two pathways have distinct outcomes on rostrocaudal patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during neural induction and promotes acquisition of neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling neural patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification. PMID:23576785

  19. Multiple roles of Activin/Nodal, bone morphogenetic protein, fibroblast growth factor and Wnt/β-catenin signalling in the anterior neural patterning of adherent human embryonic stem cell cultures.

    PubMed

    Lupo, Giuseppe; Novorol, Claire; Smith, Joseph R; Vallier, Ludovic; Miranda, Elena; Alexander, Morgan; Biagioni, Stefano; Pedersen, Roger A; Harris, William A

    2013-04-01

    Several studies have successfully produced a variety of neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in neural induction, anteroposterior patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective neural induction, but these two pathways have distinct outcomes on rostrocaudal patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during neural induction and promotes acquisition of neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling neural patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification. PMID:23576785

  20. Positive modulator of bone morphogenic protein-2

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2009-01-27

    Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

  1. Activin/Nodal signaling and NANOG orchestrate human embryonic stem cell fate decisions by controlling the H3K4me3 chromatin mark

    PubMed Central

    Bertero, Alessandro; Madrigal, Pedro; Galli, Antonella; Hubner, Nina C.; Moreno, Inmaculada; Burks, Deborah; Brown, Stephanie; Pedersen, Roger A.; Gaffney, Daniel; Mendjan, Sasha; Pauklin, Siim

    2015-01-01

    Stem cells can self-renew and differentiate into multiple cell types. These characteristics are maintained by the combination of specific signaling pathways and transcription factors that cooperate to establish a unique epigenetic state. Despite the broad interest of these mechanisms, the precise molecular controls by which extracellular signals organize epigenetic marks to confer multipotency remain to be uncovered. Here, we use human embryonic stem cells (hESCs) to show that the Activin–SMAD2/3 signaling pathway cooperates with the core pluripotency factor NANOG to recruit the DPY30-COMPASS histone modifiers onto key developmental genes. Functional studies demonstrate the importance of these interactions for correct histone 3 Lys4 trimethylation and also self-renewal and differentiation. Finally, genetic studies in mice show that Dpy30 is also necessary to maintain pluripotency in the pregastrulation embryo, thereby confirming the existence of similar regulations in vivo during early embryonic development. Our results reveal the mechanisms by which extracellular factors coordinate chromatin status and cell fate decisions in hESCs. PMID:25805847

  2. An essential role for maternal control of Nodal signaling

    PubMed Central

    Kumari, Pooja; Gilligan, Patrick C; Lim, Shimin; Tran, Long Duc; Winkler, Sylke; Philp, Robin; Sampath, Karuna

    2013-01-01

    Growth factor signaling is essential for pattern formation, growth, differentiation, and maintenance of stem cell pluripotency. Nodal-related signaling factors are required for axis formation and germ layer specification from sea urchins to mammals. Maternal transcripts of the zebrafish Nodal factor, Squint (Sqt), are localized to future embryonic dorsal. The mechanisms by which maternal sqt/nodal RNA is localized and regulated have been unclear. Here, we show that maternal control of Nodal signaling via the conserved Y box-binding protein 1 (Ybx1) is essential. We identified Ybx1 via a proteomic screen. Ybx1 recognizes the 3’ untranslated region (UTR) of sqt RNA and prevents premature translation and Sqt/Nodal signaling. Maternal-effect mutations in zebrafish ybx1 lead to deregulated Nodal signaling, gastrulation failure, and embryonic lethality. Implanted Nodal-coated beads phenocopy ybx1 mutant defects. Thus, Ybx1 prevents ectopic Nodal activity, revealing a new paradigm in the regulation of Nodal signaling, which is likely to be conserved. DOI: http://dx.doi.org/10.7554/eLife.00683.001 PMID:24040511

  3. KEK NODAL system

    SciTech Connect

    Kurokawa, S.; Abe, K.; Akiyama, A.; Katoh, T.; Kikutani, E.; Koiso, H.; Kurihara, N.; Oide, K.; Shinomoto, M.

    1985-10-01

    The KEK NODAL system, which is based on the NODAL devised at the CERN SPS, works on an optical-fiber token ring network of twenty-four minicomputers (Hitachi HIDIC 80's) to control the TRISTAN accelerator complex, now being constructed at KEK. KEK NODAL retains main features of the original NODAL: the interpreting scheme, the multi-computer programming facility, and the data-module concept. In addition, it has the following characteristics: fast execution due to the compiler-interpreter method, a multicomputer file system, a full-screen editing facility, and a dynamic linkage scheme of data modules and NODAL functions. The structure of the KEK NODAL system under PMS, a real-time multitasking operating system of HIDIC 80, is described; the NODAL file system is also explained.

  4. Studies of morphogens: keep calm and carry on

    PubMed Central

    Stathopoulos, Angelike; Iber, Dagmar

    2013-01-01

    Morphogens are signaling factors that direct cell fate and tissue development at a distance from their source, and various modes of transport and interpretation have been suggested for morphogens. The recent EMBO Workshop on ‘Morphogen gradients’, which took place in Oxford, UK in June 2013, centered on the formation and interpretation of such morphogen gradients during development. This meeting allowed an exchange of views in light of recent results. Here, we provide a brief overview of the talks, organized in relation to several major themes of discussion at the meeting: (1) morphogen gradient formation; (2) morphogen gradient interpretation; (3) signaling networks and feedback in morphogenesis; (4) emergence of patterns; (5) scaling of patterns; (6) the control of growth; and (7) new techniques in the field. PMID:24086076

  5. Multi-lineage MSC Differentiation via Engineered Morphogen Fields

    PubMed Central

    Arany, P.R.; Huang, G.X.; Gadish, O.; Feliz, J.; Weaver, J.C.; Kim, J.; Yuen, W.W.; Mooney, D.J.

    2014-01-01

    Tissue loss due to oral diseases requires the healing and regeneration of tissues of multiple lineages. While stem cells are native to oral tissues, a current major limitation to regeneration is the ability to direct their lineage-specific differentiation. This work utilizes polymeric scaffold systems with spatiotemporally controlled morphogen cues to develop precise morphogen fields to direct mesenchymal stem cell differentiation. First, a simple three-layer scaffold design was developed that presented two spatially segregated, lineage-specific cues (Dentinogenic TGF-β1 and Osteogenic BMP4). However, this system resulted in diffuse morphogen fields, as assessed by the in vitro imaging of cell-signaling pathways triggered by the morphogens. Mathematical modeling was then exploited, in combination with incorporation of specific inhibitors (neutralizing antibodies or a small molecule kinase inhibitor) into each morphogen in an opposing spatial pattern as the respective morphogen, to design a five-layer scaffold that was predicted to yield distinct, spatially segregated zones of morphogen signaling. To validate this system, undifferentiated MSCs were uniformly seeded in these scaffold systems, and distinct mineralized tissue differentiation were noted within these morphogen zones. Finally, to demonstrate temporal control over morphogen signaling, latent TGF-β1 was incorporated into one region of a concentric scaffold design, and laser treatment was used to activate the morphogen on-demand and to induce dentin differentiation solely within that specific spatial zone. This study demonstrates a significant advance in scaffold design to generate precise morphogen fields that can be used to develop in situ models to explore tissue differentiation and may ultimately be useful in engineering multi-lineage tissues in clinical dentistry. PMID:25143513

  6. Understanding morphogen gradients: a problem of dispersion and containment.

    PubMed

    Kornberg, Thomas B; Guha, Arjun

    2007-08-01

    Protein morphogens are instructive signals that regulate growth and patterning of tissues and organs. They form long-range, dynamic gradients by moving from regions of high concentration (producing cells) to regions of low concentration (the adjacent, nonproducing developmental field). Since morphogen activity must be limited to the adjacent target field, we want to understand both how signaling proteins move and how their dispersion is restricted. We consider the variety of settings for long-range morphogen systems in Drosophila. In the early embryo, morphogens appear to disperse by free diffusion, and impermeable membranes physically constrain them. However, at later stages, containment is achieved without physical barriers. We argue that in the absence of constraining barriers, gradient-generating dispersion of morphogens cannot be achieved by passive diffusion and that other mechanisms for distribution must be considered.

  7. Nodal-mediated epigenesis requires dynamin-mediated endocytosis

    PubMed Central

    Ertl, Robin P.; Robertson, Anthony J.; Saunders, Diane; Coffman, James A.

    2011-01-01

    Nodal proteins are diffusible morphogens that drive pattern formation via short-range feedback activation coupled to long-range Lefty-mediated inhibition. In the sea urchin embryo, specification of the secondary (oral-aboral) axis occurs via zygotic expression of nodal, which is localized to the prospective oral ectoderm at early blastula stage. In mid-blastula stage embryos treated with low micromolar nickel or zinc, nodal expression expands progressively beyond the confines of this localized domain to encompass the entire equatorial circumference of the embryo, producing radialized embryos lacking an oral-aboral axis. RNAseq analysis of embryos treated with nickel, zinc or cadmium (which does not radialize embryos) showed that several genes involved in endocytosis were similarly perturbed by nickel and zinc but not cadmium. Inhibiting dynamin, a GTPase required for receptor-mediated endocytosis, phenocopies the effects of nickel and zinc, suggesting that dynamin-mediated endocytosis is required as a sink to limit the range of Nodal signaling. PMID:21337468

  8. Spatiotemporal Analysis of Different Mechanisms for Interpreting Morphogen Gradients

    PubMed Central

    Richards, David M.; Saunders, Timothy E.

    2015-01-01

    During development, multicellular organisms must accurately control both temporal and spatial aspects of tissue patterning. This is often achieved using morphogens, signaling molecules that form spatially varying concentrations and so encode positional information. Typical analysis of morphogens assumes that spatial information is decoded in steady state by measuring the value of the morphogen concentration. However, recent experimental work suggests that both pre-steady-state readout and measurement of spatial and temporal derivatives of the morphogen concentration can play important roles in defining boundaries. Here, we undertake a detailed theoretical and numerical study of the accuracy of patterning—both in space and time—in models where readout is provided not by the morphogen concentration but by its spatial and temporal derivatives. In both cases we find that accurate patterning can be achieved, with sometimes even smaller errors than directly reading the morphogen concentration. We further demonstrate that such models provide other potential benefits to the system, such as the ability to switch on and off gene response with a high degree of spatiotemporal accuracy. Finally, we discuss how such derivatives might be calculated biologically and examine these models in relation to Sonic Hedgehog signaling in the vertebrate central nervous system. We show that, when coupled to a downstream transcriptional network, pre-steady-state measurement of the temporal change in the Shh morphogen is a plausible mechanism for determining precise gene boundaries in both space and time. PMID:25902445

  9. Morphogenic Peptides in Regeneration of Load Bearing Tissues.

    PubMed

    Moeinzadeh, Seyedsina; Jabbari, Esmaiel

    2015-01-01

    Morphogenic proteins due to their short half-life require high doses of growth factors in regeneration of load bearing tissues which leads to undesirable side effects. These side effects include bone overgrowth, tumor formation and immune reaction. An alternative approach to reduce undesirable side effects of proteins in regenerative medicine is to use morphogenic peptides derived from the active domains of morphogenic proteins or soluble and insoluble components of the extracellular matrix of mineralized load bearing tissues to induce differentiation of progenitor cells, mineralization, maturation and bone formation. In that regard, many peptides with osteogenic activity have been discovered. These include peptides derived from bone morphogenic proteins (BMPs), those based on interaction with integrin and heparin-binding receptors, collagen derived peptides, peptides derived from other soluble ECM proteins such as bone sialoprotein and enamel matrix proteins, and those peptides derived from vasculoinductive and neuro-inductive proteins. Although these peptides show significant osteogenic activity in vitro and increase mineralization and bone formation in animal models, they are not widely used in clinical orthopedic applications as an alternative to morphogenic proteins. This is partly due to the limited availability of data on structure and function of morphogenic peptides in physiological medium, particularly in tissue engineered scaffolds. Due to their amphiphilic nature, peptides spontaneously self-assemble and aggregate into micellar structures in physiological medium. Aggregation alters the sequence of amino acids in morphogenic peptides that interact with cell surface receptors thus affecting osteogenic activity of the peptide. Aggregation and micelle formation can dramatically reduce the active concentration of morphogenic peptides with many-fold increase in peptide concentration in physiological medium. Other factors that affect bioactivity are the non

  10. Designer Nodal/BMP2 Chimeras Mimic Nodal Signaling, Promote Chondrogenesis, and Reveal a BMP2-like Structure

    PubMed Central

    Esquivies, Luis; Blackler, Alissa; Peran, Macarena; Rodriguez-Esteban, Concepcion; Izpisua Belmonte, Juan Carlos; Booker, Evan; Gray, Peter C.; Ahn, Chihoon; Kwiatkowski, Witek; Choe, Senyon

    2014-01-01

    Nodal, a member of the TGF-β superfamily, plays an important role in vertebrate and invertebrate early development. The biochemical study of Nodal and its signaling pathway has been a challenge, mainly because of difficulties in producing the protein in sufficient quantities. We have developed a library of stable, chemically refoldable Nodal/BMP2 chimeric ligands (NB2 library). Three chimeras, named NB250, NB260, and NB264, show Nodal-like signaling properties including dependence on the co-receptor Cripto and activation of the Smad2 pathway. NB250, like Nodal, alters heart looping during the establishment of embryonic left-right asymmetry, and both NB250 and NB260, as well as Nodal, induce chondrogenic differentiation of human adipose-derived stem cells. This Nodal-induced differentiation is shown to be more efficient than BPM2-induced differentiation. Interestingly, the crystal structure of NB250 shows a backbone scaffold similar to that of BMP2. Our results show that these chimeric ligands may have therapeutic implications in cartilage injuries. PMID:24311780

  11. Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells

    PubMed Central

    Mavrakis, Konstantinos J.; Goggolidou, Paraskevi; Norris, Dominic P.; Episkopou, Vasso

    2009-01-01

    The Transforming Growth Factor (TGF) β signalling family includes morphogens, such as Nodal and Activin, with important functions in vertebrate development. The concentration of the morphogen is critical for fate decisions in the responding cells. Smad2 and Smad3 are effectors of the Nodal/Activin branch of TGFβ signalling: they are activated by receptors, enter the nucleus and directly transcribe target genes. However, there have been no studies correlating levels of Smad2/3 activation with expression patterns of endogenous target genes in a developmental context over time. We used mouse Embryonic Stem (ES) cells to create a system whereby levels of activated Smad2/3 can be manipulated by an inducible constitutively active receptor (Alk4*) and an inhibitor (SB-431542) that blocks specifically Smad2/3 activation. The transcriptional responses were analysed by microarrays at different time points during activation and repression. We identified several genes that follow faithfully and reproducibly the Smad2/3 activation profile. Twenty-seven of these were novel and expressed in the early embryo downstream of Smad2/3 signalling. As they responded to Smad2/3 activation in the absence of protein synthesis, they were considered direct. These immediate responsive genes included negative intracellular feedback factors, like SnoN and I-Smad7, which inhibit the transcriptional activity of Smad2/3. However, their activation did not lead to subsequent repression of target genes over time, suggesting that this type of feedback is inefficient in ES cells or it is counteracted by mechanisms such as ubiquitin-mediated degradation by Arkadia. Here we present an ES cell system along with a database containing the expression profile of thousands of genes downstream of Smad2/3 activation patterns, in the presence or absence of protein synthesis. Furthermore, we identify primary target genes that follow proportionately and with high sensitivity changes in Smad2/3 levels over 15–30

  12. Nodal-chain metals

    NASA Astrophysics Data System (ADS)

    Bzdušek, Tomáš; Wu, Quansheng; Rüegg, Andreas; Sigrist, Manfred; Soluyanov, Alexey A.

    2016-10-01

    The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain—a chain of connected loops in momentum space—along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF4), as well as in other compounds of this class of materials. Using IrF4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.

  13. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    SciTech Connect

    Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-04-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE{sup -/-}) versus wild type (AChE{sup +/+}) mice indicated that while these OPs inhibited axonal growth in AChE{sup +/+} DRG neurons, they had no effect on axonal growth in AChE{sup -/-} DRG neurons. However, transfection of AChE{sup -/-} DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.

  14. Chlorpyrifos and Chlorpyrifos-Oxon Inhibit Axonal Growth by Interfering with the Morphogenic Activity of Acetylcholinesterase

    PubMed Central

    Yang, Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-01-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE−/−) versus wildtype (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE−/− DRG neurons. However, transfection of AChE−/− DRG neurons with cDNA encoding full-length AChE restored the wildtype response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs. PMID:18076960

  15. Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds.

    PubMed

    Sakata, Ryosuke; Iwakura, Takashi; Reddi, A Hari

    2015-10-01

    The articular cartilage is a well-organized tissue for smooth and friction-free joint movement for locomotion in animals and humans. Adult articular cartilage has a very low self-regeneration capacity due to its avascular nature. The regeneration of articular cartilage surface is critical to prevent the progression to osteoarthritis (OA). Although various joint resurfacing procedures in experimental articular cartilage defects have been developed, no standardized clinical protocol has yet been established. The three critical ingredients for tissue regeneration are morphogens and growth factors, cells, and scaffolds. The concepts based on the regeneration triad have been extensively investigated in animal models. However, these studies in animal models have demonstrated variable results and outcomes. An optimal animal model must precisely mimic and model the sequence of events in articular cartilage regeneration in human. In this article, the progress and remaining challenges in articular cartilage regeneration in animal models are reviewed. The role of individual morphogens and growth factors in cartilage regeneration has been investigated. In normal articular cartilage homeostasis, morphogens and growth factors function sequentially in tissue regeneration. Mesenchymal stem cell-based repair of articular cartilage defects, performed with or without various growth factors and scaffolds, has been widely attempted in animal models. Stem cells, including embryonic and adult stem cells and induced pluripotent stem cells, have also been reported as attractive cell sources for articular cartilage surface regeneration. Several studies with regard to scaffolds have been advanced, including recent investigations based on nanomaterials, functional mechanocompatible scaffolds, multilayered scaffolds, and extracellular matrix scaffolds for articular cartilage surface regeneration. Continuous refinement of animal models in chondral and osteochondral defects provide opportunities

  16. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    PubMed

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth.

  17. Nonlinear degradation-enhanced transport of morphogens performing subdiffusion.

    PubMed

    Fedotov, Sergei; Falconer, Steven

    2014-01-01

    We study a morphogen gradient formation under nonlinear degradation and subdiffusive transport. In the long-time limit, we obtain the nonlinear effect of degradation-enhanced diffusion, resulting from the interaction of non-Markovian subdiffusive transport with a nonlinear reaction. We find the stationary profile of power-law type, which has implications for robustness, with the shape of the profile being controlled by the anomalous exponent. Far away from the source of morphogens, any changes in the rate of production are not felt.

  18. ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm.

    PubMed

    Ellis, Pamela S; Burbridge, Sarah; Soubes, Sandrine; Ohyama, Kyoji; Ben-Haim, Nadav; Chen, Canhe; Dale, Kim; Shen, Michael M; Constam, Daniel; Placzek, Marysia

    2015-11-15

    The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we show that in the embryonic chick, Shh is expressed transiently in prechordal mesoderm, and is governed by unprocessed Nodal. Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained through canonical signalling, Nodal signals through a non-canonical route to maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co-immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression. Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3 siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA to prechordal mesoderm in vivo results in premature Shh downregulation without affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3 signalling is downregulated.

  19. ProNodal acts via FGFR3 to govern duration of Shh expression in the prechordal mesoderm

    PubMed Central

    Ellis, Pamela S.; Burbridge, Sarah; Soubes, Sandrine; Ohyama, Kyoji; Ben-Haim, Nadav; Chen, Canhe; Dale, Kim; Shen, Michael M.; Constam, Daniel; Placzek, Marysia

    2015-01-01

    The secreted glycoprotein sonic hedgehog (Shh) is expressed in the prechordal mesoderm, where it plays a crucial role in induction and patterning of the ventral forebrain. Currently little is known about how Shh is regulated in prechordal tissue. Here we show that in the embryonic chick, Shh is expressed transiently in prechordal mesoderm, and is governed by unprocessed Nodal. Exposure of prechordal mesoderm microcultures to Nodal-conditioned medium, the Nodal inhibitor CerS, or to an ALK4/5/7 inhibitor reveals that Nodal is required to maintain both Shh and Gsc expression, but whereas Gsc is largely maintained through canonical signalling, Nodal signals through a non-canonical route to maintain Shh. Further, Shh expression can be maintained by a recombinant Nodal cleavage mutant, proNodal, but not by purified mature Nodal. A number of lines of evidence suggest that proNodal acts via FGFR3. ProNodal and FGFR3 co-immunoprecipitate and proNodal increases FGFR3 tyrosine phosphorylation. In microcultures, soluble FGFR3 abolishes Shh without affecting Gsc expression. Further, prechordal mesoderm cells in which Fgfr3 expression is reduced by Fgfr3 siRNA fail to bind to proNodal. Finally, targeted electroporation of Fgfr3 siRNA to prechordal mesoderm in vivo results in premature Shh downregulation without affecting Gsc. We report an inverse correlation between proNodal-FGFR3 signalling and pSmad1/5/8, and show that proNodal-FGFR3 signalling antagonises BMP-mediated pSmad1/5/8 signalling, which is poised to downregulate Shh. Our studies suggest that proNodal/FGFR3 signalling governs Shh duration by repressing canonical BMP signalling, and that local BMPs rapidly silence Shh once endogenous Nodal-FGFR3 signalling is downregulated. PMID:26417042

  20. Development of morphogen gradient: The role of dimension and discreteness

    SciTech Connect

    Teimouri, Hamid; Kolomeisky, Anatoly B.

    2014-02-28

    The fundamental processes of biological development are governed by multiple signaling molecules that create non-uniform concentration profiles known as morphogen gradients. It is widely believed that the establishment of morphogen gradients is a result of complex processes that involve diffusion and degradation of locally produced signaling molecules. We developed a multi-dimensional discrete-state stochastic approach for investigating the corresponding reaction-diffusion models. It provided a full analytical description for stationary profiles and for important dynamic properties such as local accumulation times, variances, and mean first-passage times. The role of discreteness in developing of morphogen gradients is analyzed by comparing with available continuum descriptions. It is found that the continuum models prediction about multiple time scales near the source region in two-dimensional and three-dimensional systems is not supported in our analysis. Using ideas that view the degradation process as an effective potential, the effect of dimensionality on establishment of morphogen gradients is also discussed. In addition, we investigated how these reaction-diffusion processes are modified with changing the size of the source region.

  1. Morphogengineering roots: comparing mechanisms of morphogen gradient formation

    PubMed Central

    2012-01-01

    Background In developmental biology, there has been a recent focus on the robustness of morphogen gradients as possible providers of positional information. It was shown that functional morphogen gradients present strong biophysical constraints and lack of robustness to noise. Here we explore how the details of the mechanism which underlies the generation of a morphogen gradient can influence those properties. Results We contrast three gradient-generating mechanisms, (i) a source-decay mechanism; and (ii) a unidirectional transport mechanism; and (iii) a so-called reflux-loop mechanism. Focusing on the dynamics of the phytohormone auxin in the root, we show that only the reflux-loop mechanism can generate a gradient that would be adequate to supply functional positional information for the Arabidopsis root, for biophysically reasonable kinetic parameters. Conclusions We argue that traits that differ in spatial and temporal time-scales can impose complex selective pressures on the mechanism of morphogen gradient formation used for the development of the particular organism. PMID:22583698

  2. Morphogenic machines evolve more rapidly than the signals that pattern them: lessons from amphibians.

    PubMed

    Shook, David R; Keller, Ray

    2008-01-15

    The induction of mesoderm and the patterning of its dorsal-ventral and anterior-posterior axes seems to be relatively conserved throughout the chordates, as do the morphogenic movements that produce a phylotypic stage embryo. What is not conserved is the initial embryonic architecture of the fertilized egg, and the specific cell behaviors used to drive mesoderm morphogenesis. How then do conserved patterning pathways adapt to diverse architectures and where do they diverge to direct the different cell behaviors used to shape the phylotypic body plan? Amphibians in particular, probably because of their broad range of reproductive strategies, show diverse embryonic architectures across their class and use diverse cell behaviors during their early morphogenesis, making them an interesting comparative group. We examine three examples from our work on amphibians that show variations in the use of cell behaviors to drive the morphogenesis of the same tissues. We also consider possible points where the conserved patterning pathways might diverge to produce different cell behaviors.

  3. Nodal promotes invasive phenotypes via a Mitogen Activated Protein Kinase-dependent pathway

    PubMed Central

    Quail, DF; Zhang, G; Findlay, SD; Hess, DA; Postovit, LM

    2016-01-01

    The progression of cancer from localized to invasive disease is requisite for metastasis, and is often characterized by epithelial-to-mesenchymal transition (EMT) and alterations in cellular adhesion and migration. Studies have shown that this transition is associated with an up-regulation of embryonic stem cell-associated genes, resulting in a dedifferentiated phenotype and poor patient prognosis. Nodal is an embryonic factor that plays a critical role in promoting early invasive events during development. Nodal is silenced as stem cells differentiate; however, it re-emerges in adult life during placentation and mammary gland development, and is aberrantly expressed in many cancers. Here, we show that Nodal over-expression, in poorly-invasive breast cancer and choriocarcinoma cells, causes increased invasion and migration in vitro. Furthermore, we show that Nodal over-expression in these epithelial cancer types induces an EMT-like event concomitant with the internalization of E-Cadherin. This ability of Nodal to promote cellular invasion and EMT-like phenomena is dependent upon the phosphorylation of ERK1/2. Since Nodal normally signals through SMADs, these findings lend insight into an alternative pathway that is hijacked by this protein in cancer. To evaluate the clinical implications of our results, we show that Nodal inhibition reduces liver tumor burden in a model of spontaneous breast cancer metastasis in vivo, and that Nodal loss-of-function in aggressive breast cancer lines results in a decrease in invasive phenotypes. Our results demonstrate that Nodal is involved in promoting invasion in multiple cellular contexts, and that Nodal inhibition may be useful as a therapeutic target for patients with progressive disease. PMID:23334323

  4. Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development.

    PubMed Central

    Bigbee, J W; Sharma, K V; Gupta, J J; Dupree, J L

    1999-01-01

    Acetylcholinesterase (AChE) is the enzyme that hydrolyzes the neurotransmitter acetylcholine at cholinergic synapses and neuromuscular junctions. However, results from our laboratory and others indicate that AChE has an extrasynaptic, noncholinergic role during neural development. This article is a review of our findings demonstrating the morphogenic role of AChE, using a neuronal cell culture model. We also discuss how these data suggest that AChE has a cell adhesive function during neural development. These results could have additional significance as AChE is the target enzyme of agricultural organophosphate and carbamate pesticides as well as the commonly used household organophosphate chlorpyrifos (Dursban). Prenatal exposure to these agents could have adverse effects on neural development by interfering with the morphogenic function of AChE. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:10229710

  5. Planar Polarity: Converting a Morphogen Gradient into Cellular Polarity

    PubMed Central

    Collu, Giovanna M.; Mlodzik, Marek

    2015-01-01

    Epithelial cells are polarized within the apico-basal and planar axes. The latter—planar cell polarity—requires long-range regulation of orientation as well as short-range, cell-to-cell realignment through feedback loops. New insights into the long-range, gradient-type regulation reveal how a kinase translates the morphogen gradient input into cellular orientation. PMID:25942551

  6. Activin/Nodal signalling before implantation: setting the stage for embryo patterning

    PubMed Central

    Papanayotou, Costis; Collignon, Jérôme

    2014-01-01

    Activins and Nodal are members of the transforming growth factor beta (TGF-β) family of growth factors. Their Smad2/3-dependent signalling pathway is well known for its implication in the patterning of the embryo after implantation. Although this pathway is active early on at preimplantation stages, embryonic phenotypes for loss-of-function mutations of prominent components of the pathway are not detected before implantation. It is only fairly recently that an understanding of the role of the Activin/Nodal signalling pathway at these stages has started to emerge, notably from studies detailing how it controls the expression of target genes in embryonic stem cells. We review here what is currently known of the TGF-β-related ligands that determine the activity of Activin/Nodal signalling at preimplantation stages, and recent advances in the elucidation of the Smad2/3-dependent mechanisms underlying developmental progression. PMID:25349448

  7. Activin/Nodal signalling before implantation: setting the stage for embryo patterning.

    PubMed

    Papanayotou, Costis; Collignon, Jérôme

    2014-12-01

    Activins and Nodal are members of the transforming growth factor beta (TGF-β) family of growth factors. Their Smad2/3-dependent signalling pathway is well known for its implication in the patterning of the embryo after implantation. Although this pathway is active early on at preimplantation stages, embryonic phenotypes for loss-of-function mutations of prominent components of the pathway are not detected before implantation. It is only fairly recently that an understanding of the role of the Activin/Nodal signalling pathway at these stages has started to emerge, notably from studies detailing how it controls the expression of target genes in embryonic stem cells. We review here what is currently known of the TGF-β-related ligands that determine the activity of Activin/Nodal signalling at preimplantation stages, and recent advances in the elucidation of the Smad2/3-dependent mechanisms underlying developmental progression.

  8. Complement components C1r/C1s, bone morphogenic protein 1 and Xenopus laevis developmentally regulated protein UVS.2 share common repeats.

    PubMed

    Bork, P

    1991-04-22

    Property patterns were constructed, based on an alignment of related domains in human complement subcomponents C1r and C1s as well as in the sea urchin protein uEGF. This kind of consensus pattern was able to identify similar domains in a human bone morphogenic protein, in a Xenopus laevis embryonal protein involved in dorsoanterior development and in a calcium-dependent serine protease secreted from malignant hamster embryo fibroblast cells. Because of the high level of overall sequence homology this protease may be the hamsters' equivalent of the human complement subcomponent C1s. The resulting multiple alignment of all studied domains suggests functionally and structurally important regions.

  9. Sizn1 is a novel protein that functions as a transcriptional coactivator of bone morphogenic protein signaling.

    PubMed

    Cho, Ginam; Lim, Youngshin; Zand, Dina; Golden, Jeffrey A

    2008-03-01

    Bone morphogenic proteins (BMPs) play pleotrophic roles in nervous system development, and their signaling is highly regulated at virtually every step in the pathway. We have cloned a novel gene, Sizn1 (Smad-interacting zinc finger protein), which functions as a transcriptional coactivator of BMP signaling. It positively modulates BMP signaling by interacting with Smad family members and associating with CBP in the transcription complex. Sizn1 is expressed in the ventral embryonic forebrain, where, as we will show, it contributes to BMP-dependent, cholinergic-neuron-specific gene expression. These data indicate that Sizn1 is a positive modulator of BMP signaling and provide further insight into how BMP signaling can be modulated in neuronal progenitor subsets to influence cell-type-specific gene expression and development.

  10. Nicalin and its binding partner Nomo are novel Nodal signaling antagonists.

    PubMed

    Haffner, Christof; Frauli, Mélanie; Topp, Stephanie; Irmler, Martin; Hofmann, Kay; Regula, Jörg T; Bally-Cuif, Laure; Haass, Christian

    2004-08-01

    Nodals are signaling factors of the transforming growth factor-beta (TGFbeta) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish. PMID:15257293

  11. Quantifying stretch and secretion in the embryonic lung: Implications for morphogenesis☆

    PubMed Central

    George, Uduak Z.; Bokka, Kishore K.; Warburton, David; Lubkin, Sharon R.

    2016-01-01

    Branching in the embryonic lung is controlled by a variety of morphogens. Mechanics is also believed to play a significant role in lung branching. The relative roles and interactions of these two broad factors are challenging to determine. We considered three hypotheses for explaining why tracheal occlusion triples branching with no overall increase in size. Both hypotheses are based on tracheal occlusion blocking the exit of secretions. (H1) Increased lumen pressure stretches tissues; stretch receptors at shoulders of growing tips increase local rate of branching. (H2) Blocking exit of secretions blocks advective transport of morphogens, leading to (H2a) increased overall concentration of morphogens or (H2b) increased flux of morphogens at specific locations. We constructed and analyzed computational models of tissue stretch and solute transport in a 3D lung geometry. Observed tissue stresses and stretches were predominantly in locations unrelated to subsequent branch locations, suggesting that tissue stretch (H1) is not the mechanism of enhancement of branching. Morphogen concentration in the mesenchyme (H2a) increased with tracheal occlusion, consistent with previously reported results. Morphogen flux at the epithelial surface (H2b) completely changed its distribution pattern when the trachea was occluded, tripling the number of locations at which it was elevated. Our results are consistent with the hypothesis that tracheal occlusion blocks outflow of secretions, leading to a higher number of high-flux locations at branching tips, in turn leading to a large increase in number of branching locations. PMID:26189687

  12. Fluid mechanics of nodal flow due to embryonic primary cilia.

    PubMed

    Smith, D J; Blake, J R; Gaffney, E A

    2008-05-01

    Breaking of left-right symmetry is crucial in vertebrate development. The role of cilia-driven flow has been the subject of many recent publications, but the underlying mechanisms remain controversial. At approximately 8 days post-fertilization, after the establishment of the dorsal-ventral and anterior-posterior axes, a depressed structure is found on the ventral side of mouse embryos, termed the ventral node. Within the node, 'whirling' primary cilia, tilted towards the posterior, drive a flow implicated in the initial left-right signalling asymmetry. However, the underlying fluid mechanics have not been fully and correctly explained until recently and accurate characterization is required in determining how the flow triggers the downstream signalling cascades. Using the approximation of resistive force theory, we show how the flow is produced and calculate the optimal configuration to cause maximum flow, showing excellent agreement with in vitro measurements and numerical simulation, and paralleling recent analogue experiments. By calculating numerical solutions of the slender body theory equations, we present time-dependent physically based fluid dynamics simulations of particle pathlines in flows generated by large arrays of beating cilia, showing the far-field radial streamlines predicted by the theory.

  13. Theoretical analysis of degradation mechanisms in the formation of morphogen gradients

    NASA Astrophysics Data System (ADS)

    Bozorgui, Behnaz; Teimouri, Hamid; Kolomeisky, Anatoly B.

    2015-07-01

    Fundamental biological processes of development of tissues and organs in multicellular organisms are governed by various signaling molecules, which are called morphogens. It is known that spatial and temporal variations in the concentration profiles of signaling molecules, which are frequently referred as morphogen gradients, lead to a cell differentiation via activating specific genes in a concentration-dependent manner. It is widely accepted that the establishment of the morphogen gradients involves multiple biochemical reactions and diffusion processes. One of the critical elements in the formation of morphogen gradients is a degradation of signaling molecules. We develop a new theoretical approach that provides a comprehensive description of the degradation mechanisms. It is based on the idea that the degradation works as an effective potential that drives the signaling molecules away from the source region. Utilizing the method of first-passage processes, the dynamics of the formation of morphogen gradients for various degradation mechanisms is explicitly evaluated. It is found that linear degradation processes lead to a dynamic behavior specified by times to form the morphogen gradients that depend linearly on the distance from the source. This is because the effective potential due to the degradation is quite strong. At the same time, nonlinear degradation mechanisms yield a quadratic scaling in the morphogen gradients formation times since the effective potentials are much weaker. Physical-chemical explanations of these phenomena are presented.

  14. Morphogen-defined patterning of Escherichia coli enabled by an externally tunable band-pass filter

    PubMed Central

    Sohka, Takayuki; Heins, Richard A; Ostermeier, Marc

    2009-01-01

    Background Gradients of morphogens pattern cell fate – a phenomenon that is especially important during development. A simple model system for studying how morphogens pattern cell behavior would overcome difficulties inherent in the study of natural morphogens in vivo. A synthetic biology approach to building such a system is attractive. Results Using an externally-tunable band-pass filter paradigm, we engineered Escherichia coli cells to function as a model system for the study of how multiple morphogens can pattern cell behavior. We demonstrate how our system exhibits behavior such as morphogen crosstalk and how the cells' growth and fluorescence can be patterned in a number of complex patterns. We extend our cell patterning from 2D cultures on the surface of plates to 3D cultures in soft agarose medium. Conclusion Our system offers a convenient, well-defined model system for fundamental studies on how multiple morphogen gradients can affect cell fate and lead to pattern formation. Our design principles could be applied to eukaryotic cells to develop other models systems for studying development or for enabling the patterning of cells for applications such as tissue engineering and biomaterials. PMID:19586541

  15. An atlas of gene regulatory networks reveals multiple three-gene mechanisms for interpreting morphogen gradients

    PubMed Central

    Cotterell, James; Sharpe, James

    2010-01-01

    The interpretation of morphogen gradients is a pivotal concept in developmental biology, and several mechanisms have been proposed to explain how gene regulatory networks (GRNs) achieve concentration-dependent responses. However, the number of different mechanisms that may exist for cells to interpret morphogens, and the importance of design features such as feedback or local cell–cell communication, is unclear. A complete understanding of such systems will require going beyond a case-by-case analysis of real morphogen interpretation mechanisms and mapping out a complete GRN ‘design space.' Here, we generate a first atlas of design space for GRNs capable of patterning a homogeneous field of cells into discrete gene expression domains by interpreting a fixed morphogen gradient. We uncover multiple very distinct mechanisms distributed discretely across the atlas, thereby expanding the repertoire of morphogen interpretation network motifs. Analyzing this diverse collection of mechanisms also allows us to predict that local cell–cell communication will rarely be responsible for the basic dose-dependent response of morphogen interpretation networks. PMID:21045819

  16. Systems control of BMP morphogen flow in vertebrate embryos

    PubMed Central

    Plouhinec, Jean-Louis; Zakin, Lise; De Robertis, Edward M.

    2011-01-01

    Embryonic morphogenetic programs coordinate cell behavior to ensure robust pattern formation. Having identified components of those programs by molecular genetics, developmental biology is now borrowing concepts and tools from systems biology to decode their regulatory logic. Dorsal-ventral (D-V) patterning of the frog gastrula by Bone Morphogenetic Proteins (BMPs) is one of the best studied examples of a self-regulating embryonic patterning system. Embryological analyses and mathematical modeling are revealing that the BMP activity gradient is maintained by a directed flow of BMP ligands towards the ventral side. Pattern robustness is ensured through feedback control of the levels of extracellular BMP pathway modulators that adjust the flow to the dimensions of the embryonic field. PMID:21937218

  17. Bone morphogenic protein-4 expression in vascular lesions of calciphylaxis.

    PubMed

    Griethe, Wanja; Schmitt, Roland; Jurgensen, Jan Steffen; Bachmann, Sebastian; Eckardt, Kai-Uwe; Schindler, Ralf

    2003-01-01

    Calciphylaxis is characterized by an extensive media-calcification of cutaneous and subcutaneous arterioles and capillaries. Recent studies have provided evidence that vascular calcification is a process with similarities to bone metabolism. Bone morphogenic protein-4 (BMP-4) is physiologically involved in bone development and repair. The presence of BMP-4 in atherosclerosis and in sclerotic heart valves led us to suggest that BMP-4 is also involved in calciphylaxis. A 47-year-old male patient developed end-stage renal failure due to chronic glomerulonephritis. He has had two kidney transplants with an immunosuppressive regimen consisting of cyclosporine A and steroids. He was admitted to our hospital because of an increase in serum creatinine (Cr) and he subsequently developed progressive dermal ulcerations. A skin biopsy led to the diagnosis of calciphylaxis. Immunohistochemistry for BMP-4 of a skin specimen from our patient showed strong cytoplasmic immunoreactivity of intradermal cells with clear spatial association to arterioles and hair follicles. Whereas there are identified inhibitors and promoters of vascular calcification, the presence of BMP-4 has not been demonstrated in calcific uremic arteriolopathy. In contrast to atherosclerosis, BMP-4 in calciphylaxis cannot be found in vascular media, but in intradermal cells at the border of arterioles and hair follicles. Therefore, in calciphylaxis BMP-4 can play the role of a cytokine, a growth factor or a media-calcification promoter. PMID:14733421

  18. Effects of Bone Morphogenic Proteins on Engineered Cartilage

    NASA Technical Reports Server (NTRS)

    Gooch, Keith, J.; Blunk, Torsten; Courter, Donald L.; Sieminski, Alisha; Vunjak-Novakovic, Gordana; Freed, Lisa E.

    2007-01-01

    A report describes experiments on the effects of bone morphogenic proteins (BMPs) on engineered cartilage grown in vitro. In the experiments, bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid scaffolds and cultured in, variously, a control medium or a medium supplemented with BMP-2, BMP-12, or BMP-13 in various concentrations. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks macroscopically and histologically resembled native cartilage. At a concentration of 100 ng/mL, BMP-2, BMP-12, or BMP-13 caused (1) total masses of the constructs to exceed those of the controls by 121, 80, or 62 percent, respectively; (2) weight percentages of glycosaminoglycans in the constructs to increase by 27, 18, or 15, respectively; and (3) total collagen contents of the constructs to decrease to 63, 89, or 83 percent of the control values, respectively. BMP-2, but not BMP-12 or BMP-13, promoted chondrocyte hypertrophy. These observations were interpreted as suggesting that the three BMPs increase the growth rates and modulate the compositions of engineered cartilage. It was also concluded that in vitro engineered cartilage is a suitable system for studying effects of BMPs on chondrogenesis in a well-defined environment.

  19. Occult nodal metastasis in solid carcinomata

    SciTech Connect

    Moloy, P.J.; Nicolson, G.L.

    1987-01-01

    This book contains 23 selections. Some of the titles are: Rationale for radiotherapy in subclinical nodal disease; rationale of chemotherapy for nodal disease: The stabilization of topoisomerase II-DNA complexes as a mechanism of antineoplastic drug action; magnetic resonance imaging of malignant cervical adenopathy; and local and regional immune function in cancer patients.

  20. Heterogeneous treatment in the variational nodal method

    SciTech Connect

    Fanning, T.H.; Palmiotti, G.

    1995-06-01

    The variational nodal transport method is reduced to its diffusion form and generalized for the treatment of heterogeneous nodes while maintaining nodal balances. Adapting variational methods to heterogeneous nodes requires the ability to integrate over a node with discontinuous cross sections. In this work, integrals are evaluated using composite gaussian quadrature rules, which permit accurate integration while minimizing computing time. Allowing structure within a nodal solution scheme avoids some of the necessity of cross section homogenization, and more accurately defines the intra-nodal flux shape. Ideally, any desired heterogeneity can be constructed within the node; but in reality, the finite set of basis functions limits the practical resolution to which fine detail can be defined within the node. Preliminary comparison tests show that the heterogeneous variational nodal method provides satisfactory results even if some improvements are needed for very difficult, configurations.

  1. Butterfly wing patterns: how good a determining mechanism is the simple diffusion of a single morphogen?

    PubMed

    Bard, J B; French, V

    1984-12-01

    The formation of the wing pigmentation patterns of three species of butterflies has been modelled using a mechanism based on a tripod of assumptions. First, that there may be morphogen sources in the foci of eyespots and morphogen sinks at some parts of the wing margin, all other cells being passive. Second, that the morphogen has a finite half life and diffuses simply and freely away from the sources throughout a wing of hexagonally packed cells. Third, that the overt pattern derives from cells interpreting the local morphogen concentration with respect to thresholds which determine scale colours. The final pattern thus follows lines of constant morphogen concentration and may, depending on the distribution of sources, comprise rings, curves or bands. With such a model, we have been able to compute stable patterns having the essential topology of the compound spots of Tenaris domitilla, the large rings of Diaethria marchalii and the pattern of eyespots, rings and asymmetric bands of Ragadia minoa. Quantitative analysis of the pattern-forming process shows that, with a biologically realistic diffusion constant (approximately 5.10(-7) cm2 sec-1) and a morphogen half life less than 6h, the patterns form within approximately 12h over a wing of approximately 1000 cells in length. The limitations of the model are that the exact morphology of the eyespots and bands do not match precisely those of the original wings, that there are edge distortions and that optimal patterns may be critically dependent on the exact positions of sources and sinks. An explanation for part of the discrepancy is that we have assumed an adult wing shape and foci coordinates in modelling a process that took place earlier in development. Nevertheless, the limitations of the model argue against a mechanism based on a single morphogen operating in vivo. However, as the model can generate many features of butterfly wing patterns, it may be considered as a degenerate case of that mechanism. PMID

  2. Butterfly wing patterns: how good a determining mechanism is the simple diffusion of a single morphogen?

    PubMed

    Bard, J B; French, V

    1984-12-01

    The formation of the wing pigmentation patterns of three species of butterflies has been modelled using a mechanism based on a tripod of assumptions. First, that there may be morphogen sources in the foci of eyespots and morphogen sinks at some parts of the wing margin, all other cells being passive. Second, that the morphogen has a finite half life and diffuses simply and freely away from the sources throughout a wing of hexagonally packed cells. Third, that the overt pattern derives from cells interpreting the local morphogen concentration with respect to thresholds which determine scale colours. The final pattern thus follows lines of constant morphogen concentration and may, depending on the distribution of sources, comprise rings, curves or bands. With such a model, we have been able to compute stable patterns having the essential topology of the compound spots of Tenaris domitilla, the large rings of Diaethria marchalii and the pattern of eyespots, rings and asymmetric bands of Ragadia minoa. Quantitative analysis of the pattern-forming process shows that, with a biologically realistic diffusion constant (approximately 5.10(-7) cm2 sec-1) and a morphogen half life less than 6h, the patterns form within approximately 12h over a wing of approximately 1000 cells in length. The limitations of the model are that the exact morphology of the eyespots and bands do not match precisely those of the original wings, that there are edge distortions and that optimal patterns may be critically dependent on the exact positions of sources and sinks. An explanation for part of the discrepancy is that we have assumed an adult wing shape and foci coordinates in modelling a process that took place earlier in development. Nevertheless, the limitations of the model argue against a mechanism based on a single morphogen operating in vivo. However, as the model can generate many features of butterfly wing patterns, it may be considered as a degenerate case of that mechanism.

  3. Symmetry Breaking in a Model for Nodal Cilia

    NASA Astrophysics Data System (ADS)

    Brokaw, Charles J.

    2005-03-01

    Nodal cilia are very short cilia found in the embryonic node on the ventral surface of early mammalian embryos. They create a right to left fluid flow that is responsible for determining the normal asymmetry of the internal organs of the mammalian body. To do this, the distal end of the cilium must circle in a counterclockwise sense. Computer simulations with 3-dimensional models of flagella allow examination of 3-dimensional movements such as those of nodal cilia. 3-dimensional circling motions of short cilia can be achieved with velocity controlled models, in which dynein activity is regulated by sliding velocity. If dyneins on one outer doublet are controlled by the sliding velocity experienced by that doublet, the system is symmetric, and the 3-dimensional models can show either clockwise or counterclockwise circling. My computer simulations have examined two possible symmetry breaking mechanisms: 1) dyneins on doublet N are regulated by a mixture of the sliding velocities experienced by doublets N and N+1 (numbered in a clockwise direction, looking from the base). or 2) symmetry is broken by an off-axis force that produces a right-handed twist of the axoneme, consistent with observations that some dyneins can rotate their substrate microtubules in a clockwise direction.

  4. Temporal control of self-organized pattern formation without morphogen gradients in bacteria

    PubMed Central

    Payne, Stephen; Li, Bochong; Cao, Yangxiaolu; Schaeffer, David; Ryser, Marc D; You, Lingchong

    2013-01-01

    Diverse mechanisms have been proposed to explain biological pattern formation. Regardless of their specific molecular interactions, the majority of these mechanisms require morphogen gradients as the spatial cue, which are either predefined or generated as a part of the patterning process. However, using Escherichia coli programmed by a synthetic gene circuit, we demonstrate here the generation of robust, self-organized ring patterns of gene expression in the absence of an apparent morphogen gradient. Instead of being a spatial cue, the morphogen serves as a timing cue to trigger the formation and maintenance of the ring patterns. The timing mechanism enables the system to sense the domain size of the environment and generate patterns that scale accordingly. Our work defines a novel mechanism of pattern formation that has implications for understanding natural developmental processes. PMID:24104480

  5. Visualization of an endogenous retinoic acid gradient across embryonic development.

    PubMed

    Shimozono, Satoshi; Iimura, Tadahiro; Kitaguchi, Tetsuya; Higashijima, Shin-Ichi; Miyawaki, Atsushi

    2013-04-18

    In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and

  6. An ultrastructural study of sinuatrial node cells in the embryonic rat heart.

    PubMed Central

    Domenech-Mateu, J M; Boya-Vegué, J

    1975-01-01

    Sinuatrial nodal tissue, obtained from rat embryos of 15, 16 and 17 days, was examined with the electron microscope. Embryonic nodal cells were generally similar to adult cells except that (1) they showed thick prolongations of the cytoplasm which insinuated themselves between neighbouring cells; (2) they possessed osmiophilic granules with a predeliction for the region of the Golgi complex; (3) they exhibited a lesser and variable degree of pinocytosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:1133091

  7. [The Nodal regulated dusp4 inhibits mesendoderm formation during zebrafish gastrulation].

    PubMed

    Liu, Zhao-Ting; Wei, Shi; Wang, Qiang

    2012-09-01

    MAP kinase phosphatase-2 (MKP-2/DUSP4), a dual specificity protein phosphatase with tyrosine/serine/ threonine phosphatase activity, is associated with cellular proliferation and differentiation, but its functions during embryo development are unclear. To study the developmental function of dusp4, we first examined the spatiotemporal expression pattern of this gene during zebrafish embryonic development by whole mount in situ hybridization. We found that dusp4 was maternally expressed since its transcripts were present from the one-cell to the 256-cell stages. At early gastrulation stages, dusp4 transcripts specifically distributed at margin region, where the mesendodermal cells were located. Further-more, Nodal signal was crucial for dusp4 expression. The expression of dusp4 was obviously increased in Nodal ligand overexpressed embryos, while its expression was almost lost in the Nodal signal-deficient MZoep mutants. In addition, dusp4 MO was also designed to knock down its expression in embryos. The mesendoderm formation was significantly in-creased in dusp4 morphants, but not obviously changed in dusp4 overexpressed embryos, suggesting that dusp4 is necessary, but not sufficient for the inhibitory of mesendoderm induction. Thus, our results indicate that Nodal regulated dusp4 plays a repressive role in mesendoderm induction. PMID:23017456

  8. Microfluidic-based patterning of embryonic stem cells for in vitro development studies.

    PubMed

    Suri, Shalu; Singh, Ankur; Nguyen, Anh H; Bratt-Leal, Andres M; McDevitt, Todd C; Lu, Hang

    2013-12-01

    In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments.

  9. Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development

    SciTech Connect

    Nishikawa, Masaki; Yanagawa, Naomi; Kojima, Nobuhiko; Yuri, Shunsuke; Hauser, Peter V.; Jo, Oak D.; Yanagawa, Norimoto

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer We induced renal lineages from mESCs by following the in vivo developmental cues. Black-Right-Pointing-Pointer We induced nephrogenic intermediate mesoderm by stepwise addition of factors. Black-Right-Pointing-Pointer We induced two types of renal progenitor cells by reciprocal conditioned media. Black-Right-Pointing-Pointer We propose the potential role of CD24 for the enrichment of renal lineage cells. -- Abstract: The in vitro derivation of renal lineage progenitor cells is essential for renal cell therapy and regeneration. Despite extensive studies in the past, a protocol for renal lineage induction from embryonic stem cells remains unestablished. In this study, we aimed to induce renal lineages from mouse embryonic stem cells (mESC) by following in vivo developmental stages, i.e., the induction of mesoderm (Stage I), intermediate mesoderm (Stage II) and renal lineages (Stage III). For stage I induction, in accordance with known signaling pathways involved in mesoderm development in vivo, i.e., Nodal, bone morphogenic proteins (BMPs) and Wnt, we found that the sequential addition of three factors, i.e., Activin-A (A), a surrogate for Nodal signaling, during days 0-2, A plus BMP-4 (4) during days 2-4, and A4 plus lithium (L), a surrogate for Wnt signaling, during days 4-6, was most effective to induce the mesodermal marker, Brachyury. For stage II induction, the addition of retinoic acid (R) in the continuous presence of A4L during days 6-8 was most effective to induce nephrogenic intermediate mesodermal markers, such as Pax2 and Lim1. Under this condition, more than 30% of cells were stained positive for Pax2, and there was a concomitant decrease in the expression of non-mesodermal markers. For stage III induction, in resemblance to the reciprocal induction between ureteric bud (UB) and metanephric mesenchyme (MM) during kidney development, we found that the exposure to conditioned media derived from UB and MM cells was

  10. Nodal Quasiparticle in Pseudogapped Colossal Magnetoresistive Manganites

    SciTech Connect

    Mannella, N.

    2010-06-02

    A characteristic feature of the copper oxide high-temperature superconductors is the dichotomy between the electronic excitations along the nodal (diagonal) and antinodal (parallel to the Cu-O bonds) directions in momentum space, generally assumed to be linked to the d-wave symmetry of the superconducting state. Angle-resolved photoemission measurements in the superconducting state have revealed a quasiparticle spectrum with a d-wave gap structure that exhibits a maximum along the antinodal direction and vanishes along the nodal direction. Subsequent measurements have shown that, at low doping levels, this gap structure persists even in the high-temperature metallic state, although the nodal points of the superconducting state spread out in finite Fermi arcs. This is the so-called pseudogap phase, and it has been assumed that it is closely linked to the superconducting state, either by assigning it to fluctuating superconductivity or by invoking orders which are natural competitors of d-wave superconductors. Here we report experimental evidence that a very similar pseudogap state with a nodal-antinodal dichotomous character exists in a system that is markedly different from a superconductor: the ferromagnetic metallic groundstate of the colossal magnetoresistive bilayer manganite La{sub 1.2}Sr{sub 1.8}Mn{sub 2}O{sub 7}. Our findings therefore cast doubt on the assumption that the pseudogap state in the copper oxides and the nodal-antinodal dichotomy are hallmarks of the superconductivity state.

  11. Nanog-like Regulates Endoderm Formation through the Mxtx2-Nodal Pathway

    PubMed Central

    Xu, Cong; Fan, Zi Peng; Müller, Patrick; Fogley, Rachel; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Xiong, Fengzhu; Torregroza, Ingrid; Evans, Todd; Megason, Sean G.; Daley, George Q.; Schier, Alexander F.; Young, Richard A.; Zon, Leonard I.

    2012-01-01

    SUMMARY In mammalian embryonic stem cells, the acquisition of pluripotency is dependent upon Nanog, but the in vivo analysis of Nanog has been hampered by its requirement for early mouse development. In an effort to examine the role of Nanog in vivo, we identified a zebrafish Nanog ortholog, and found that its knockdown impaired endoderm formation. Genome-wide transcription analysis revealed that nanog-like morphants fail to develop the extra-embryonic yolk syncytial layer (YSL), which produces Nodal required for endoderm induction. We examined the genes that were regulated by Nanog-like, and identified the homeobox gene mxtx2, which is both necessary and sufficient for YSL induction. Chromatin immunoprecipitation assays and genetic studies indicated that Nanog-like directly activates mxtx2, which in turn specifies the YSL lineage by directly activating YSL genes. Our study identifies a Nanog-like-Mxtx2-Nodal pathway and establishes a role for Nanog-like in regulating the formation of the extra-embryonic tissue required for endoderm induction. PMID:22421047

  12. Nodal domains in open microwave systems.

    PubMed

    Kuhl, U; Höhmann, R; Stöckmann, H-J; Gnutzmann, S

    2007-03-01

    Nodal domains are studied both for real psiR and imaginary part psiI of the wave functions of an open microwave cavity and found to show the same behavior as wave functions in closed billiards. In addition we investigate the variation of the number of nodal domains and the signed area correlation by changing the global phase phig according to psiR+ipsiI=eiphig(psiR'+ipsiI'). This variation can be qualitatively, and the correlation quantitatively explained in terms of the phase rigidity characterizing the openness of the billiard.

  13. Nodal domains in open microwave systems

    NASA Astrophysics Data System (ADS)

    Kuhl, U.; Höhmann, R.; Stöckmann, H.-J.; Gnutzmann, S.

    2007-03-01

    Nodal domains are studied both for real ψR and imaginary part ψI of the wave functions of an open microwave cavity and found to show the same behavior as wave functions in closed billiards. In addition we investigate the variation of the number of nodal domains and the signed area correlation by changing the global phase φg according to ψR+iψI=eiφg(ψR'+iψI') . This variation can be qualitatively, and the correlation quantitatively explained in terms of the phase rigidity characterizing the openness of the billiard.

  14. Nodal quasiparticle in pseudogapped colossal magnetoresistive manganites

    NASA Astrophysics Data System (ADS)

    Mannella, N.; Yang, W. L.; Zhou, X. J.; Tanaka, K.; Zheng, H.; Mitchell, J. F.; Zaanen, J.; Devereaux, T. P.; Nagaosa, N.; Hussain, Z.; Shen, Z. X.

    2006-03-01

    In this talk, the result of a recent angle-resolved photoemission spectroscopy (ARPES) investigation which allowed elucidating the controversial nature of the ferromagnetic metallic groundstate in the prototypical colossal magnetoresistive manganite bilayer compound La1.2Sr1.8Mn2O7 will be discussed [1]. The distribution of spectral weight in momentum space exhibits a nodal--antinodal dichotomous character. Quasiparticle excitations have been detected for the first time along the nodal direction (i.e. diagonal), and they are found to determine the metallic transport properties of this compound. The weight of the quasiparticle peak diminishes rapidly while crossing over to the antinodal (i.e. parallel to the Mn--O bonds) parallel sections of the Fermi surface, with the spectra strongly resembling those found in heavily underdoped cuprates high temperature superconductors (HTSC) such as Ca2-xNaxCuO2Cl2 [2]. This dichotomy between the electronic excitations along the nodal and antinodal directions in momentum space was so far considered a characteristic unique feature of the copper oxide HTSC. These findings therefore cast doubt on the assumption that the pseudogap state in the cuprate HTSC and the nodal-antinodal dichotomy are hallmarks of the superconductivity state. [1] N. Mannella et al., Nature 438, 474 (2005) [2] K. M Shen et al., Science 307, 901 (2005).

  15. Nodal quasiparticle in pseudogapped colossal magnetoresistivemanganites

    SciTech Connect

    Mannella, Norman; Yang, Wanli L.; Zhou, Xing Jiang; Zheng, Hong; Mitchell, John F.; Zaanen, Jan; Devereaux, Thomas P.; Nagaosa, Naoto; Hussain, Zahid; Shen, Zhi-Xun

    2008-01-17

    A characteristic feature of the copper oxidehigh-temperaturesuperconductors is the dichotomy between the electronicexcitations along the nodal (diagonal) and antinodal (parallel to the CuO bonds) directions in momentum space, generally assumed to be linked tothe 'd-wave' symmetry of the superconducting state. Angle-resolvedphotoemission measurements in the superconducting state have revealed aquasiparticle spectrum with a d-wave gap structure that exhibits amaximum along the antinodal direction and vanishes along the nodaldirection1. Subsequent measurements have shown that, at low dopinglevels, this gap structure persists even in the high-temperature metallicstate, although the nodal points of the superconducting state spread outin finite 'Fermi arcs'2. This is the so-called pseudogap phase, and ithas been assumed that it is closely linked to the superconducting state,either by assigning it to fluctuating superconductivity3 or by invokingorders which are natural competitors of d-wave superconductors4, 5. Herewe report experimental evidence that a very similar pseudogap state witha nodal-antinodal dichotomous character exists in a system that ismarkedly different from a superconductor: the ferromagnetic metallicgroundstate of the colossal magnetoresistive bilayer manganiteLa1.2Sr1.8Mn2O7. Our findings therefore cast doubt on the assumption thatthe pseudogap state in the copper oxides and the nodal-antinodaldichotomy are hallmarks of the superconductivity state.

  16. A System of Repressor Gradients Spatially Organizes the Boundaries of “Morphogen-dependent” Target Genes

    PubMed Central

    Chen, Hongtao; Xu, Zhe; Mei, Constance; Yu, Danyang; Small, Stephen

    2012-01-01

    Summary The homeodomain (HD) protein Bicoid (Bcd) is thought to function as a gradient morphogen that positions boundaries of target genes via threshold-dependent activation mechanisms. Here we analyze 66 Bcd-dependent regulatory elements, and show that their boundaries are positioned primarily by repressive gradients that antagonize Bcd-mediated activation. A major repressor is the pair-rule protein Runt, which is expressed in an opposing gradient, and is necessary and sufficient for limiting Bcd-dependent activation. Evidence is presented that Runt functions with the maternal repressor Capicua and the gap protein Kruppel as the principal components of a repression system that correctly orders boundaries throughout the anterior half of the embryo. These results put conceptual limits on the Bcd morphogen hypothesis, and demonstrate how the Bcd gradient functions within the gene network that patterns the embryo. PMID:22541432

  17. Intrinsic Noise Profoundly Alters the Dynamics and Steady State of Morphogen-Controlled Bistable Genetic Switches

    PubMed Central

    Page, Karen M.

    2016-01-01

    During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules—morphogens—guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms. Here, we explore the dynamics of the toggle switch and use exact numerical simulations of the kinetic reactions, the corresponding Chemical Langevin Equation, and Minimum Action Path theory to establish a framework for studying the effect of gene expression noise on patterning time and boundary position. This provides insight into the time scale, gene expression trajectories and directionality of stochastic switching events between cell states. Taking gene expression noise into account predicts that the final boundary position of a morphogen-induced toggle switch, although robust to changes in the details of the noise, is distinct from that of the deterministic system. Moreover, the dramatic increase in patterning time close to the boundary predicted from the deterministic case is substantially reduced. The resulting stochastic switching introduces differences in patterning time along the morphogen gradient that result in a patterning wave propagating away from the morphogen source with a velocity determined by the intrinsic noise. The wave sharpens and slows as it advances and may never reach steady state in a biologically relevant time. This could explain experimentally observed dynamics of pattern formation. Together the analysis reveals the importance of dynamical transients for understanding morphogen-driven transcriptional networks and indicates that gene expression noise can qualitatively

  18. Color-pattern analysis of eyespots in butterfly wings: a critical examination of morphogen gradient models.

    PubMed

    Otaki, Joji M

    2011-06-01

    Butterfly wing color patterns consist of many color-pattern elements such as eyespots. It is believed that eyespot patterns are determined by a concentration gradient of a single morphogen species released by diffusion from the prospective eyespot focus in conjunction with multiple thresholds in signal-receiving cells. As alternatives to this single-morphogen model, more flexible multiple-morphogen model and induction model can be proposed. However, the relevance of these conceptual models to actual eyespots has not been examined systematically. Here, representative eyespots from nymphalid butterflies were analyzed morphologically to determine if they are consistent with these models. Measurement of ring widths of serial eyespots from a single wing surface showed that the proportion of each ring in an eyespot is quite different among homologous rings of serial eyespots of different sizes. In asymmetric eyespots, each ring is distorted to varying degrees. In extreme cases, only a portion of rings is expressed remotely from the focus. Similarly, there are many eyespots where only certain rings are deleted, added, or expanded. In an unusual case, the central area of an eyespot is composed of multiple "miniature eyespots," but the overall macroscopic eyespot structure is maintained. These results indicate that each eyespot ring has independence and flexibility to a certain degree, which is less consistent with the single-morphogen model. Considering a "periodic eyespot", which has repeats of a set of rings, damage-induced eyespots in mutants, and a scale-size distribution pattern in an eyespot, the induction model is the least incompatible with the actual eyespot diversity. PMID:21627450

  19. Color-pattern analysis of eyespots in butterfly wings: a critical examination of morphogen gradient models.

    PubMed

    Otaki, Joji M

    2011-06-01

    Butterfly wing color patterns consist of many color-pattern elements such as eyespots. It is believed that eyespot patterns are determined by a concentration gradient of a single morphogen species released by diffusion from the prospective eyespot focus in conjunction with multiple thresholds in signal-receiving cells. As alternatives to this single-morphogen model, more flexible multiple-morphogen model and induction model can be proposed. However, the relevance of these conceptual models to actual eyespots has not been examined systematically. Here, representative eyespots from nymphalid butterflies were analyzed morphologically to determine if they are consistent with these models. Measurement of ring widths of serial eyespots from a single wing surface showed that the proportion of each ring in an eyespot is quite different among homologous rings of serial eyespots of different sizes. In asymmetric eyespots, each ring is distorted to varying degrees. In extreme cases, only a portion of rings is expressed remotely from the focus. Similarly, there are many eyespots where only certain rings are deleted, added, or expanded. In an unusual case, the central area of an eyespot is composed of multiple "miniature eyespots," but the overall macroscopic eyespot structure is maintained. These results indicate that each eyespot ring has independence and flexibility to a certain degree, which is less consistent with the single-morphogen model. Considering a "periodic eyespot", which has repeats of a set of rings, damage-induced eyespots in mutants, and a scale-size distribution pattern in an eyespot, the induction model is the least incompatible with the actual eyespot diversity.

  20. Organoids and the genetically encoded self-assembly of embryonic stem cells.

    PubMed

    Turner, David A; Baillie-Johnson, Peter; Martinez Arias, Alfonso

    2016-02-01

    Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to self-organization, as often suggested, but rather to a process of genetically encoded self-assembly where genetic programs encode and control the emergence of biological structures.

  1. Novel Metrics to Characterize Embryonic Elongation of the Nematode Caenorhabditis elegans.

    PubMed

    Martin, Emmanuel; Rocheleau-Leclair, Olivier; Jenna, Sarah

    2016-03-28

    Dissecting the signaling pathways that control the alteration of morphogenic processes during embryonic development requires robust and sensitive metrics. Embryonic elongation of the nematode Caenorhabditis elegans is a late developmental stage consisting of the elongation of the embryo along its longitudinal axis. This developmental stage is controlled by intercellular communication between hypodermal cells and underlying body-wall muscles. These signaling mechanisms control the morphology of hypodermal cells by remodeling the cytoskeleton and the cell-cell junctions. Measurement of embryonic lethality and developmental arrest at larval stages as well as alteration of cytoskeleton and cell-cell adhesion structures in hypodermal and muscle cells are classical phenotypes that have been used for more than 25 years to dissect these signaling pathways. Recent studies required the development of novel metrics specifically targeting either early or late elongation and characterizing morphogenic defects along the antero-posterior axis of the embryo. Here, we provide detailed protocols enabling the accurate measurement of the length and the width of the elongating embryos as well as the length of synchronized larvae. These methods constitute useful tools to identify genes controlling elongation, to assess whether these genes control both early and late phases of this stage and are required evenly along the antero-posterior axis of the embryo.

  2. Transcriptomic analysis of Nodal- and BMP-associated genes during juvenile development of the sea urchin Heliocidaris erythrogramma.

    PubMed

    Byrne, Maria; Koop, Demian; Cisternas, Paula; Strbenac, Dario; Yang, Jean Yee Hwa; Wray, Gregory A

    2015-12-01

    Understanding the unusual radial body plan of echinoderms and its relationship to the bilateral plan of other deuterostomes remains a challenge. The molecular processes of embryonic and early larval development in sea urchins are well characterised, but those giving rise to the adult and its radial body remain poorly studied. We used the developmental transcriptome generated for Heliocidaris erythrogramma, a species that forms the juvenile soon after gastrulation, to investigate changes in gene expression underlying radial body development. As coelomogenesis is key to the development of pentamery and juvenile formation on the left side of the larva, we focussed on genes associated with the nodal and BMP2/4 network that pattern this asymmetry. We identified 46 genes associated with this Nodal and BMP2/4 signalling network, and determined their expression profiles from the gastrula, through to rudiment development, metamorphosis and the fully formed juvenile. Genes associated with Nodal signalling shared similar expression profiles, indicating that they may have a regulatory relationship in patterning morphogenesis of the juvenile sea urchin. Similarly, many genes associated with BMP2/4 signalling had similar expression profiles through juvenile development. Further examination of the roles of Nodal- and BMP2/4-associated genes is required to determine function and whether the gene expression profiles seen in H. erythrogramma are due to ongoing activity of gene networks established during early development, or to redeployment of regulatory cassettes to pattern the adult radial body plan.

  3. Combination of Controllably Released Platelet Rich Plasma Alginate Beads and Bone Morphogenic Protein-2 Gene-Modified Mesenchymal Stem Cells for Bone Regeneration

    PubMed Central

    Fernandes, Gabriela; Wang, Changdong; Yuan, Xue; Liu, Zunpeng; Dziak, Rosemary; Yang, Shuying

    2016-01-01

    Background Platelet rich plasma (PRP) consists of platelet derived growth factor (PDGF) and Transforming growth factor-beta (TGF-β) that increase cell proliferation of mesenchymal stem cells (MSCs), whereas, bone morphogenic Protein-2 (BMP2) promotes osteogenic differentiation of MSCs. However, the high degradation rate of fibrin leads to the dissociation of cytokines even before the process of bone regeneration has begun. Hence, for the first time, we studied the combined effect of sustained released PRP from alginate beads on BMP2 modified MSCs osteogenic differentiation in vitro and of sustained PRP alone on a fracture defect model ex vivo as well as its effect on the calvarial suture closure. Methods After optimizing the concentration of alginate for the microspheres, the osteogenic and mineralization effect of PRP and BMP2 in combinations on MSCs was studied. A self-setting alginate hydrogel carrying PRP was tested on a femur defect model ex-vivo. The effect of PRP was studied on the closure of the embryonic (E15) mouse calvaria sutures ex vivo. Results Increase of PRP concentration promoted cellular proliferation of MSCs. 2.5%–10% of PRP displayed gradually increased ALP activity on the cells in a dose dependent manner. Sustained release PRP and BMP2 demonstrated a significantly higher ALP and mineralization activity (p<0.05). The radiographs of alginate hydrogel with PRP treated bone demonstrated a nearly complete healing of the fracture and the histological sections of the embryonic calvaria revealed that PRP leads to suture fusion. Conclusions Sustained release of PRP along with BMP2 gene modified MSCs can significantly promote bone regeneration. PMID:26745613

  4. Small renal tumor with lymph nodal enlargement: A histopathological surprise

    PubMed Central

    Thottathil, Mujeeburahiman; Verma, Ashish; D’souza, Nischith; Khan, Altaf

    2016-01-01

    Renal cancer with lymph nodal mass on the investigation is clinically suggestive of an advanced tumor. Small renal cancers are not commonly associated with lymph nodal metastasis. Association of renal cell carcinoma with renal tuberculosis (TB) in the same kidney is also rare. We report here a case of small renal cancer with multiple hilar and paraaortic lymph nodes who underwent radical nephrectomy, and histopathology report showed renal and lymph nodal TB too. PMID:27453671

  5. Nodal integral method for transient heat conduction in a cylinder

    SciTech Connect

    Esser, P.D. )

    1993-01-01

    The accuracy and efficiency of nodal solution methods are well established for neutron diffusion in a variety of geometries, as well as for heat transfer and fluid flow in rectangular coordinates. This paper describes the development of a nodal integral method to solve the transient heat conduction equation in cylindrical geometry. Results for a test problem with an analytical solution indicate that the nodal solution provides higher accuracy than a conventional implicit finite difference scheme, while maintaining similar stability characteristics.

  6. Topological surface states in nodal superconductors.

    PubMed

    Schnyder, Andreas P; Brydon, Philip M R

    2015-06-24

    Topological superconductors have become a subject of intense research due to their potential use for technical applications in device fabrication and quantum information. Besides fully gapped superconductors, unconventional superconductors with point or line nodes in their order parameter can also exhibit nontrivial topological characteristics. This article reviews recent progress in the theoretical understanding of nodal topological superconductors, with a focus on Weyl and noncentrosymmetric superconductors and their protected surface states. Using selected examples, we review the bulk topological properties of these systems, study different types of topological surface states, and examine their unusual properties. Furthermore, we survey some candidate materials for topological superconductivity and discuss different experimental signatures of topological surface states.

  7. The AN neutron transport by nodal diffusion

    SciTech Connect

    Barbarino, A.; Tomatis, D.

    2013-07-01

    The two group diffusion model combined to a nodal approach in space is the preferred scheme for the industrial simulation of nuclear water reactors. The main selling point is the speed of computation, allowing a large number of parametric studies. Anyway, the drawbacks of the underlying diffusion equation may arise with highly heterogeneous interfaces, often encountered in modern UO{sub 2} and MO{sub x} fuel loading patterns, and boron less controlled systems. This paper aims at showing how the simplified AN transport model, equivalent to the well known SPN, can be implemented in standard diffusion codes with minor modifications. Some numerical results are illustrated. (authors)

  8. Compactin enhances osteogenesis in murine embryonic stem cells.

    PubMed

    Phillips, B W; Belmonte, N; Vernochet, C; Ailhaud, G; Dani, C

    2001-06-01

    Embryonic stem (ES) cells have the capacity to differentiate into various cell types in vitro. In this study, we show that retinoic acid is important for the commitment of ES cells into osteoblasts. Culturing retinoic acid treated ES cells in the presence of the osteogenic supplements ascorbic acid and beta-glycerophosphate resulted in the expression of several osteoblast marker genes, osteocalcin, alkaline phosphatase, and osteopontin. However, there was only a slight amount of mineralized matrix secretion. Addition of bone morphogenic protein-2 or compactin, a drug of the statin family of HMG-CoA reductase inhibitors, resulted in a greatly enhanced formation of bone nodules. Compactin did not modify the expression of osteogenic markers, but at the late stage of differentiation promoted an increase in BMP-2 expression. These results establish ES-cell derived osteogenesis as an effective model system to study the molecular mechanisms by which the statin compactin promotes osteoblastic differentiation and bone nodule formation. PMID:11394905

  9. Fucoidan Promotes Early Step of Cardiac Differentiation from Human Embryonic Stem Cells and Long-Term Maintenance of Beating Areas

    PubMed Central

    Hamidi, Sofiane; Letourneur, Didier; Aid-Launais, Rachida; Di Stefano, Antonio; Vainchenker, William; Norol, Françoise

    2014-01-01

    Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human embryonic stem cells (hESCs) differentiation toward the cardiac lineage. A macroporous (pore 200 μm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and transforming growth factor (TGFβ) followed by tumor necrosis factor (TNFα), an effector of cardiopoietic priming, we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of the 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (p<0.05), MEF2C (p<0.01), and GATA4 (p<0.01), confirmed by flow cytometry analysis for MEF2C and NKX2.5. The ability of Fucoidan scaffolds to locally concentrate and slowly release TGFβ and TNFα was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher atrial natriuretic factor (ANF) expression (p<0.001), although only rare beating areas were observed. We postulated that absence of mechanical stress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric α-actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that

  10. Anomalous thermodynamic power laws in nodal superconductors

    NASA Astrophysics Data System (ADS)

    Quintanilla, Jorge; Mazidian, Bayan; Annett, James F.; Hillier, Adrian D.

    2013-03-01

    Unconventional superconductors are frequently identified by the observation of power law behaviour on low temperature thermodynamic properties such as specific heat. These power laws generally derive from the linear spectrum near points or lines of zeros, or nodes, in the superconducting energy gap on the Fermi surface. Here we show that, in addition to the usual point and line nodes, a much wider class of different nodal types can occur. Some of these new types of nodes typically occur when there are transitions between different types of gap node topology, for example when point or line nodes first appear as a function of some physical parameter. We derive anomalous, non-integer thermodynamic power laws associated with these new nodal types and predict their occurrence in iron pnictide superconductors and in the noncentrosymmetric system Li2Pd3-xPtxB. This works was supported by EPSRC and STFC (U.K.) J.Q. gratefully acknowledges funding from HEFCE and STFC through the South-East Physics network (SEPnet).

  11. Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia

    PubMed Central

    Seijo, Irene; Andrés, Germán; Rodríguez-Navas, Carmen; González-Méndez, Laura; Guerrero, Isabel

    2013-01-01

    Summary Hedgehog (Hh) signalling is important in development, stem cell biology and disease. In a variety of tissues, Hh acts as a morphogen to regulate growth and cell fate specification. Several hypotheses have been proposed to explain morphogen movement, one of which is transport via filopodia-like protrusions called cytonemes. Here, we analyse the mechanism underlying Hh movement in the wing disc and the abdominal epidermis of Drosophila. We show that, in both epithelia, cells generate cytonemes in regions of Hh signalling. These protrusions are actin-based and span several cell diameters. Various Hh signalling components localise to cytonemes, as well as to punctate structures that move along cytonemes and are probably exovesicles. Using in vivo imaging, we show that cytonemes are dynamic structures and that Hh gradient establishment correlates with cytoneme formation in space and time. Indeed, mutant conditions that affect cytoneme formation reduce both cytoneme length and Hh gradient length. Our results suggest that cytoneme-mediated Hh transport is the mechanistic basis for Hh gradient formation. PMID:24121526

  12. Butterfly eyespot patterns: evidence for specification by a morphogen diffusion gradient.

    PubMed

    Monteiro, A; French, V; Smit, G; Brakefield, P M; Metz, J A

    2001-01-01

    In this paper we describe a test for Nijhout's (1978, 1980a) hypothesis that the eyespot patterns on butterfly wings are the result of a threshold reaction of the epidermal cells to a concentration gradient of a diffusing degradable morphogen produced by focal cells at the centre of the future eyespot. The wings of the nymphalid butterfly, Bicyclus anynana, have a series of eyespots. each composed of a white pupil, a black disc and a gold outer ring. In earlier extirpation and transplantation experiments (Nijhout 1980a; French and Brakefield, 1995) it has been established that these eyespots are indeed organised around groups of signalling cells active during the first hours of pupal development. If these cells were to supply the positional information for eyespot formation in accordance with Nijhout's diffusion-degradation gradient model, then, when two foci are close together. the signals should sum, and this effect should be apparent in the detailed shape of the resulting pigment pattern. We give an equation for the form of the contours that would be obtained in this manner. We use this to test the morphogen gradient hypothesis on measurements of the outlines of fused eyespots obtained either by grafting focal cells close together, or by using a mutation (Spotty) that produces adjacent fused eyespots. The contours of the fused patterns were found to satisfy our equation, thus corroborating Nijhout's hypothesis to the extent possible with this particular type of experiment. PMID:11450809

  13. The structure and morphogenic changes of antennae of Matsucoccus matsumurae (Hemiptera: Coccoidea: Matsucoccidae) in different instars.

    PubMed

    Wang, Xu; Xie, Yingping; Zhang, Yanfeng; Liu, Weimin; Wu, Jun

    2016-05-01

    To better understand the functioning and morphogenic changes of the antennae of Matsucoccus matsumurae (Kuwana) in different instars, the antennae are examined using light microscopy, scanning and transmission electron microscopy. The results show that the antennae of M. matsumurae display three different styles in morphology and sensillar distribution in different instars. The antennae of first instar nymphs are relatively simple, including one campaniform sensillum (Ca), four smooth aporous trichoid sensilla (SAt), two intersegmental sensilla (Ins), two coeloconic sensilla (Co), three multiporous pegs (Mp) and four uniporous pegs (Up). The antennae of adult females and third instar male nymphs both possess similar antennae, and exhibit seven types of sensilla. Adult female antennae have in total 82-108 sensilla, including 9-16 Böhm's bristle (Bb), 3-7 Ca, 50-75 SAt, 0-3 Ins, 3-10 Co, 8 Mp and 5 Up, whereas third instar male nymph antennae possess approximately 62-79 sensilla. Adult male antennae are the most developed, possessing 259-312 sensilla, including 7-15 Bb, 2-5 Ca, 7-11 grooved aporous trichoid sensilla, 4-9 SAt, 0-3 Ins, 2-7 Co, 23-29 knobbed seta sensilla, 179-230 multiporous trichoid sensilla and 8 Mp. Based on these results, the main functions and morphogenic changes of antennae M. matsumurae in different instars are discussed.

  14. Butterfly eyespot patterns: evidence for specification by a morphogen diffusion gradient.

    PubMed

    Monteiro, A; French, V; Smit, G; Brakefield, P M; Metz, J A

    2001-01-01

    In this paper we describe a test for Nijhout's (1978, 1980a) hypothesis that the eyespot patterns on butterfly wings are the result of a threshold reaction of the epidermal cells to a concentration gradient of a diffusing degradable morphogen produced by focal cells at the centre of the future eyespot. The wings of the nymphalid butterfly, Bicyclus anynana, have a series of eyespots. each composed of a white pupil, a black disc and a gold outer ring. In earlier extirpation and transplantation experiments (Nijhout 1980a; French and Brakefield, 1995) it has been established that these eyespots are indeed organised around groups of signalling cells active during the first hours of pupal development. If these cells were to supply the positional information for eyespot formation in accordance with Nijhout's diffusion-degradation gradient model, then, when two foci are close together. the signals should sum, and this effect should be apparent in the detailed shape of the resulting pigment pattern. We give an equation for the form of the contours that would be obtained in this manner. We use this to test the morphogen gradient hypothesis on measurements of the outlines of fused eyespots obtained either by grafting focal cells close together, or by using a mutation (Spotty) that produces adjacent fused eyespots. The contours of the fused patterns were found to satisfy our equation, thus corroborating Nijhout's hypothesis to the extent possible with this particular type of experiment.

  15. Topological surface states in nodal superconductors.

    PubMed

    Schnyder, Andreas P; Brydon, Philip M R

    2015-06-24

    Topological superconductors have become a subject of intense research due to their potential use for technical applications in device fabrication and quantum information. Besides fully gapped superconductors, unconventional superconductors with point or line nodes in their order parameter can also exhibit nontrivial topological characteristics. This article reviews recent progress in the theoretical understanding of nodal topological superconductors, with a focus on Weyl and noncentrosymmetric superconductors and their protected surface states. Using selected examples, we review the bulk topological properties of these systems, study different types of topological surface states, and examine their unusual properties. Furthermore, we survey some candidate materials for topological superconductivity and discuss different experimental signatures of topological surface states. PMID:26000466

  16. Experience with advanced nodal codes at YAEC

    SciTech Connect

    Cacciapouti, R.J.

    1990-01-01

    Yankee Atomic Electric Company (YAEC) has been performing reload licensing analysis since 1969. The basic pressurized water reactor (PWR) methodology involves the use of LEOPARD for cross-section generation, PDQ for radial power distributions and integral control rod worth, and SIMULATE for axial power distributions and differential control rod worth. In 1980, YAEC began performing reload licensing analysis for the Vermont Yankee boiling water reactor (BWR). The basic BWR methodology involves the use of CASMO for cross-section generation and SIMULATE for three-dimensional power distributions. In 1986, YAEC began investigating the use of CASMO-3 for cross-section generation and the advanced nodal code SIMULATE-3 for power distribution analysis. Based on the evaluation, the CASMO-3/SIMULATE-3 methodology satisfied all requirements. After careful consideration, the cost of implementing the new methodology is expected to be offset by reduced computing costs, improved engineering productivity, and fuel-cycle performance gains.

  17. Radar response from vegetation with nodal structure

    NASA Technical Reports Server (NTRS)

    Blanchard, B. J.; Oneill, P. E.

    1984-01-01

    Radar images from the SEASAT synthetic aperture radar (SAR) produced unusually high returns from corn and sorghum fields, which seem to indicate a correlation between nodal separation in the stalk and the wavelength of the radar. These images also show no difference in return from standing or harvested corn. Further investigation using images from the Shuttle Imaging Radar (SIR-A) substantiated these observations and showed a degradation of the high return with time after harvest. From portions of corn and sweet sorghum stalks that were sampled to measure stalk water content, it was determined that near and after maturity the water becomes more concentrated in the stalk nodes. The stalk then becomes a linear sequence of alternating dielectrics as opposed to a long slender cylinder with uniform dielectric properties.

  18. [A Complex Morpho-Histological Approach to the In Vitro Study of Morphogenic Structures in a Wheat Anther Culture].

    PubMed

    Seldimirova, O A; Titova, G E; Kruglova, N N

    2016-01-01

    The external morphological and internal histological features of morphogenic structures (embryoids, calli with embryoids, and calli with buds and roots) have been studied in vitro in a wheat anther culture by light microscopy. The results of this study have been compared with data obtained earlier by scanning electron microscopy.

  19. Controlled delivery of sonic hedgehog morphogen and its potential for cardiac repair.

    PubMed

    Johnson, Noah Ray; Wang, Yadong

    2013-01-01

    The morphogen Sonic hedgehog (Shh) holds great promise for repair or regeneration of tissues suffering ischemic injury, however clinical translation is limited by its short half-life in the body. Here, we describe a coacervate delivery system which incorporates Shh, protects it from degradation, and sustains its release for at least 3 weeks. Shh released from the coacervate stimulates cardiac fibroblasts to upregulate the expression of multiple trophic factors including VEGF, SDF-1α, IGF-1, and Shh itself, for at least 48 hours. Shh coacervate also demonstrates cytoprotective effects for cardiomyocytes in a hydrogen peroxide-induced oxidative stress environment. In each of these studies the bioactivity of the Shh coacervate is enhanced compared to free Shh. These results warrant further investigation of the in vivo efficacy of Shh coacervate for cardiac repair.

  20. A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

    PubMed

    Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

    2012-02-23

    The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development.

  1. Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

    PubMed Central

    Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

    2012-01-01

    Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

  2. Isolation of bovine corneal keratan sulfate and its growth factor and morphogen binding.

    PubMed

    Weyers, Amanda; Yang, Bo; Solakyildirim, Kemal; Yee, Vienna; Li, Lingyun; Zhang, Fuming; Linhardt, Robert J

    2013-05-01

    Keratan sulfate (KS) is an important glycosaminoglycan that is found in cartilage, reproductive tissues, and neural tissues. Corneal KS glycosaminoglycan is found N-linked to lumican, keratocan and mimecan proteoglycans, and has been widely studied by investigators interested in corneal development and diseases. Recently, the availability of corneal KS has become severely limited, owing to restrictions on the shipment of bovine central nervous system byproducts across international borders in an effort to prevent additional cases of mad cow disease. We report a simple method for the purification of multi-milligram quantities of bovine corneal KS, and characterize its structural properties. We also examined its protein-binding properties, and discovered that corneal KS bound with high affinity to fibroblast growth factor-2 and sonic hedgehog, a growth factor and a morphogen involved in corneal development and healing. PMID:23402351

  3. Self-construction of supramolecular polyrotaxane films by an electrotriggered morphogen-driven process.

    PubMed

    Rydzek, Gaulthier; Garnier, Tony; Schaaf, Pierre; Voegel, Jean-Claude; Senger, Bernard; Frisch, Benoît; Haikel, Youssef; Petit, Corinne; Schlatter, Guy; Jierry, Loïc; Boulmedais, Fouzia

    2013-08-27

    The design of films using a one-pot process has recently attracted increasing interest in the field of polymer thin film formation. Herein we describe the preparation of one-pot supramolecular polyrotaxane (PRX) films using the morphogen-driven self-construction process. This one-pot buildup strategy where the film growth is triggered by the electrochemical formation and diffusion of a catalyst in close vicinity of the substrate has recently been introduced by our group. A one-pot mixture was used that contained (i) poly(acrylic acid) (PAA) functionalized by azide groups grafted on the polymer chain through oligo(ethylene glycol) (EG) arms, leading to PAA-EG13-N3, (ii) cyclodextrins (α and β CD), as macrocycles that can be threaded along EG arms, (iii) alkyne-functionalized stoppers (ferrocene or adamantane), to cap the PRX assembly by click chemistry, and (iv) copper sulfate. The one-pot mixture solution was brought into contact with a gold electrode. Cu(I), the morphogen, was generated electrochemically from Cu(II) at the electrode/one-pot solution interface. This electrotriggered click reaction leads to the capping of polypseudorotaxane yielding to PRXs. The PRXs can self-assemble through lateral supramolecular interactions to form aggregates and ensure the cohesion of the film. The film buildup was investigated using different types of CD and alkyne functionalized stoppers. Supramolecular PRX aggregates were characterized by X-ray diffraction measurements. The film topographies were imaged by atomic force microscopy. The influence of the concentration in CD and the presence of a competitor were studied as well. The stability of the resulting film was tested in contact with 8 M urea and during the electrochemical oxidation of ferrocene. PMID:23895332

  4. Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung

    PubMed Central

    Bokka, Kishore K.; Jesudason, Edwin C.; Lozoya, Oswaldo A.; Guilak, Farshid; Warburton, David; Lubkin, Sharon R.

    2015-01-01

    Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 ± 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs. PMID:26147967

  5. Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung.

    PubMed

    Bokka, Kishore K; Jesudason, Edwin C; Lozoya, Oswaldo A; Guilak, Farshid; Warburton, David; Lubkin, Sharon R

    2015-01-01

    Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 ± 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs. PMID:26147967

  6. Tunable Weyl Points in Periodically Driven Nodal Line Semimetals.

    PubMed

    Yan, Zhongbo; Wang, Zhong

    2016-08-19

    Weyl semimetals and nodal line semimetals are characterized by linear band touching at zero-dimensional points and one-dimensional lines, respectively. We predict that a circularly polarized light drives nodal line semimetals into Weyl semimetals. The Floquet Weyl points thus obtained are tunable by the incident light, which enables investigations of them in a highly controllable manner. The transition from nodal line semimetals to Weyl semimetals is accompanied by the emergence of a large and tunable anomalous Hall conductivity. Our predictions are experimentally testable by transport measurement in film samples or by pump-probe angle-resolved photoemission spectroscopy. PMID:27588882

  7. NODAL — The second life of the accelerator control language

    NASA Astrophysics Data System (ADS)

    Cuisinier, G.; Perriollat, F.; Ribeiro, P.; Kagarmanov, A.; Kovaltsov, V.

    1994-12-01

    NODAL has been a popular interpreter language for accelerator controls since the beginning of the 1970s. NODAL has been rewritten in the C language to be easily portable to the different computer platforms which are in use in accelerator controls. The paper describes the major features of this new version of NODAL, the major software packages which are available through this implementation, the platforms on which it is currently running, and some relevant performances. The experience gained during the rejuvenation project of the CERN accelerator control systems is presented. The benefit of this is discussed, in particular in a view of the prevailing strong constraints in personnel and money resources.

  8. Tunable Weyl Points in Periodically Driven Nodal Line Semimetals

    NASA Astrophysics Data System (ADS)

    Yan, Zhongbo; Wang, Zhong

    2016-08-01

    Weyl semimetals and nodal line semimetals are characterized by linear band touching at zero-dimensional points and one-dimensional lines, respectively. We predict that a circularly polarized light drives nodal line semimetals into Weyl semimetals. The Floquet Weyl points thus obtained are tunable by the incident light, which enables investigations of them in a highly controllable manner. The transition from nodal line semimetals to Weyl semimetals is accompanied by the emergence of a large and tunable anomalous Hall conductivity. Our predictions are experimentally testable by transport measurement in film samples or by pump-probe angle-resolved photoemission spectroscopy.

  9. A semianalytic two-group nodal model for SIMULATE-3

    SciTech Connect

    Esser, P.D.; Smith, K.S. )

    1993-01-01

    Light water reactor (LWR) cores containing highly enriched ([ge] 10% Pu) mixed-oxide (MOX) fuel exhibit steep thermal flux gradients near MOX-UO[sub 2] assembly interfaces. The fourth-order polynomial representation of the internodal flux used in many polynomial nodal methods (including the QPANDA nodal model in the SIMULATE-3 core analysis code) has already been verified against low-enriched MOX fuel but cannot accurately portray the severe flux variations near highly enriched MOX interfaces. This paper describes the development of an enhanced nodal model that includes transcendental components in the thermal flux profile.

  10. The genetics of nodal marginal zone lymphoma.

    PubMed

    Spina, Valeria; Khiabanian, Hossein; Messina, Monica; Monti, Sara; Cascione, Luciano; Bruscaggin, Alessio; Spaccarotella, Elisa; Holmes, Antony B; Arcaini, Luca; Lucioni, Marco; Tabbò, Fabrizio; Zairis, Sakellarios; Diop, Fary; Cerri, Michaela; Chiaretti, Sabina; Marasca, Roberto; Ponzoni, Maurilio; Deaglio, Silvia; Ramponi, Antonio; Tiacci, Enrico; Pasqualucci, Laura; Paulli, Marco; Falini, Brunangelo; Inghirami, Giorgio; Bertoni, Francesco; Foà, Robin; Rabadan, Raul; Gaidano, Gianluca; Rossi, Davide

    2016-09-01

    Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification.

  11. The genetics of nodal marginal zone lymphoma

    PubMed Central

    Spina, Valeria; Khiabanian, Hossein; Messina, Monica; Monti, Sara; Cascione, Luciano; Bruscaggin, Alessio; Spaccarotella, Elisa; Holmes, Antony B.; Arcaini, Luca; Lucioni, Marco; Tabbò, Fabrizio; Zairis, Sakellarios; Diop, Fary; Cerri, Michaela; Chiaretti, Sabina; Marasca, Roberto; Ponzoni, Maurilio; Deaglio, Silvia; Ramponi, Antonio; Tiacci, Enrico; Pasqualucci, Laura; Paulli, Marco; Falini, Brunangelo; Inghirami, Giorgio; Bertoni, Francesco; Foà, Robin; Rabadan, Raul; Gaidano, Gianluca

    2016-01-01

    Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification. PMID:27335277

  12. The genetics of nodal marginal zone lymphoma.

    PubMed

    Spina, Valeria; Khiabanian, Hossein; Messina, Monica; Monti, Sara; Cascione, Luciano; Bruscaggin, Alessio; Spaccarotella, Elisa; Holmes, Antony B; Arcaini, Luca; Lucioni, Marco; Tabbò, Fabrizio; Zairis, Sakellarios; Diop, Fary; Cerri, Michaela; Chiaretti, Sabina; Marasca, Roberto; Ponzoni, Maurilio; Deaglio, Silvia; Ramponi, Antonio; Tiacci, Enrico; Pasqualucci, Laura; Paulli, Marco; Falini, Brunangelo; Inghirami, Giorgio; Bertoni, Francesco; Foà, Robin; Rabadan, Raul; Gaidano, Gianluca; Rossi, Davide

    2016-09-01

    Nodal marginal zone lymphoma (NMZL) is a rare, indolent B-cell tumor that is distinguished from splenic marginal zone lymphoma (SMZL) by the different pattern of dissemination. NMZL still lacks distinct markers and remains orphan of specific cancer gene lesions. By combining whole-exome sequencing, targeted sequencing of tumor-related genes, whole-transcriptome sequencing, and high-resolution single nucleotide polymorphism array analysis, we aimed at disclosing the pathways that are molecularly deregulated in NMZL and we compare the molecular profile of NMZL with that of SMZL. These analyses identified a distinctive pattern of nonsilent somatic lesions in NMZL. In 35 NMZL patients, 41 genes were found recurrently affected in ≥3 (9%) cases, including highly prevalent molecular lesions of MLL2 (also known as KMT2D; 34%), PTPRD (20%), NOTCH2 (20%), and KLF2 (17%). Mutations of PTPRD, a receptor-type protein tyrosine phosphatase regulating cell growth, were enriched in NMZL across mature B-cell tumors, functionally caused the loss of the phosphatase activity of PTPRD, and were associated with cell-cycle transcriptional program deregulation and increased proliferation index in NMZL. Although NMZL shared with SMZL a common mutation profile, NMZL harbored PTPRD lesions that were otherwise absent in SMZL. Collectively, these findings provide new insights into the genetics of NMZL, identify PTPRD lesions as a novel marker for this lymphoma across mature B-cell tumors, and support the distinction of NMZL as an independent clinicopathologic entity within the current lymphoma classification. PMID:27335277

  13. Nodal Solutions for Supercritical Laplace Equations

    NASA Astrophysics Data System (ADS)

    Dalbono, Francesca; Franca, Matteo

    2016-11-01

    In this paper we study radial solutions for the following equation Δ u(x)+f (u(x), |x|) = 0, where {x in {Rn}}, n > 2, f is subcritical for r small and u large and supercritical for r large and u small, with respect to the Sobolev critical exponent {2^{*} = 2n/n-2}. The solutions are classified and characterized by their asymptotic behaviour and nodal properties. In an appropriate super-linear setting, we give an asymptotic condition sufficient to guarantee the existence of at least one ground state with fast decay with exactly j zeroes for any j ≥ 0. Under the same assumptions, we also find uncountably many ground states with slow decay, singular ground states with fast decay and singular ground states with slow decay, all of them with exactly j zeroes. Our approach, based on Fowler transformation and invariant manifold theory, enables us to deal with a wide family of potentials allowing spatial inhomogeneity and a quite general dependence on u. In particular, for the Matukuma-type potential, we show a kind of structural stability.

  14. Classification, Electrophysiological Features and Therapy of Atrioventricular Nodal Reentrant Tachycardia

    PubMed Central

    Josephson, Mark E

    2016-01-01

    Atrioventricular nodal reentrant tachycardia (AVNRT) should be classified as typical or atypical. The term ‘fast-slow AVNRT’ is rather misleading. Retrograde atrial activation during tachycardia should not be relied upon as a diagnostic criterion. Both typical and atypical atrioventricular nodal reentrant tachycardia are compatible with varying retrograde atrial activation patterns. Attempts at establishing the presence of a ‘lower common pathway’ are probably of no practical significance. When the diagnosis of AVNRT is established, ablation should be only directed towards the anatomic position of the slow pathway. If right septal attempts are unsuccessful, the left septal side should be tried. Ablation targeting earliest atrial activation sites during typical atrioventricular nodal reentrant tachycardia or the fast pathway in general for any kind of typical or atypical atrioventricular nodal reentrant tachycardia, are not justified. In this review we discuss current concepts about the tachycardia circuit, electrophysiologic diagnosis, and ablation of this arrhythmia. PMID:27617092

  15. Classification, Electrophysiological Features and Therapy of Atrioventricular Nodal Reentrant Tachycardia

    PubMed Central

    Josephson, Mark E

    2016-01-01

    Atrioventricular nodal reentrant tachycardia (AVNRT) should be classified as typical or atypical. The term ‘fast-slow AVNRT’ is rather misleading. Retrograde atrial activation during tachycardia should not be relied upon as a diagnostic criterion. Both typical and atypical atrioventricular nodal reentrant tachycardia are compatible with varying retrograde atrial activation patterns. Attempts at establishing the presence of a ‘lower common pathway’ are probably of no practical significance. When the diagnosis of AVNRT is established, ablation should be only directed towards the anatomic position of the slow pathway. If right septal attempts are unsuccessful, the left septal side should be tried. Ablation targeting earliest atrial activation sites during typical atrioventricular nodal reentrant tachycardia or the fast pathway in general for any kind of typical or atypical atrioventricular nodal reentrant tachycardia, are not justified. In this review we discuss current concepts about the tachycardia circuit, electrophysiologic diagnosis, and ablation of this arrhythmia.

  16. Generation of functional thyroid from embryonic stem cells.

    PubMed

    Antonica, Francesco; Kasprzyk, Dominika Figini; Opitz, Robert; Iacovino, Michelina; Liao, Xiao-Hui; Dumitrescu, Alexandra Mihaela; Refetoff, Samuel; Peremans, Kathelijne; Manto, Mario; Kyba, Michael; Costagliola, Sabine

    2012-11-01

    The primary function of the thyroid gland is to metabolize iodide by synthesizing thyroid hormones, which are critical regulators of growth, development and metabolism in almost all tissues. So far, research on thyroid morphogenesis has been missing an efficient stem-cell model system that allows for the in vitro recapitulation of the molecular and morphogenic events regulating thyroid follicular-cell differentiation and subsequent assembly into functional thyroid follicles. Here we report that a transient overexpression of the transcription factors NKX2-1 and PAX8 is sufficient to direct mouse embryonic stem-cell differentiation into thyroid follicular cells that organize into three-dimensional follicular structures when treated with thyrotropin. These in vitro-derived follicles showed appreciable iodide organification activity. Importantly, when grafted in vivo into athyroid mice, these follicles rescued thyroid hormone plasma levels and promoted subsequent symptomatic recovery. Thus, mouse embryonic stem cells can be induced to differentiate into thyroid follicular cells in vitro and generate functional thyroid tissue.

  17. Genetic analysis of the roles of Hh, FGF8, and nodal signaling during catecholaminergic system development in the zebrafish brain.

    PubMed

    Holzschuh, Jochen; Hauptmann, Giselbert; Driever, Wolfgang

    2003-07-01

    CNS catecholaminergic neurons can be distinguished by their neurotransmitters as dopaminergic or noradrenergic and form in distinct regions at characteristic embryonic stages. This raises the question of whether all catecholaminergic neurons of one transmitter type are specified by the same set of factors. Therefore, we performed genetic analyses to define signaling requirements for the specification of distinct clusters of catecholaminergic neurons in zebrafish. In mutants affecting midbrain- hindbrain boundary (MHB) organizer formation, the earliest ventral diencephalic dopaminergic neurons appear normal. However, after 2 d of development, we observed fewer cells than in wild types, which suggests that the MHB provides proliferation or survival factors rather than specifying ventral diencephalic dopaminergic clusters. In hedgehog (Hh) pathway mutants, the formation of catecholaminergic neurons is affected only in the pretectal cluster. Surprisingly, neither fibroblast growth factor 8 (FGF8) alone nor in combination with Hh signaling is required for specification of early developing dopaminergic neurons. We analyzed the formation of prosomeric territories in the forebrain of Hh and Nodal pathway mutants to determine whether the absence of specific dopaminergic clusters may be caused by early patterning defects ablating corresponding parts of the CNS. In Nodal pathway mutants, ventral diencephalic and pretectal catecholaminergic neurons fail to develop, whereas both anatomical structures form at least in part. This suggests that Nodal signaling is required for catecholaminergic neuron specification. In summary, our results do not support the previously suggested dominant roles for sonic hedgehog and Fgf8 in specification of the first catecholaminergic neurons, but instead indicate a novel role for Nodal signaling in this process. PMID:12843251

  18. Bilinear nodal transport method in weighted diamond difference form

    SciTech Connect

    Azmy, Y.Y.

    1987-01-01

    Nodal methods have been developed and implemented for the numerical solution of the discrete ordinates neutron transport equation. Numerical testing of these methods and comparison of their results to those obtained by conventional methods have established the high accuracy of nodal methods. Furthermore, it has been suggested that the linear-linear approximation is the most computationally efficient, practical nodal approximation. Indeed, this claim has been substantiated by comparing the accuracy in the solution, and the CPU time required to achieve convergence to that solution by several nodal approximations, as well as the diamond difference scheme. Two types of linear-linear nodal methods have been developed in the literature: analytic linear-linear (NLL) methods, in which the transverse-leakage terms are derived analytically, and approximate linear-linear (PLL) methods, in which these terms are approximated. In spite of their higher accuracy, NLL methods result in very complicated discrete-variable equations that exhibit a high degree of coupling, thus requiring special solution algorithms. On the other hand, the sacrificed accuracy in PLL methods is compensated for by the simple discrete-variable equations and diamond-difference-like solution algorithm. In this paper the authors outline the development of an NLL nodal method, the bilinear method, which can be written in a weighted diamond difference form with one spatial weight per dimension that is analytically derived rather than preassigned in an ad hoc fashion.

  19. An upwind nodal integral method for incompressible fluid flow

    SciTech Connect

    Esser, P.D. ); Witt, R.J. )

    1993-05-01

    An upwind nodal solution method is developed for the steady, two-dimensional flow of an incompressible fluid. The formulation is based on the nodal integral method, which uses transverse integrations, analytical solutions of the one-dimensional averaged equations, and node-averaged uniqueness constraints to derive the discretized nodal equations. The derivation introduces an exponential upwind bias by retaining the streamwise convection term in the homogeneous part of the transverse-integrated convection-diffusion equation. The method is adapted to the stream function-vorticity form of the Navier-Stokes equations, which are solved over a nonstaggered nodal mesh. A special nodal scheme is used for the Poisson stream function equation to properly account for the exponentially varying vorticity source. Rigorous expressions for the velocity components and the no-slip vorticity boundary condition are derived from the stream function formulation. The method is validated with several benchmark problems. An idealized purely convective flow of a scalar step function indicates that the nodal approximation errors are primarily dispersive, not dissipative, in nature. Results for idealized and actual recirculating driven-cavity flows reveal a significant reduction in false diffusion compared with conventional finite difference techniques.

  20. Short-range signaling by candidate morphogens of the TGF beta family and evidence for a relay mechanism of induction.

    PubMed

    Reilly, K M; Melton, D A

    1996-09-01

    The specification and patterning of cell fates by a morphogen gradient is a unifying theme of developmental biology, yet little evidence exists for the presence of gradients in vivo or to show how such putative gradients form. Vg1 and activin are candidate morphogens involved in Xenopus mesoderm induction. This study suggests that these TGF beta family members act on adjacent cells but do not travel through the intact extracellular space to induce distant cells directly. Moreover, we present evidence for the presence of secondary inducing signals that could be involved in relaying signals to distant cells. These results suggest that if a localized cellular source of an inducer acts to pattern mesodermal cells at a distance in Xenopus embryos, it does so by a relay mechanism.

  1. Modeling digits. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients.

    PubMed

    Raspopovic, J; Marcon, L; Russo, L; Sharpe, J

    2014-08-01

    During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation. PMID:25082703

  2. Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction

    PubMed Central

    Minuth, Will W.; Denk, Lucia

    2016-01-01

    Abstract Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of specimens by glutaraldehyde (GA) solution including cupromeronic blue, ruthenium red, or tannic acid for electron microscopy depicts that the interface is not void but filled in extended areas by textured extracellular matrix. Surprisingly, projections of mesenchymal cells cross the interface to contact epithelial cells. At those sites the plasma membranes of a mesenchymal and an epithelial cell are connected via tunneling nanotubes. Regarding detected morphological features in combination with involved morphogens, their transport cannot longer be explained solely by diffusion. Instead, it has to be sorted according to biophysical properties of morphogens and to detected environment. Thus, the new working hypothesis is that morphogens with good solubility such as glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factors (FGFs) are transported by diffusion. Morphogens with minor solubility such as bone morphogenetic proteins (BMPs) are secreted and stored for delivery on demand in illustrated extracellular matrix. In contrast, morphogens with poor solubility such as Wnts are transported in mesenchymal cell projections along the plasma membrane or via illustrated tunneling nanotubes. However, the presence of an intercellular route between mesenchymal and epithelial stem/progenitor cells by tunneling nanotubes also makes it possible that all morphogens are transported this way. PMID:26862472

  3. miRNA-mediated feedback inhibition of JAK/STAT morphogen signalling establishes a cell fate threshold.

    PubMed

    Yoon, Wan Hee; Meinhardt, Hans; Montell, Denise J

    2011-09-01

    Patterns of cell fates generated by morphogens are critically important for normal development; however, the mechanisms by which graded morphogen signals are converted into all-or-none cell fate responses are incompletely understood. In the Drosophila ovary, high and sustained levels of the secreted morphogen Unpaired (Upd) specify the migratory border-cell population by activating the signal transducer and activator of transcription (STAT). A lower or transient level of STAT activity specifies a non-migratory population of follicle cells. Here we identify miR-279 as a component of a feedback pathway that further dampens the response in cells with low levels of JAK/STAT activity. miR-279 directly repressed STAT, and loss of miR-279 mimicked STAT gain-of-function or loss of Apontic (Apt), a known feedback inhibitor of STAT. Apt was essential for miR-279 expression in non-migratory follicle cells, whereas another STAT target, Ken and Barbie (Ken), downregulated miR-279 in border cells. Mathematical modelling and simulations of this regulatory circuit including miR-279, Apt and Ken supported key roles for miR-279 and Apt in generating threshold responses to the Upd gradient. PMID:21857668

  4. Millennium recurrence interval of morphogenic earthquakes on the Qingchuan fault, northeastern segment of the Longmen Shan Thrust Belt, China

    NASA Astrophysics Data System (ADS)

    Lin, Aiming; Yan, Bing; Rao, Gang

    2016-04-01

    The 2008 M w 7.9 Wenchuan produced a ˜285-300-km-long coseismic surface rupture zone, including a 60-km-long segment along the Qingchuan fault, the northeastern segment of the Longmen Shan Thrust Belt (LSTB), Sichuan Basin, central China. Field investigations, trench excavations, and radiocarbon dating results reveal that (i) the Qingchuan fault is currently active as a seismogenic fault, along which four morphogenic earthquakes including the 2008 Wenchuan earthquake occurred in the past ca. 3500 years, suggesting an average millennium recurrence interval of morphogenic earthquakes in the late Holocene; (ii) the most recent event prior to the 2008 Wenchuan earthquake took place in the period between AD 1400 and AD 1100; (iii) the penultimate paleoseismic event occurred in the period around 2000 years BP in the Han Dynasty (206 BC-AD 220); (iv) the third paleoseismic event occurred in the period between 900 and 1800 BC; and (v) at least three seismic faulting events occurred in the early Holocene. The present results are comparable with those inferred in the central and southwestern segments of the LSTB within which the Wenchuan magnitude earthquakes occurred in a millennium recurrence interval, that are in contrast with previous estimates of 2000-10,000 years for the recurrence interval of morphogenic earthquakes within the LSTB and thereby necessitating substantial modifications to existing seismic hazard models for the densely populated region at the Sichuan region.

  5. A BMP-FGF morphogen toggle switch drives the ultrasensitive expression of multiple genes in the developing forebrain.

    PubMed

    Srinivasan, Shyam; Hu, Jia Sheng; Currle, D Spencer; Fung, Ernest S; Hayes, Wayne B; Lander, Arthur D; Monuki, Edwin S

    2014-02-01

    Borders are important as they demarcate developing tissue into distinct functional units. A key challenge is the discovery of mechanisms that can convert morphogen gradients into tissue borders. While mechanisms that produce ultrasensitive cellular responses provide a solution, how extracellular morphogens drive such mechanisms remains poorly understood. Here, we show how Bone Morphogenetic Protein (BMP) and Fibroblast Growth Factor (FGF) pathways interact to generate ultrasensitivity and borders in the dorsal telencephalon. BMP and FGF signaling manipulations in explants produced border defects suggestive of cross inhibition within single cells, which was confirmed in dissociated cultures. Using mathematical modeling, we designed experiments that ruled out alternative cross inhibition mechanisms and identified a cross-inhibitory positive feedback (CIPF) mechanism, or "toggle switch", which acts upstream of transcriptional targets in dorsal telencephalic cells. CIPF explained several cellular phenomena important for border formation such as threshold tuning, ultrasensitivity, and hysteresis. CIPF explicitly links graded morphogen signaling in the telencephalon to switch-like cellular responses and has the ability to form multiple borders and scale pattern to size. These benefits may apply to other developmental systems. PMID:24550718

  6. A BMP-FGF Morphogen Toggle Switch Drives the Ultrasensitive Expression of Multiple Genes in the Developing Forebrain

    PubMed Central

    Currle, D. Spencer; Fung, Ernest S.; Hayes, Wayne B.; Lander, Arthur D.; Monuki, Edwin S.

    2014-01-01

    Borders are important as they demarcate developing tissue into distinct functional units. A key challenge is the discovery of mechanisms that can convert morphogen gradients into tissue borders. While mechanisms that produce ultrasensitive cellular responses provide a solution, how extracellular morphogens drive such mechanisms remains poorly understood. Here, we show how Bone Morphogenetic Protein (BMP) and Fibroblast Growth Factor (FGF) pathways interact to generate ultrasensitivity and borders in the dorsal telencephalon. BMP and FGF signaling manipulations in explants produced border defects suggestive of cross inhibition within single cells, which was confirmed in dissociated cultures. Using mathematical modeling, we designed experiments that ruled out alternative cross inhibition mechanisms and identified a cross-inhibitory positive feedback (CIPF) mechanism, or “toggle switch”, which acts upstream of transcriptional targets in dorsal telencephalic cells. CIPF explained several cellular phenomena important for border formation such as threshold tuning, ultrasensitivity, and hysteresis. CIPF explicitly links graded morphogen signaling in the telencephalon to switch-like cellular responses and has the ability to form multiple borders and scale pattern to size. These benefits may apply to other developmental systems. PMID:24550718

  7. [MORPHOMETRIC AND HISTOCHEMICAL CHARACTERISTICS OF THE THYROID GLAND AFTER ADMINISTRATION OF HYDRA PEPTIDE MORPHOGEN].

    PubMed

    Kulayeva, V V; Bykov, V L

    2016-01-01

    The effect of Hydra peptide morphogen (HPM) on quantitative histochemical and morphometric parameters of the thyroid gland (TG) was studied. The experiments were conducted on 40 outbred albino male mice weighing 20-25 g, which were injected intraperitoneally with HPM at the dose of 100 μg/kg of body weight per day for 5 days. Relative volumes occupied by the epithelium (E), including its follicular (E(f)), interfollicular (E(i)) components, and colloid (C) were determined using stereological method on TG transverse sections. E(f)/E(i) and E/C ratios were calculated as the indices of follicular organization and TG activity, respectively. Mitotic activity of thyrocytes was also evaluated. The enzymes, characterizing the metabolic activity of thyrocytes: NADH-diaphorase, succinate- and lactate dehydrogenases were demonstrated on cryostat sections of material, frozen in liquid nitrogen and their activity was assessed cytophotometrically. The results demonstrated that HPM administration lead to a significant increase in relative volume of thyroid epithelium with a concomitant reduction of the volume of the colloid. E(f)/E(i) ratio was not significantly different from that in the control. HPM also induced a significant increase of thyrocyte proliferation rate and of the activity of enzymes studied. Collectively, the quantitative histoenzymological and morphometric data obtained indicate the stimulating effect of HPM on TG functional activity and thyrocyte proliferation.

  8. High glucose and palmitate increases bone morphogenic protein 4 expression in human endothelial cells

    PubMed Central

    Hong, Oak-Kee; Yoo, Soon-Jib; Son, Jang-Won; Kim, Mee-Kyoung; Baek, Ki-Hyun; Song, Ki-Ho; Cha, Bong-Yun; Jo, Hanjoong

    2016-01-01

    Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL. PMID:26937213

  9. The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice.

    PubMed

    Koga, Mitsuhisa; Engberding, Niels; Dikalova, Anna E; Chang, Kyung Hwa; Seidel-Rogol, Bonnie; Long, James S; Lassègue, Bernard; Jo, Hanjoong; Griendling, Kathy K

    2013-09-01

    Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease. PMID:23812391

  10. [MORPHOMETRIC AND HISTOCHEMICAL CHARACTERISTICS OF THE THYROID GLAND AFTER ADMINISTRATION OF HYDRA PEPTIDE MORPHOGEN].

    PubMed

    Kulayeva, V V; Bykov, V L

    2016-01-01

    The effect of Hydra peptide morphogen (HPM) on quantitative histochemical and morphometric parameters of the thyroid gland (TG) was studied. The experiments were conducted on 40 outbred albino male mice weighing 20-25 g, which were injected intraperitoneally with HPM at the dose of 100 μg/kg of body weight per day for 5 days. Relative volumes occupied by the epithelium (E), including its follicular (E(f)), interfollicular (E(i)) components, and colloid (C) were determined using stereological method on TG transverse sections. E(f)/E(i) and E/C ratios were calculated as the indices of follicular organization and TG activity, respectively. Mitotic activity of thyrocytes was also evaluated. The enzymes, characterizing the metabolic activity of thyrocytes: NADH-diaphorase, succinate- and lactate dehydrogenases were demonstrated on cryostat sections of material, frozen in liquid nitrogen and their activity was assessed cytophotometrically. The results demonstrated that HPM administration lead to a significant increase in relative volume of thyroid epithelium with a concomitant reduction of the volume of the colloid. E(f)/E(i) ratio was not significantly different from that in the control. HPM also induced a significant increase of thyrocyte proliferation rate and of the activity of enzymes studied. Collectively, the quantitative histoenzymological and morphometric data obtained indicate the stimulating effect of HPM on TG functional activity and thyrocyte proliferation. PMID:27487666

  11. Morphogenic and biochemical variations under different spectral lights in callus cultures of Artemisia absinthium L.

    PubMed

    Tariq, Umayya; Ali, Mohammad; Abbasi, Bilal Haider

    2014-01-01

    Through its impact on morphogenesis, light is the key environmental factor that alters plant architectural development; however, the understanding that how light controls plant growth and developmental processes is still poor and needs further research. In this study, we monitored the effect of various monochromatic lights and plant growth regulators (PGRs) combinations on morphogenic and biochemical variation in wild grown-leaf derived callus cultures of Artemisia absinthium L. Combination of α-naphthalene acetic acid (NAA 1.0mg/l) and Thidiazuron (TDZ 2.0mg/l) resulted in optimum callogenic frequency (90%) when kept under fluorescent light for 4weeks (16/8h). In contrast to the control (white spectrum), red spectrum enhanced peroxidase activity, protease activity, total protein content and chlorophyll a/b ratio. Green spectrum was found to be more supportive for total phenolics, total flavonoids and antioxidant activity. Yellow light enhanced MDA content while white and green light improved total chlorophyll content and carotenoid content. A positive correlation among callogenic response, antioxidant activities and set of antioxidative enzyme activities was also observed in the current report. This study will help in understanding the influence of light on production of commercially important secondary metabolites and their optimization in the in vitro cultures of A. absinthium L.

  12. Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration.

    PubMed

    Rolland-Lagan, Anne-Gaëlle; Paquette, Mathieu; Tweedle, Valerie; Akimenko, Marie-Andrée

    2012-03-01

    The fact that some organisms are able to regenerate organs of the correct shape and size following amputation is particularly fascinating, but the mechanism by which this occurs remains poorly understood. The zebrafish (Danio rerio) caudal fin has emerged as a model system for the study of bone development and regeneration. The fin comprises 16 to 18 bony rays, each containing multiple joints along its proximodistal axis that give rise to segments. Experimental observations on fin ray growth, regeneration and joint formation have been described, but no unified theory has yet been put forward to explain how growth and joint patterns are controlled. We present a model for the control of fin ray growth during development and regeneration, integrated with a model for joint pattern formation, which is in agreement with published, as well as new, experimental data. We propose that fin ray growth and joint patterning are coordinated through the interaction of three morphogens. When the model is extended to incorporate multiple rays across the fin, it also accounts for how the caudal fin acquires its shape during development, and regains its correct size and shape following amputation. PMID:22318227

  13. Morphogenic Protein RodZ Interacts with Sporulation Specific SpoIIE in Bacillus subtilis

    PubMed Central

    Muchová, Katarína; Chromiková, Zuzana; Bradshaw, Niels; Wilkinson, Anthony J.

    2016-01-01

    The first landmark in sporulation of Bacillus subtilis is the formation of an asymmetric septum followed by selective activation of the transcription factor σF in the resulting smaller cell. How the morphological transformations that occur during sporulation are coupled to cell-specific activation of transcription is largely unknown. The membrane protein SpoIIE is a constituent of the asymmetric sporulation septum and is a crucial determinant of σF activation. Here we report that the morphogenic protein, RodZ, which is essential for cell shape determination, is additionally required for asymmetric septum formation and sporulation. In cells depleted of RodZ, formation of asymmetric septa is disturbed and σF activation is perturbed. During sporulation, we found that SpoIIE recruits RodZ to the asymmetric septum. Moreover, we detected a direct interaction between SpoIIE and RodZ in vitro and in vivo, indicating that SpoIIE-RodZ may form a complex to coordinate asymmetric septum formation and σF activation. We propose that RodZ could provide a link between the cell shape machinery and the coordinated morphological and developmental transitions required to form a resistant spore. PMID:27415800

  14. Arsenic-induced morphogenic response in roots of arsenic hyperaccumulator fern Pteris vittata.

    PubMed

    Forino, Laura Maria Costantina; Ruffini Castiglione, Monica; Bartoli, Giacomo; Balestri, Mirko; Andreucci, Andrea; Tagliasacchi, Anna Maria

    2012-10-15

    On the assumption that arsenic induces stress morphogenetic responses involved in As tolerance and hyperaccumulation in the Pteris vittata fern, we analyzed the root system of young sporophytes grown in 250, 334, and 500 μM As for five days and for 14 days. Anatomical and histological analyses were performed in plants grown for five days to evaluate the number, position, length and differentiation pattern of root hairs. AgNOR staining, employed to study nucleolus behavior in root apices, showed that arsenic influences nucleolar activity (evaluated by nucleolus size, number and absorbance) in the root meristem. In plants treated with 250 and 334 μM As an acropetal shift of root hair development and an increase in hair length and density were observed, linked to an ectopic pattern of differentiation. The opposite trend was recorded in plants treated with 500 μM As. It is worth noting the presence of living border-like cells, not yet observed in ferns, and their increase following As treatments. Analysis and vitality of border-like cells were surveyed after 14 days of treatments. In conclusion As treatments elicited a stress-induced morphogenic response which, by modifying the differentiation pattern, number and length of root hairs, modulating nucleolar activity and interacting with the rhizosphere by inducing border-like cell production, may adjust the rate of root uptake and its metabolic activity.

  15. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

    NASA Technical Reports Server (NTRS)

    Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert; Jo, Hanjoong

    2003-01-01

    Atherosclerosis is now viewed as an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions, including oscillatory shear stress (OS), in branched arteries. In contrast, the arterial regions exposed to laminar shear (LS) are relatively lesion-free. The mechanisms underlying the opposite effects of OS and LS on the inflammatory and atherogenic processes are not clearly understood. Here, through DNA microarrays, protein expression, and functional studies, we identify bone morphogenic protein 4 (BMP4) as a mechanosensitive and pro-inflammatory gene product. Exposing endothelial cells to OS increased BMP4 protein expression, whereas LS decreased it. In addition, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. The same endothelial patches also expressed higher levels of intercellular cell adhesion molecule-1 (ICAM-1) protein compared with those of non-diseased areas. Functionally, we show that OS and BMP4 induced ICAM-1 expression and monocyte adhesion by a NFkappaB-dependent mechanism. We suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in the lesion-prone areas.

  16. Functional dissection and evidence for intercellular transfer of the heterocyst-differentiation PatS morphogen.

    PubMed

    Corrales-Guerrero, Laura; Mariscal, Vicente; Flores, Enrique; Herrero, Antonia

    2013-06-01

    The formation of a diazotrophic cyanobacterial filament represents a simple example of biological development. In Anabaena, a non-random pattern of one nitrogen-fixing heterocyst separated by about 10 photosynthetic vegetative cells results from lateral inhibition elicited by the cells differentiating into heterocysts. Key to this process is the patS gene, which has been shown to produce an inhibitor of heterocyst differentiation that involves the C-terminal RGSGR pentapeptide. Complementation of a ΔpatS Anabaena mutant with different versions of PatS, including point mutations or tag fusions, showed that patS is translated into a 17-amino acid polypeptide. Alterations in the N-terminal part of PatS produced inhibition of heterocyst differentiation, thus this part of the peptide appears necessary for proper processing and self-immunity in the producing cells. Alterations in the C-terminal part of PatS led to over-differentiation, thus supporting its role in inhibition of heterocyst differentiation. A polypeptide, produced in proheterocysts, consisting of a methionine followed by the eight, but not the five, terminal amino acids of PatS recreated the full activity of the native peptide. Immunofluorescence detection showed that an RGSGR-containing peptide accumulated in the cells adjacent to the producing proheterocysts, illustrating intercellular transfer of a morphogen in the cyanobacterial filaments. PMID:23663167

  17. High glucose and palmitate increases bone morphogenic protein 4 expression in human endothelial cells.

    PubMed

    Hong, Oak-Kee; Yoo, Soon-Jib; Son, Jang-Won; Kim, Mee-Kyoung; Baek, Ki-Hyun; Song, Ki-Ho; Cha, Bong-Yun; Jo, Hanjoong; Kwon, Hyuk-Sang

    2016-03-01

    Here, we investigated whether hyperglycemia and/or free fatty acids (palmitate, PAL) aff ect the expression level of bone morphogenic protein 4 (BMP4), a proatherogenic marker, in endothelial cells and the potential role of BMP4 in diabetic vascular complications. To measure BMP4 expression, human umbilical vein endothelial cells (HUVECs) were exposed to high glucose concentrations and/or PAL for 24 or 72 h, and the effects of these treatments on the expression levels of adhesion molecules and reactive oxygen species (ROS) were examined. BMP4 loss-of-function status was achieved via transfection of a BMP4-specific siRNA. High glucose levels increased BMP4 expression in HUVECs in a dose-dependent manner. PAL potentiated such expression. The levels of adhesion molecules and ROS production increased upon treatment with high glucose and/or PAL, but this eff ect was negated when BMP4 was knocked down via siRNA. Signaling of BMP4, a proinflammatory and pro-atherogenic cytokine marker, was increased by hyperglycemia and PAL. BMP4 induced the expression of infl ammatory adhesion molecules and ROS production. Our work suggests that BMP4 plays a role in atherogenesis induced by high glucose levels and/or PAL. PMID:26937213

  18. Sexually dimorphic regulation of the Wingless morphogen controls sex-specific segment number in Drosophila

    PubMed Central

    Wang, Wei; Kidd, Bryan J.; Carroll, Sean B.; Yoder, John H.

    2011-01-01

    Sexual dimorphism is widespread throughout the metazoa and plays important roles in mate recognition and preference, sex-based niche partitioning, and sex-specific coadaptation. One notable example of sex-specific differences in insect body morphology is presented by the higher diptera, such as Drosophila, in which males develop fewer abdominal segments than females. Because diversity in segment number is a distinguishing feature of major arthropod clades, it is of fundamental interest to understand how different numbers of segments can be generated within the same species. Here we show that sex-specific and segment-specific regulation of the Wingless (Wg) morphogen underlies the development of sexually dimorphic adult segment number in Drosophila. Wg expression is repressed in the developing terminal male abdominal segment by the combination of the Hox protein Abdominal-B (Abd-B) and the sex-determination regulator Doublesex (Dsx). The subsequent loss of the terminal male abdominal segment during pupation occurs through a combination of developmental processes including segment compartmental transformation, apoptosis, and suppression of cell proliferation. Furthermore, we show that ectopic expression of Wg is sufficient to rescue this loss. We propose that dimorphic Wg regulation, in concert with monomorphic segment-specific programmed cell death, are the principal mechanisms of sculpting the sexually dimorphic abdomen of Drosophila. PMID:21690416

  19. Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics

    NASA Astrophysics Data System (ADS)

    Lucchetta, Elena M.; Lee, Ji Hwan; Fu, Lydia A.; Patel, Nipam H.; Ismagilov, Rustem F.

    2005-04-01

    Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions-a temperature step-in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development.

  20. Development of depletion perturbation theory for a reactor nodal code

    SciTech Connect

    Bowman, S.M.

    1981-09-01

    A generalized depletion perturbation (DPT) theory formulation for light water reactor (LWR) depletion problems is developed and implemented into the three-dimensional LWR nodal code SIMULATE. This development applies the principles of the original derivation by M.L. Williams to the nodal equations solved by SIMULATE. The present formulation is first described in detail, and the nodal coupling methodology in SIMULATE is used to determine partial derivatives of the coupling coefficients. The modifications to the original code and the new DPT options available to the user are discussed. Finally, the accuracy and the applicability of the new DPT capability to LWR design analysis are examined for several LWR depletion test cases. The cases range from simple static cases to a realistic PWR model for an entire fuel cycle. Responses of interest included K/sub eff/, nodal peaking, and peak nodal exposure. The nonlinear behavior of responses with respect to perturbations of the various types of cross sections was also investigated. The time-dependence of the sensitivity coefficients for different responses was examined and compared. Comparison of DPT results for these examples to direct calculations reveals the limited applicability of depletion perturbation theory to LWR design calculations at the present. The reasons for these restrictions are discussed, and several methods which might improve the computational accuracy of DPT are proposed for future research.

  1. On the Nodal Lines of Eisenstein Series on Schottky Surfaces

    NASA Astrophysics Data System (ADS)

    Jakobson, Dmitry; Naud, Frédéric

    2016-09-01

    On convex co-compact hyperbolic surfaces {X=Γ backslash H2} , we investigate the behavior of nodal curves of real valued Eisenstein series {F_λ(z,ξ)} , where {λ} is the spectral parameter, {ξ} the direction at infinity. Eisenstein series are (non-{L^2} ) eigenfunctions of the Laplacian {Δ_X} satisfying {Δ_X F_λ=(1/4+λ^2)F_λ} . As {λ} goes to infinity (the high energy limit), we show that, for generic {ξ} , the number of intersections of nodal lines with any compact segment of geodesic grows like {λ} , up to multiplicative constants. Applications to the number of nodal domains inside the convex core of the surface are then derived.

  2. Simulating Weyl points and nodal loops in an optical superlattice

    NASA Astrophysics Data System (ADS)

    Zhang, Dan-Wei

    2016-08-01

    We propose a scheme to simulate Weyl points and nodal loops with ultracold atoms in an optical lattice that is subjected to realizable synthetic magnetic field and synthetic dimension. We show that a Hofstadter-like Hamiltonian with a cyclically parameterized on-site energy term can be realized in a tunable two-dimensional optical superlattice, based on the laser-assisted atomic tunneling method. This model effectively describes a three-dimensional periodic lattice system under magnetic fluxes, where a synthetic dimension is encoded by a cyclical phase of the optical lattice potential. For different atomic hopping configurations, the single-particle bands are demonstrated to, respectively, exhibit Weyl points and nodal loops in the extended three-dimensional Brillouin zone. Furthermore, we illustrate that the mimicked Weyl points and nodal loops can be experimentally detected by measuring the atomic transfer fraction in Bloch-Zener oscillations.

  3. Three-dimensional transport with variational nodal methods

    SciTech Connect

    Lewis, E.E.; Palmiotti, G.; Shalil, H.S.; Laurin-Kovitz, K.; Fanning, T.; Hanebutte, U.R.

    1996-12-31

    The development of the variational nodal method contained in the three-dimensional transport code VARIANT is reviewed. This Argonne National Laboratory code treats two- and three- dimensional multigroup problems with anisotropic scattering in hexagonal and Cartesian geometries. The methodology couples hybrid finite elements in space, which enforce nodal balance, with spherical harmonics expansions in angle. The resulting response matrix equations are solved by red-black or four-color iterations. Several enhancements to VARIANT are discussed: The simplified spherical harmonics option provides near spherical harmonic accuracy for many problems at a fraction of the cost. Adjoint and perturbation calculations are performed without the physical- and mathematical adjoint dichotomy appearing in other nodal methods. Heterogeneous node methods extend the problem classes to which the method may be applied. Computational strategies and trade-offs are discussed and possible future research directions are outlined.

  4. A computational study of nodal-based tetrahedral element behavior.

    SciTech Connect

    Gullerud, Arne S.

    2010-09-01

    This report explores the behavior of nodal-based tetrahedral elements on six sample problems, and compares their solution to that of a corresponding hexahedral mesh. The problems demonstrate that while certain aspects of the solution field for the nodal-based tetrahedrons provide good quality results, the pressure field tends to be of poor quality. Results appear to be strongly affected by the connectivity of the tetrahedral elements. Simulations that rely on the pressure field, such as those which use material models that are dependent on the pressure (e.g. equation-of-state models), can generate erroneous results. Remeshing can also be strongly affected by these issues. The nodal-based test elements as they currently stand need to be used with caution to ensure that their numerical deficiencies do not adversely affect critical values of interest.

  5. Super-nodal methods for space-time kinetics

    NASA Astrophysics Data System (ADS)

    Mertyurek, Ugur

    The purpose of this research has been to develop an advanced Super-Nodal method to reduce the run time of 3-D core neutronics models, such as in the NESTLE reactor core simulator and FORMOSA nuclear fuel management optimization codes. Computational performance of the neutronics model is increased by reducing the number of spatial nodes used in the core modeling. However, as the number of spatial nodes decreases, the error in the solution increases. The Super-Nodal method reduces the error associated with the use of coarse nodes in the analyses by providing a new set of cross sections and ADFs (Assembly Discontinuity Factors) for the new nodalization. These so called homogenization parameters are obtained by employing consistent collapsing technique. During this research a new type of singularity, namely "fundamental mode singularity", is addressed in the ANM (Analytical Nodal Method) solution. The "Coordinate Shifting" approach is developed as a method to address this singularity. Also, the "Buckling Shifting" approach is developed as an alternative and more accurate method to address the zero buckling singularity, which is a more common and well known singularity problem in the ANM solution. In the course of addressing the treatment of these singularities, an effort was made to provide better and more robust results from the Super-Nodal method by developing several new methods for determining the transverse leakage and collapsed diffusion coefficient, which generally are the two main approximations in the ANM methodology. Unfortunately, the proposed new transverse leakage and diffusion coefficient approximations failed to provide a consistent improvement to the current methodology. However, improvement in the Super-Nodal solution is achieved by updating the homogenization parameters at several time points during a transient. The update is achieved by employing a refinement technique similar to pin-power reconstruction. A simple error analysis based on the relative

  6. Deformation modes in the finite element absolute nodal coordinate formulation

    NASA Astrophysics Data System (ADS)

    Sugiyama, Hiroyuki; Gerstmayr, Johannes; Shabana, Ahmed A.

    2006-12-01

    The objective of this study is to provide interpretation of the deformation modes in the finite element absolute nodal coordinate formulation using several strain definitions. In this finite element formulation, the nodal coordinates consist of absolute position coordinates and gradients that can be used to define a unique rotation and deformation fields within the element as well as at the nodal points. The results obtained in this study clearly show cross-section deformation modes eliminated when the number of the finite element nodal coordinates is systematically and consistently reduced. Using the procedure discussed in this paper one can obtain a reduced order dynamic model, eliminate position vector gradients that introduce high frequencies to the solution of some problems, achieve the continuity of the remaining gradients at the nodal points, and obtain a formulation that automatically satisfies the principle of work and energy. Furthermore, the resulting dynamic model, unlike large rotation finite element formulations, leads to a unique rotation field, and as a consequence, the obtained formulation does not suffer from the problem of coordinate redundancy that characterizes existing large deformation finite element formulations. In order to accurately define strain components that can have easy physical interpretation, a material coordinate system is introduced to define the material element rotation and deformation. Using the material coordinate system, the Timoshenko-Reissner and Euler -Bernoulli beam models can be systematically obtained as special cases of the absolute nodal coordinate formulation beam models. While a constraint approach is used in this study to eliminate the cross-section deformation modes, it is important to point out as mentioned in this paper that lower-order finite elements, some of which already presented in previous investigations, can be efficiently used in thin and stiff structure applications.

  7. A transient, quadratic nodal method for triangular-Z geometry

    SciTech Connect

    DeLorey, T.F.

    1993-06-01

    Many systematically-derived nodal methods have been developed for Cartesian geometry due to the extensive interest in Light Water Reactors. These methods typically model the transverse-integrated flux as either an analytic or low order polynomial function of position within the node. Recently, quadratic nodal methods have been developed for R-Z and hexagonal geometry. A static and transient quadratic nodal method is developed for triangular-Z geometry. This development is particularly challenging because the quadratic expansion in each node must be performed between the node faces and the triangular points. As a consequence, in the 2-D plane, the flux and current at the points of the triangles must be treated. Quadratic nodal equations are solved using a non-linear iteration scheme, which utilizes the corrected, mesh-centered finite difference equations, and forces these equations to match the quadratic equations by computing discontinuity factors during the solution. Transient nodal equations are solved using the improved quasi-static method, which has been shown to be a very efficient solution method for transient problems. Several static problems are used to compare the quadratic nodal method to the Coarse Mesh Finite Difference (CMFD) method. The quadratic method is shown to give more accurate node-averaged fluxes. However, it appears that the method has difficulty predicting node leakages near reactor boundaries and severe material interfaces. The consequence is that the eigenvalue may be poorly predicted for certain reactor configurations. The transient methods are tested using a simple analytic test problem, a heterogeneous heavy water reactor benchmark problem, and three thermal hydraulic test problems. Results indicate that the transient methods have been implemented correctly.

  8. Embryonal cancers in Europe.

    PubMed

    Gatta, Gemma; Ferrari, Andrea; Stiller, Charles A; Pastore, Guido; Bisogno, Gianni; Trama, Annalisa; Capocaccia, Riccardo

    2012-07-01

    Embryonal cancers are a heterogeneous group of rare cancers which mainly occur in children and adolescents. The aim of the present study was to estimate the burden (incidence, prevalence, survival and proportion of cured) for the principal embryonal cancers in Europe (EU27), using population-based data from cancer registries (CRs) participating in RARECARE. We identified 3322 cases diagnosed from 1995 to 2002 (latest period for which data are available): 44% neuroblastoma, 35% nephroblastoma, 13% retinoblastoma and 6% hepatoblastoma. Very few cases of pulmonary blastoma (43 cases) and pancreatoblastoma (seven cases) were diagnosed. About 2000 new embryonal cancers were estimated every year in EU27, for an annual incidence rate of 4 per million (1.8 neuroblastoma, 1.4 nephroblastoma, and 0.5 retinoblastoma); 91% of cases occurred in patients under 15 years. Five-year relative survival for all embryonal cancers was 80% (99% retinoblastoma, 90% nephroblastoma, 71% hepatoblastoma and 68% neuroblastoma). Overall survival was lower in adolescents and adults than in those under 15 years. The cure rate was estimated at 80%. Slightly less than 40,000 persons were estimated alive in EU27 with a diagnosis of embryonal cancer in 2008. Nephroblastoma was the most prevalent (18,150 cases in EU27), followed by neuroblastoma (12,100), retinoblastoma (5200), hepatoblastoma (2700) and pulmonary blastoma (614). This is the first study to delineate the embryonal cancer burden in Europe by age, sex and European region. Survival/cure rate is generally high, but there are considerable gaps in our understanding of the natural histories of these rare diseases particularly in adults.

  9. Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 in Vivo

    PubMed Central

    Dorai, Thambi; Diouri, Janane; O'Shea, Orla; Doty, Stephen B.

    2014-01-01

    A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-β signaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP- 7). This enhancement of BMP-7 in the context of TGF-βin the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regu- lated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-βsignaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic

  10. Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 in Vivo.

    PubMed

    Dorai, Thambi; Diouri, Janane; O'Shea, Orla; Doty, Stephen B

    2014-04-01

    A number of studies have focused on the beneficial properties of Curcumin (diferuloyl methane, used in South Asian cuisine and traditional medicine) such as the chemoprevention of cancer. Recent studies have also indicated that this material has significant benefits for the treatment of cancer and is currently undergoing several clinical trials. We have been interested in the application of this compound as a therapeutic agent for advanced prostate cancer, particularly the skeletal complications in this malignancy. Our earlier work indicated that this compound could inhibit the osteomimetic properties which occur in castration resistant prostate cancer cells, by interfering with the common denominators between these cancer cells and the bone cells in the metastatic tumor microenvironment, namely the osteoblasts and the osteoclast. We predicted that curcumin could break the vicious cycle of reciprocal stimulation that results in uncontrolled osteolysis in the bony matrix. In this work, we have evaluated the potential of this compound in inhibiting the bone metastasis of hormone refractory prostate cancer cells in an established animal model. Our results strongly suggest that curcumin modulates the TGF-β signaling that occurs due to bone matrix degradation by up-regulating the metastasis inhibitory bone morphogenic protein-7 (BMP- 7). This enhancement of BMP-7 in the context of TGF-βin the tumor microenvironment is shown to enhance the mesenchymal-to-epithelial transition. Most importantly, we show that as a result of BMP-7 up-regulation, a novel brown/beige adipogenic differentiation program is also up-regu- lated which plays a role in the inhibition of bone metastasis. Our results suggest that curcumin may subvert the TGF-βsignaling to an alternative adipogenic differentiation program in addition to the previously established interference with the osteomimetic properties, thus inhibiting the bone metastatic processes in a chemopreventive as well as therapeutic

  11. Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry.

    PubMed

    Maerten, Clément; Garnier, Tony; Lupattelli, Paolo; Chau, Nguyet Trang Thanh; Schaaf, Pierre; Jierry, Loïc; Boulmedais, Fouzia

    2015-12-15

    Inspired by the strong chemical adhesion mechanism of mussels, we designed a catechol-based electrochemically triggered self-assembly of films based on ethylene glycol molecules bearing catechol groups on both sides and denoted as bis-catechol molecules. These molecules play the role of morphogens and, in contrast to previously investigated systems, they are also one of the constituents, after reaction, of the film. Unable to interact together, commercially available poly(allylamine hydrochloride) (PAH) chains and bis-catechol molecules are mixed in an aqueous solution and brought in contact with an electrode. By application of defined potential cycles, bis-catechol molecules undergo oxidation leading to molecules bearing "reactive" quinone groups which diffuse toward the solution. In this active state, the quinones react with amino groups of PAH through Michael addition and Schiff's base condensation reaction. The application of cyclic voltammetry (CV) between 0 and 500 mV (vs Ag/AgCl, scan rate of 50 mV/s) of a PAH/bis-catechol solution results in a fast self-construction of a film that reaches a thickness of 40 nm after 60 min. The films present a spiky structure which is attributed to the use of bis-functionalized molecules as one component of the films. XPS measurements show the presence of both PAH and bis-catechol cross-linked together in a covalent way. We show that the amine/catechol ratio is an important parameter which governs the film buildup. For a given amine/catechol ratio, it does exist an optimum CV scan rate leading to a maximum of the film thickness as a function of the scan rate. PMID:26575431

  12. Public awareness of the bone morphogenic protein controversy: Evidence from news publications

    PubMed Central

    Drazin, Doniel; Shweikeh, Faris; Wieshofer, Erich; Kim, Terrence T.; Johnson, J. Patrick

    2014-01-01

    Background: Use of recombinant human bone morphogenic protein-2 (rhBMP-2) in spinal fusion has seen a tremendous increase. Public awareness of rhBMP-2 and its complications has not been assessed. The authors studied published news media articles to analyze information provided to the public on this bone graft substitute. Methods: We utilized the academic database, LexisNexis, to locate newspaper articles published between January 2001 and July 2013. All articles were coded by a coder and reviewed by the principal investigator. Results: The search identified 87 national and 99 local newspaper articles. Complications mentioned in national newspapers included cancer (24%), retrograde ejaculation (24%), and abnormal bone growth (14%). Local newspapers cited cancer (14%), inflammation (14%), and retrograde ejaculation (9.2%) most frequently. Fifty national (59%) and 35 local (54%) articles had no mention of complications. Sources of evidence cited by articles were (in order of frequency): Governmental agencies, medical research or published studies, healthcare personnel or patients, and companies or corporations. Conclusions: Only a small percentage of newspaper articles presented potential complications. Despite lack of clear scientific causal relationship between rhBMP-2 and cancer, this risk was disproportionately reported. Additionally, many did not cite scientific sources. Lack of reliable information available to the public reiterates the role of physicians in discussing risks and benefits BMP use in spinal surgery, assuring that patients are making informed decisions. Future news media articles should present risks in an impartial and evidence-based manner. Collaboration between advocacy groups, medical institutions, and media outlets would be beneficial in achieving this goal. PMID:25593772

  13. Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry.

    PubMed

    Maerten, Clément; Garnier, Tony; Lupattelli, Paolo; Chau, Nguyet Trang Thanh; Schaaf, Pierre; Jierry, Loïc; Boulmedais, Fouzia

    2015-12-15

    Inspired by the strong chemical adhesion mechanism of mussels, we designed a catechol-based electrochemically triggered self-assembly of films based on ethylene glycol molecules bearing catechol groups on both sides and denoted as bis-catechol molecules. These molecules play the role of morphogens and, in contrast to previously investigated systems, they are also one of the constituents, after reaction, of the film. Unable to interact together, commercially available poly(allylamine hydrochloride) (PAH) chains and bis-catechol molecules are mixed in an aqueous solution and brought in contact with an electrode. By application of defined potential cycles, bis-catechol molecules undergo oxidation leading to molecules bearing "reactive" quinone groups which diffuse toward the solution. In this active state, the quinones react with amino groups of PAH through Michael addition and Schiff's base condensation reaction. The application of cyclic voltammetry (CV) between 0 and 500 mV (vs Ag/AgCl, scan rate of 50 mV/s) of a PAH/bis-catechol solution results in a fast self-construction of a film that reaches a thickness of 40 nm after 60 min. The films present a spiky structure which is attributed to the use of bis-functionalized molecules as one component of the films. XPS measurements show the presence of both PAH and bis-catechol cross-linked together in a covalent way. We show that the amine/catechol ratio is an important parameter which governs the film buildup. For a given amine/catechol ratio, it does exist an optimum CV scan rate leading to a maximum of the film thickness as a function of the scan rate.

  14. Variational nodal solution algorithms for multigroup criticality problems

    SciTech Connect

    Carrico, C.B.; Lewis, E.E.

    1991-01-01

    Variational nodal transport methods are generalized for the treatment of multigroup criticality problems. The generation of variational response matrices is streamlined and automated through the use of symbolic manipulation. A new red-black partitioned matrix algorithm for the solution of the within-group equations is formulated and shown to be at once both a regular matrix splitting and a synthetic acceleration method. The methods are implemented in X- Y geometry as a module of the Argonne National Laboratory code DIF3D. For few group problems highly accurate P[sub 3] eigenvalues are obtained with computing times comparable to those of an existing interface-current nodal transport method.

  15. Long period nodal motion of sun synchronous orbits

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1975-01-01

    An approximative model is formulated for assessing these perturbations that significantly affect long term modal motion of sun synchronous orbits. Computer simulations with several independent computer programs consider zonal and tesseral gravitational harmonics, third body gravitational disturbances induced by the sun and the moon, and atmospheric drag. A pendulum model consisting of evenzonal harmonics through order 4 and solar gravity dominated nodal motion approximation. This pendulum motion results from solar gravity inducing an inclination oscillation which couples into the nodal precession induced by the earth's oblateness. The pendulum model correlated well with simulations observed flight data.

  16. Chiral Spin-Orbital Liquids with Nodal Lines

    NASA Astrophysics Data System (ADS)

    Natori, W. M. H.; Andrade, E. C.; Miranda, E.; Pereira, R. G.

    2016-07-01

    Strongly correlated materials with strong spin-orbit coupling hold promise for realizing topological phases with fractionalized excitations. Here, we propose a chiral spin-orbital liquid as a stable phase of a realistic model for heavy-element double perovskites. This spin liquid state has Majorana fermion excitations with a gapless spectrum characterized by nodal lines along the edges of the Brillouin zone. We show that the nodal lines are topological defects of a non-Abelian Berry connection and that the system exhibits dispersing surface states. We discuss some experimental signatures of this state and compare them with properties of the spin liquid candidate Ba2YMoO6.

  17. Comparative role of phosphotyrosine kinase domains of c-ros and c-ret protooncogenes in metanephric development with respect to growth factors and matrix morphogens.

    PubMed

    Liu, Z Z; Wada, J; Kumar, A; Carone, F A; Takahashi, M; Kanwar, Y S

    1996-08-25

    Receptor-like protooncogenes, with tyrosine kinase catalytic domains, are expressed in neoplastic and fetal tissues and potentially have a role in embryonic development. Which protooncogene may have the dominant role in embryonic renal development during the "postinductive" period, i.e., Day 10 onward, was addressed in this study by utilizing an in vitro organ culture system. The role of various receptor-like protooncogenes, with the emphasis on c-ros and c-ret, was investigated by antisense-oligodeoxynucleotide (ODN) gene-targeting strategies at a point in metanephric development when reciprocal-inductive interactions between the epithelium and mesenchyme have already been initiated and are rampant. Also, their relationship with other morphogens, like extracellular matrix (ECM) proteins and growth factors, was studied. Initial in situ hybridization and RT-PCR analyses revealed a similar spatiotemporal expression for both c-ros and c-ret in the embryonic kidneys. At Day 13, they were mainly expressed in the developing nephrons in the nephrogenic zone and ureteric bud branches, where the signals from the mesenchymal ligands are transduced to the epithelial cell surface receptors. Minimal expression was observed in the newborn kidneys. Inclusion of antisense ODNs, derived from the phosphotyrosine kinase domains, inhibited metanephric growth in the organ culture; the most dramatic effects were observed with the c-ret antisense ODN. The c-ret-induced dysmorphogenetic effects were characterized as a decrease in the population of nephrons, atrophy of the mesenchymal cells, and loss of acuteness of the tips of ureteric bud branches. Interestingly, the ureteric bud branches continue to grow in the atrophic mesenchyme. Both c-ros and c-ret antisense ODNs reduced the gene expression and biosynthesis of various ECM proteins. The proteoglycans, expressed at the epithelial:mesenchymal interface, were most adversely affected, especially by the c-ret antisense. The treatment of

  18. A transient, Hex-Z nodal code corrected by discontinuity factors. Volume 1: The transient nodal code; Final report

    SciTech Connect

    Shatilla, Y.A.M.; Henry, A.F.

    1993-12-31

    This document constitutes Volume 1 of the Final Report of a three-year study supported by the special Research Grant Program for Nuclear Energy Research set up by the US Department of Energy. The original motivation for the work was to provide a fast and accurate computer program for the analysis of transients in heavy water or graphite-moderated reactors being considered as candidates for the New Production Reactor. Thus, part of the funding was by way of pass-through money from the Savannah River Laboratory. With this intent in mind, a three-dimensional (Hex-Z), general-energy-group transient, nodal code was created, programmed, and tested. In order to improve accuracy, correction terms, called {open_quotes}discontinuity factors,{close_quotes} were incorporated into the nodal equations. Ideal values of these factors force the nodal equations to provide node-integrated reaction rates and leakage rates across nodal surfaces that match exactly those edited from a more exact reference calculation. Since the exact reference solution is needed to compute the ideal discontinuity factors, the fact that they result in exact nodal equations would be of little practical interest were it not that approximate discontinuity factors, found at a greatly reduced cost, often yield very accurate results. For example, for light-water reactors, discontinuity factors found from two-dimensional, fine-mesh, multigroup transport solutions for two-dimensional cuts of a fuel assembly provide very accurate predictions of three-dimensional, full-core power distributions. The present document (volume 1) deals primarily with the specification, programming and testing of the three-dimensional, Hex-Z computer program. The program solves both the static (eigenvalue) and transient, general-energy-group, nodal equations corrected by user-supplied discontinuity factors.

  19. Extension of the linear nodal method to large concrete building calculations

    SciTech Connect

    Childs, R.L.; Rhoades, W.A.

    1985-01-01

    The implementation of the linear nodal method in the TORT code is described, and the results of a mesh refinement study to test the effectiveness of the linear nodal and weighted diamond difference methods available in TORT are presented.

  20. Millennium recurrence interval of morphogenic earthquakes on the Qingchuan fault, northeastern segment of the Longmen Shan Thrust Belt, China

    NASA Astrophysics Data System (ADS)

    Lin, A.

    2015-12-01

    In this study, I present new paleoseismic and topographic evidence for the Holocene faulting activity, including the recurrence interval of morphogenic earthquakes and the slip rate along the Qingchuan fault, the northern segment of the Longmen Shan Thrust Belt, central China, and discuss its tectonic implications for the zone at the eastern margin of the Tibetan Plateau. Field investigations, trench excavations, and radiocarbon dating results reveal that: (i) the Qingchuan fault is currently active as a seismogenic fault, along which six morphogenic earthquakes occurred in the past 6000 years; (ii) the most recent event prior to the 2008 Wenchuan earthquake took place in the period between AD 600 and 1400, which probably corresponds to the late Tang-Song (AD 800-1000) (M~8) earthquake that occurred in the central and southwestern segments of the LSTB; (iii) the penultimate paleoseismic event occurred in the period around 2000 yr BP, suggesting a millennium recurrence interval of morphogenic earthquakes in the late Holocene. The present results are comparable with those inferred in the central and southwestern segments of the LSTB within which the Wenchuan-magnitude earthquakes occurred in a millennium recurrence interval, that are in contrast with previous estimates of 2000-10,000 years for the recurrence interval of morphogenic earthquakes within the LSTB, and thereby necessitating substantial modifications to exiting seismic-hazard models for the densely populated region at the Sichuan region. References: 1) Lin, A., Rao, G., and Yan, B., 2012. Field evidence of rupture of the Qingchuan Fault during the 2008 Mw7.9 Wenchuan earthquake, northeastern segment of the Longmen Shan Thrust Belt, China. Tectonophysics, 522-523, 243-252, doi:10.1016/j.tecto.2011.12.012 2) Lin, A., Rao, G., and Yan, B., 2014. Structural analysis of the right-lateral strike-slip Qingchuan fault, northeastern segment of the Longmen Shan thrust belt, central China. Journal of Structural

  1. Nodal Structure and the Partitioning of Equivalence Classes

    ERIC Educational Resources Information Center

    Fields, Lanny; Watanabe-Rose, Mari

    2008-01-01

    By definition, all of the stimuli in an equivalence class have to be functionally interchangeable with each other. The present experiment, however, demonstrated that this was not the case when using post-class-formation dual-option response transfer tests. With college students, two 4-node 6-member equivalence classes with nodal structures of…

  2. PoroTomo Subtask 6.3 Nodal Seismometers Metadata

    DOE Data Explorer

    Lesley Parker

    2016-03-28

    Metadata for the nodal seismometer array deployed at the POROTOMO's Natural Laboratory in Brady Hot Spring, Nevada during the March 2016 testing. Metadata includes location and timing for each instrument as well as file lists of data to be uploaded in a separate submission.

  3. Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro.

    PubMed

    Zhou, Quan; Wang, Mei; Yuan, Yan; Wang, Xuepeng; Fu, Rui; Wan, Haifeng; Xie, Mingming; Liu, Mingxi; Guo, Xuejiang; Zheng, Ying; Feng, Guihai; Shi, Qinghua; Zhao, Xiao-Yang; Sha, Jiahao; Zhou, Qi

    2016-03-01

    In vitro generation of functional gametes is a promising approach for treating infertility, although faithful replication of meiosis has proven to be a substantial obstacle to deriving haploid gamete cells in culture. Here we report complete in vitro meiosis from embryonic stem cell (ESC)-derived primordial germ cells (PGCLCs). Co-culture of PGCLCs with neonatal testicular somatic cells and sequential exposure to morphogens and sex hormones reproduced key hallmarks of meiosis, including erasure of genetic imprinting, chromosomal synapsis and recombination, and correct nuclear DNA and chromosomal content in the resulting haploid cells. Intracytoplasmic injection of the resulting spermatid-like cells into oocytes produced viable and fertile offspring, showing that this robust stepwise approach can functionally recapitulate male gametogenesis in vitro. These findings provide a platform for investigating meiotic mechanisms and the potential generation of human haploid spermatids in vitro.

  4. 3D reconstitution of the patterned neural tube from embryonic stem cells.

    PubMed

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

    2014-12-01

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

  5. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Digital Electronic Message Service Nodal... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may...

  6. Organoids and the genetically encoded self‐assembly of embryonic stem cells

    PubMed Central

    Baillie‐Johnson, Peter

    2015-01-01

    Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. PMID:26666846

  7. Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

    PubMed

    Redies, Christoph; Neudert, Franziska; Lin, Juntang

    2011-09-01

    Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

  8. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

    SciTech Connect

    Simian, M.; Harail, Y.; Navre, M.; Werb, Z.; Lochter, A.; Bissell, M.J.

    2002-03-06

    The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP-3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a critical role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

  9. Wave pinning and spatial patterning in a mathematical model of Antivin/Lefty-Nodal signalling.

    PubMed

    Middleton, A M; King, J R; Loose, M

    2013-12-01

    Nodal signals are key regulators of mesoderm and endoderm development in vertebrate embryos. It has been observed experimentally that in Xenopus embryos the spatial range of Nodal signals is restricted by the signal Antivin (also known as Lefty). Nodal signals can activate both Nodal and Antivin, whereas Antivin is thought to antagonise Nodal by binding either directly to it or to its receptor. In this paper we develop a mathematical model of this signalling network in a line of cells. We consider the heterodimer and receptor-mediated inhibition mechanisms separately and find that, in both cases, the restriction by Antivin to the range of Nodal signals corresponds to wave pinning in the model. Our analysis indicates that, provided Antivin diffuses faster than Nodal, either mechanism can robustly account for the experimental data. We argue that, in the case of Xenopus development, it is wave pinning, rather than Turing-type patterning, that is underlying Nodal-Antivin dynamics. This leads to several experimentally testable predictions, which are discussed. Furthermore, for heterodimer-mediated inhibition to prevent waves of Nodal expression from propagating, the Nodal-Antivin complex must be turned over, and diffusivity of the complex must be negligible. In the absence of molecular mechanisms regulating these, we suggest that Antivin restricts Nodal signals via receptor-mediated, and not heterodimer-mediated, inhibition. PMID:23070212

  10. Chiral Spin-Orbital Liquids with Nodal Lines.

    PubMed

    Natori, W M H; Andrade, E C; Miranda, E; Pereira, R G

    2016-07-01

    Strongly correlated materials with strong spin-orbit coupling hold promise for realizing topological phases with fractionalized excitations. Here, we propose a chiral spin-orbital liquid as a stable phase of a realistic model for heavy-element double perovskites. This spin liquid state has Majorana fermion excitations with a gapless spectrum characterized by nodal lines along the edges of the Brillouin zone. We show that the nodal lines are topological defects of a non-Abelian Berry connection and that the system exhibits dispersing surface states. We discuss some experimental signatures of this state and compare them with properties of the spin liquid candidate Ba_{2}YMoO_{6}. PMID:27419588

  11. Off-diagonal Jacobian support for Nodal BCs

    SciTech Connect

    Peterson, John W.; Andrs, David; Gaston, Derek R.; Permann, Cody J.; Slaughter, Andrew E.

    2015-01-01

    In this brief note, we describe the implementation of o-diagonal Jacobian computations for nodal boundary conditions in the Multiphysics Object Oriented Simulation Environment (MOOSE) [1] framework. There are presently a number of applications [2{5] based on the MOOSE framework that solve complicated physical systems of partial dierential equations whose boundary conditions are often highly nonlinear. Accurately computing the on- and o-diagonal Jacobian and preconditioner entries associated to these constraints is crucial for enabling ecient numerical solvers in these applications. Two key ingredients are required for properly specifying the Jacobian contributions of nonlinear nodal boundary conditions in MOOSE and nite element codes in general: 1. The ability to zero out entire Jacobian matrix rows after \

  12. Anomalous contagion and renormalization in networks with nodal mobility

    NASA Astrophysics Data System (ADS)

    Manrique, Pedro D.; Qi, Hong; Zheng, Minzhang; Xu, Chen; Hui, Pak Ming; Johnson, Neil F.

    2016-07-01

    A common occurrence in everyday human activity is where people join, leave and possibly rejoin clusters of other individuals —whether this be online (e.g. social media communities) or in real space (e.g. popular meeting places such as cafes). In the steady state, the resulting interaction network would appear static over time if the identities of the nodes are ignored. Here we show that even in this static steady-state limit, a non-zero nodal mobility leads to a diverse set of outbreak profiles that is dramatically different from known forms, and yet matches well with recent real-world social outbreaks. We show how this complication of nodal mobility can be renormalized away for a particular class of networks.

  13. Anomalous thermodynamic power laws near topological transitions in nodal superconductors

    NASA Astrophysics Data System (ADS)

    Mazidian, B.; Quintanilla, J.; Hillier, A. D.; Annett, J. F.

    2013-12-01

    Unconventional superconductors are most frequently identified by the observation of power-law behavior on low-temperature thermodynamic or transport properties, such as specific heat. Here, we show that, in addition to the usual point and line nodes, a much wider class of different nodal types can occur. These new types of nodes typically occur when there are transitions between different types of gap node topology, for example, when point or line nodes first appear as a function of some physical parameter. We identify anomalous, noninteger thermodynamic power laws associated with these new nodal types, and give physical examples of superconductors in which they might be observed experimentally, including the noncentrosymmetric superconductor Li2Pd3-xPtxB.

  14. Nodal failure index approach to groundwater remediation design

    USGS Publications Warehouse

    Lee, J.; Reeves, H.W.; Dowding, C.H.

    2008-01-01

    Computer simulations often are used to design and to optimize groundwater remediation systems. We present a new computationally efficient approach that calculates the reliability of remedial design at every location in a model domain with a single simulation. The estimated reliability and other model information are used to select a best remedial option for given site conditions, conceptual model, and available data. To evaluate design performance, we introduce the nodal failure index (NFI) to determine the number of nodal locations at which the probability of success is below the design requirement. The strength of the NFI approach is that selected areas of interest can be specified for analysis and the best remedial design determined for this target region. An example application of the NFI approach using a hypothetical model shows how the spatial distribution of reliability can be used for a decision support system in groundwater remediation design. ?? 2008 ASCE.

  15. Atrioventricular nodal reentrant tachycardia ablation and inferior vena cava agenesis.

    PubMed

    Galand, Vincent; Pavin, Dominique; Behar, Nathalie; Mabo, Philippe; Martins, Raphaël P

    2016-10-01

    Congenital anomalies of the inferior vena cava (IVC) are rare and very often diagnosed in asymptomatic patients during computed tomography performed for other purposes. These anomalies can have significant clinical implications, for example if electrophysiology procedures are needed. Diagnostic and ablation procedures are difficult since catheter manipulation and positioning are more complex. We present here a case of successful atrioventricular nodal reentrant tachycardia ablation in a patient with unexpected IVC agenesis, using an azygos route. PMID:27633734

  16. Nodal equivalence theory for hexagonal geometry, thermal reactor analysis

    SciTech Connect

    Zika, M.; Downar, T. )

    1992-01-01

    An important aspect of advanced nodal methods is the determination of equivalent few-group parameters for the relatively large homogenized regions used in the nodal flux solution. The theoretical foundation for light water reactor (LWR) assembly homogenization methods has been clearly established, and during the last several years, its successes have secured its position in the stable of dependable LWR analysis methods. Groupwise discontinuity factors that correct for assembly homogenization errors are routinely generated along with the group constants during lattice physics analysis. During the last several years, there has been interest in applying equivalence theory to other reactor types and other geometries. A notable effort has been the work at Argonne National Laboratory to incorporate nodal equivalence theory (NET) for hexagonal lattices into the nodal diffusion option of the DIF3D code. This work was originally intended to improve the neutronics methods used for the analysis of the Experimental Breeder Reactor II (EBR-II), and Ref. 4 discusses the success of that application. More recently, however, attempts were made to apply NET to advanced, thermal reactor designs such as the modular high-temperature gas reactor (MHTGR) and the new production heavy water reactor (NPR/HWR). The same methods that were successful for EBR-II have encountered problems for these reactors. Our preliminary analysis indicates that the sharp global flux gradients in these cores requires large discontinuity factors (greater than 4 or 5) to reproduce the reference solution. This disrupts the convergence of the iterative methods used to solve for the node-wise flux moments and partial currents. Several attempts to remedy the problem have been made over the last few years, including bounding the discontinuity factors and providing improved initial guesses for the flux solution, but nothing has been satisfactory.

  17. Nodal Basin Recurrence After Sentinel Lymph Node Biopsy for Melanoma

    PubMed Central

    Kretschmer, Lutz; Bertsch, Hans Peter; Zapf, Antonia; Mitteldorf, Christina; Satzger, Imke; Thoms, Kai-Martin; Völker, Bernward; Schön, Michael Peter; Gutzmer, Ralf; Starz, Hans

    2015-01-01

    Abstract The objective of this study was to analyze different types of nodal basin recurrence after sentinel lymph node biopsy (SLNB) for melanoma. Patients and Methods: Kaplan–Meier estimates and the Cox proportional hazards model were used to study 2653 patients from 3 German melanoma centers retrospectively. The estimated 5-year negative predictive value of SLNB was 96.4%. The estimated false-negative (FN) rates after 1, 2, 3, 5, and 10 years were 2.5%, 4.6%, 6.4%, 8.7%, and 12.6%, respectively. Independent factors associated with false negativity were older age, fewer SLNs excised, and head or neck location of the primary tumor. Compared with SLN-positive patients, the FNs had a significantly lower survival. In SLN-positive patients undergoing completion lymphadenectomy (CLND), the 5-year nodal basin recurrence rate was 18.3%. The recurrence rates for axilla, groin, and neck were 17.2%, 15.5%, and 44.1%, respectively. Significant factors predicting local relapse after CLND were older age, head, or neck location of the primary tumor, ulceration, deeper penetration of the metastasis into the SLN, tumor-positive CLND, and >2 lymph node metastases. All kinds of nodal relapse were associated with a higher prevalence of in-transit metastases. The FN rate after SLNB steadily increases over the observation period and should, therefore, be estimated by the Kaplan–Meier method. False-negativity is associated with fewer SLNs excised. The beneficial effect of CLND on nodal basin disease control varies considerably across different risk groups. This should be kept in mind about SLN-positive patients when individual decisions on prophylactic CLND are taken. PMID:26356697

  18. Progress and applications of the variational nodal method

    SciTech Connect

    Carrico, C.B.; Palmiotti, G.; Lewis, E.E.

    1995-07-01

    This paper summarizes current progress and developments with the variational nodal method(VNM) and its implementaion within the DIF3D code suite. After a brief development of the mathematical basis for the VNM, results from two three-dimensional benchmarks are presented for a variety of computers. Then current applications of the VNM are discussed including diffusion theory calculations, burnup calculations, highly heterogeneous cores, higher-order spherical harmonics approximations, perturbation theory and heterogeneous nodes.

  19. Topological Phase Transitions in Line-nodal Superconductors

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Han, Sangeun; Moon, Eun-Gook

    Fathoming interplay between symmetry and topology of many-electron wave-functions deepens our understanding in quantum nature of many particle systems. Topology often protects zero-energy excitation, and in a certain class, symmetry is intrinsically tied to the topological protection. Namely, unless symmetry is broken, topological nature is intact. We study one specific case of such class, symmetry-protected line-nodal superconductors in three spatial dimensions (3d). Mismatch between phase spaces of order parameter fluctuation and line-nodal fermion excitation induces an exotic universality class in a drastic contrast to one of the conventional ϕ4 theory in 3d. Hyper-scaling violation and relativistic dynamic scaling with unusually large quantum critical region are main characteristics, and their implication in experiments is discussed. For example, continuous phase transition out of line-nodal superconductors has a linear phase boundary in a temperature-tuning parameter phase-diagram. This work was supported by the Brain Korea 21 PLUS Project of Korea Government and KAIST start-up funding.

  20. Anomalous scaling of the penetration depth in nodal superconductors

    NASA Astrophysics Data System (ADS)

    She, Jian-Huang; Lawler, Michael J.; Kim, Eun-Ah

    2015-07-01

    Recent findings of anomalous superlinear scaling of low-temperature (T ) penetration depth (PD) in several nodal superconductors near putative quantum critical points suggest that the low-temperature PD can be a useful probe of quantum critical fluctuations in a superconductor. On the other hand, cuprates, which are poster child nodal superconductors, have not shown any such anomalous scaling of PD, despite growing evidence of quantum critical points (QCP). Then it is natural to ask when and how can quantum critical fluctuations cause anomalous scaling of PD? Carrying out the renormalization group calculation for the problem of two-dimensional superconductors with point nodes, we show that quantum critical fluctuations associated with a point group symmetry reduction result in nonuniversal logarithmic corrections to the T dependence of the PD. The resulting apparent power law depends on the bare velocity anisotropy ratio. We then compare our results to data sets from two distinct nodal superconductors: YBa2Cu3O6.95 and CeCoIn5. Considering all symmetry-lowering possibilities of the point group of interest, C4 v, we find our results to be remarkably consistent with YBa2Cu3O6.95 being near a vertical nematic QCP and CeCoIn5 being near a diagonal nematic QCP. Our results motivate a search for diagonal nematic fluctuations in CeCoIn5.

  1. LSST Telescope Alignment Plan Based on Nodal Aberration Theory

    NASA Astrophysics Data System (ADS)

    Sebag, J.; Gressler, W.; Schmid, T.; Rolland, J. P.; Thompson, K. P.

    2012-04-01

    The optical alignment of the Large Synoptic Survey Telescope (LSST) is potentially challenging, due to its fast three-mirror optical design and its large 3.5° field of view (FOV). It is highly advantageous to align the three-mirror optical system prior to the integration of the complex science camera on the telescope, which corrects the FOV via three refractive elements and includes the operational wavefront sensors. A telescope alignment method based on nodal aberration theory (NAT) is presented here to address this challenge. Without the science camera installed on the telescope, the on-axis imaging performance of the telescope is diffraction-limited, but the field of view is not corrected. The nodal properties of the three-mirror telescope design have been analyzed and an alignment approach has been developed using the intrinsically linear nodal behavior, which is linked via sensitivities to the misalignment parameters. Since mirror figure errors will exist in any real application, a methodology to introduce primary-mirror figure errors into the analysis has been developed and is also presented.

  2. A nodal domain theorem for integrable billiards in two dimensions

    SciTech Connect

    Samajdar, Rhine; Jain, Sudhir R.

    2014-12-15

    Eigenfunctions of integrable planar billiards are studied — in particular, the number of nodal domains, ν of the eigenfunctions with Dirichlet boundary conditions are considered. The billiards for which the time-independent Schrödinger equation (Helmholtz equation) is separable admit trivial expressions for the number of domains. Here, we discover that for all separable and non-separable integrable billiards, ν satisfies certain difference equations. This has been possible because the eigenfunctions can be classified in families labelled by the same value of mmodkn, given a particular k, for a set of quantum numbers, m,n. Further, we observe that the patterns in a family are similar and the algebraic representation of the geometrical nodal patterns is found. Instances of this representation are explained in detail to understand the beauty of the patterns. This paper therefore presents a mathematical connection between integrable systems and difference equations. - Highlights: • We find that the number of nodal domains of eigenfunctions of integrable, planar billiards satisfy a class of difference equations. • The eigenfunctions labelled by quantum numbers (m,n) can be classified in terms of mmodkn. • A theorem is presented, realising algebraic representations of geometrical patterns exhibited by the domains. • This work presents a connection between integrable systems and difference equations.

  3. Reduced NODAL signaling strength via mutation of several pathway members including FOXH1 is linked to human heart defects and holoprosencephaly.

    PubMed

    Roessler, Erich; Ouspenskaia, Maia V; Karkera, Jayaprakash D; Vélez, Jorge I; Kantipong, Amy; Lacbawan, Felicitas; Bowers, Peter; Belmont, John W; Towbin, Jeffrey A; Goldmuntz, Elizabeth; Feldman, Benjamin; Muenke, Maximilian

    2008-07-01

    Abnormalities of embryonic patterning are hypothesized to underlie many common congenital malformations in humans including congenital heart defects (CHDs), left-right disturbances (L-R) or laterality, and holoprosencephaly (HPE). Studies in model organisms suggest that Nodal-like factors provide instructions for key aspects of body axis and germ layer patterning; however, the complex genetics of pathogenic gene variant(s) in humans are poorly understood. Here we report our studies of FOXH1, CFC1, and SMAD2 and summarize our mutational analysis of three additional components in the human NODAL-signaling pathway: NODAL, GDF1, and TDGF1. We identify functionally abnormal gene products throughout the pathway that are clearly associated with CHD, laterality, and HPE. Abnormal gene products are most commonly detected in patients within a narrow spectrum of isolated conotruncal heart defects (minimum 5%-10% of subjects), and far less commonly in isolated laterality or HPE patients (approximately 1% for each). The difference in the mutation incidence between these groups is highly significant. We show that apparent gene dosage discrepancies between humans and model organisms can be reconciled by considering a broader combination of sequence variants. Our studies confirm that (1) the genetic vulnerabilities inferred from model organisms with defects in Nodal signaling are indeed analogous to humans; (2) the molecular analysis of an entire signaling pathway is more complete and robust than that of individual genes and presages future studies by whole-genome analysis; and (3) a functional genomics approach is essential to fully appreciate the complex genetic interactions necessary to produce these effects in humans.

  4. [Teratogenesis and gene targets of 17alpha-ethynylestradiol on embryonic development in zebrafish].

    PubMed

    Tong, Jun-Wei; Zhang, Jing-Pu; Meng, Jie

    2011-01-01

    The pharmaceutical ethynylestradiol (EE) is a potent endocrine modulator. Application enlargement of ethynylestradiol in clinics and abuse in livestock farming and fishing make it important to explore ethynylestradiol toxicological action on vertebrate embryonic development and to establish an in vivo method for EE toxicity detection efficiently and conveniently. In the present study, using a model animal zebrafish and 17alpha-ethynylestradiol as a representative compound, we have investigated EE2 teratogenicity, target tissues and target genes on zebrafish embryo. The results show that median teratogenesis concentration (TC50) of EE2 is 0.8 microg x mL(-1), and median lethal dose (LD50) is 3.3 microg x mL(-1). Targets of EE2 action were implicated in brain, eyes, heart, muscle, skeleton, pigment and viscera. Embryonic cardiac arrhythmia caused by EE2 is probably resulted from heart abnormal structure. The embryonic stage sensitive to EE2 mainly started at cleavage and last up to the organogenesis with time-accumulating effect. RT-PCR results indicate that EE2 treatment disturbed gene expression pattern at the early period of zebrafish embryonic development by suppressing transcription of gene boz that promotes brain development, upregulating genes for trunk and tail, such as ntl, spt, shh, and perturbing Nodal signal expression of TGFbeta superfamily, for example, cyc, sqt and oep. Using zebrafish, an efficient in vivo method for quick evaluation of EE toxicity on embryonic development has been developed.

  5. Apoplastic reactive oxygen species transiently decrease auxin signaling and cause stress-induced morphogenic response in Arabidopsis.

    PubMed

    Blomster, Tiina; Salojärvi, Jarkko; Sipari, Nina; Brosché, Mikael; Ahlfors, Reetta; Keinänen, Markku; Overmyer, Kirk; Kangasjärvi, Jaakko

    2011-12-01

    Reactive oxygen species (ROS) are ubiquitous signaling molecules in plant stress and development. To gain further insight into the plant transcriptional response to apoplastic ROS, the phytotoxic atmospheric pollutant ozone was used as a model ROS inducer in Arabidopsis (Arabidopsis thaliana) and gene expression was analyzed with microarrays. In contrast to the increase in signaling via the stress hormones salicylic acid, abscisic acid, jasmonic acid (JA), and ethylene, ROS treatment caused auxin signaling to be transiently suppressed, which was confirmed with a DR5-uidA auxin reporter construct. Transcriptomic data revealed that various aspects of auxin homeostasis and signaling were modified by apoplastic ROS. Furthermore, a detailed analysis of auxin signaling showed that transcripts of several auxin receptors and Auxin/Indole-3-Acetic Acid (Aux/IAA) transcriptional repressors were reduced in response to apoplastic ROS. The ROS-derived changes in the expression of auxin signaling genes partially overlapped with abiotic stress, pathogen responses, and salicylic acid signaling. Several mechanisms known to suppress auxin signaling during biotic stress were excluded, indicating that ROS regulated auxin responses via a novel mechanism. Using mutants defective in various auxin (axr1, nit1, aux1, tir1 afb2, iaa28-1, iaa28-2) and JA (axr1, coi1-16) responses, ROS-induced cell death was found to be regulated by JA but not by auxin. Chronic ROS treatment resulted in altered leaf morphology, a stress response known as "stress-induced morphogenic response." Altered leaf shape of tir1 afb2 suggests that auxin was a negative regulator of stress-induced morphogenic response in the rosette.

  6. Response of millet and sorghum to a varying water supply around the primary and nodal roots

    PubMed Central

    Rostamza, M.; Richards, R. A.; Watt, M.

    2013-01-01

    Background and Aims Cereals have two root systems. The primary system originates from the embryo when the seed germinates and can support the plant until it produces grain. The nodal system can emerge from stem nodes throughout the plant's life; its value for yield is unclear and depends on the environment. The aim of this study was to test the role of nodal roots of sorghum and millet in plant growth in response to variation in soil moisture. Sorghum and millet were chosen as both are adapted to dry conditions. Methods Sorghum and millet were grown in a split-pot system that allowed the primary and nodal roots to be watered separately. Key Results When primary and nodal roots were watered (12 % soil water content; SWC), millet nodal roots were seven times longer than those of sorghum and six times longer than millet plants in dry treatments, mainly from an 8-fold increase in branch root length. When soil was allowed to dry in both compartments, millet nodal roots responded and grew 20 % longer branch roots than in the well-watered control. Sorghum nodal roots were unchanged. When only primary roots received water, nodal roots of both species emerged and elongated into extremely dry soil (0·6–1·5 % SWC), possibly with phloem-delivered water from the primary roots in the moist inner pot. Nodal roots were thick, short, branchless and vertical, indicating a tropism that was more pronounced in millet. Total nodal root length increased in both species when the dry soil was covered with plastic, suggesting that stubble retention or leaf mulching could facilitate nodal roots reaching deeper moist layers in dry climates. Greater nodal root length in millet than in sorghum was associated with increased shoot biomass, water uptake and water use efficiency (shoot mass per water). Millet had a more plastic response than sorghum to moisture around the nodal roots due to (1) faster growth and progression through ontogeny for earlier nodal root branch length and (2

  7. Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system.

    PubMed

    Müller, Patrick; Rogers, Katherine W; Jordan, Ben M; Lee, Joon S; Robson, Drew; Ramanathan, Sharad; Schier, Alexander F

    2012-05-11

    Biological systems involving short-range activators and long-range inhibitors can generate complex patterns. Reaction-diffusion models postulate that differences in signaling range are caused by differential diffusivity of inhibitor and activator. Other models suggest that differential clearance underlies different signaling ranges. To test these models, we measured the biophysical properties of the Nodal/Lefty activator/inhibitor system during zebrafish embryogenesis. Analysis of Nodal and Lefty gradients revealed that Nodals have a shorter range than Lefty proteins. Pulse-labeling analysis indicated that Nodals and Leftys have similar clearance kinetics, whereas fluorescence recovery assays revealed that Leftys have a higher effective diffusion coefficient than Nodals. These results indicate that differential diffusivity is the major determinant of the differences in Nodal/Lefty range and provide biophysical support for reaction-diffusion models of activator/inhibitor-mediated patterning.

  8. Differential diffusivity of Nodal and Lefty underlies a reaction-diffusion patterning system

    PubMed Central

    Müller, Patrick; Rogers, Katherine W.; Jordan, Ben M.; Lee, Joon S.; Robson, Drew; Ramanathan, Sharad; Schier, Alexander F.

    2012-01-01

    Biological systems involving short-range activators and long-range inhibitors can generate complex patterns. Reaction-diffusion models postulate that differences in signaling range are caused by differential diffusivity of inhibitor and activator. Other models suggest that differential clearance underlies different signaling ranges. To test these models, we measured the biophysical properties of the Nodal/Lefty activator/inhibitor system during zebrafish embryogenesis. Analysis of Nodal and Lefty gradients reveals that Nodals have a shorter range than Lefty proteins. Pulse-labelinganalysis indicates that Nodals and Leftys have similar clearance kinetics, whereas fluorescence recovery assays reveal that Leftys have a higher effective diffusion coefficient than Nodals. These results indicate that differential diffusivity is the major determinant of the differences in Nodal/Lefty range and provide biophysical support for reaction-diffusion models of activator/inhibitor-mediated patterning. PMID:22499809

  9. [Crucial stages of embryogenesis of R. arvalis: Part 1. Linear measurements of embryonic structures].

    PubMed

    Severtsova, E A; Severtsov, A S

    2011-01-01

    Investigations of individual variability have allowed us to reveal the crucial (= nodal) stages in embryogenesis of the moor frog (Rana arvalis Nills.). These crucial stages are: the late gastrula stage (stages 18-20), the hatching stages (stages 32-33) and, apparently, early metamorphosis (stage 39). Moreover, we have found that each embryonic structure passes through its specific crucial stages. For example, stage 34 is crucial for the trait "tail width" but is internodal for all other embryonic traits. At this stage, larva passes from an attached to a free-swimming life style. We also found considerable differences between the different frog populations in the the level of developmental variability. These differences were associated with internodal developmental stages.

  10. Approximate Schur complement preconditioning of the lowest order nodal discretizations

    SciTech Connect

    Moulton, J.D.; Ascher, U.M.; Morel, J.E.

    1996-12-31

    Particular classes of nodal methods and mixed hybrid finite element methods lead to equivalent, robust and accurate discretizations of 2nd order elliptic PDEs. However, widespread popularity of these discretizations has been hindered by the awkward linear systems which result. The present work exploits this awkwardness, which provides a natural partitioning of the linear system, by defining two optimal preconditioners based on approximate Schur complements. Central to the optimal performance of these preconditioners is their sparsity structure which is compatible with Dendy`s black box multigrid code.

  11. Topological insulating phases from two-dimensional nodal loop semimetals

    NASA Astrophysics Data System (ADS)

    Li, Linhu; Araújo, Miguel A. N.

    2016-10-01

    Starting from a minimal model for a two-dimensional nodal loop semimetal, we study the effect of chiral mass gap terms. The resulting Dirac loop anomalous Hall insulator's Chern number is the phase-winding number of the mass gap terms on the loop. We provide simple lattice models, analyze the topological phases, and generalize a previous index characterizing topological transitions. The responses of the Dirac loop anomalous Hall and quantum spin Hall insulators to a magnetic field's vector potential are also studied both in weak- and strong-field regimes, as well as the edge states in a ribbon geometry.

  12. Evaluation of the use of nodal methods for MTR neutronic analysis

    SciTech Connect

    Reitsma, F.; Mueller, E.Z.

    1997-08-01

    Although modern nodal methods are used extensively in the nuclear power industry, their use for research reactor analysis has been very limited. The suitability of nodal methods for material testing reactor analysis is investigated with the emphasis on the modelling of the core region (fuel assemblies). The nodal approach`s performance is compared with that of the traditional finite-difference fine mesh approach. The advantages of using nodal methods coupled with integrated cross section generation systems are highlighted, especially with respect to data preparation, simplicity of use and the possibility of performing a great variety of reactor calculations subject to strict time limitations such as are required for the RERTR program.

  13. Nodal line optimization and its application to violin top plate design

    NASA Astrophysics Data System (ADS)

    Yu, Yonggyun; Jang, In Gwun; Kim, In Kyum; Kwak, Byung Man

    2010-10-01

    In the literature, most problems of structural vibration have been formulated to adjust a specific natural frequency: for example, to maximize the first natural frequency. In musical instruments like a violin; however, mode shapes are equally important because they are related to sound quality in the way that natural frequencies are related to the octave. The shapes of nodal lines, which represent the natural mode shapes, are generally known to have a unique feature for good violins. Among the few studies on mode shape optimization, one typical study addresses the optimization of nodal point location for reducing vibration in a one-dimensional beam structure. However, nodal line optimization, which is required in violin plate design, has not yet been considered. In this paper, the central idea of controlling the shape of the nodal lines is proposed and then applied to violin top plate design. Finite element model for a violin top plate was constructed using shell elements. Then, optimization was performed to minimize the square sum of the displacement of selected nodes located along the target nodal lines by varying the thicknesses of the top plate. We conducted nodal line optimization for the second and the fifth modes together at the same time, and the results showed that the nodal lines obtained match well with the target nodal lines. The information on plate thickness distribution from nodal line optimization would be valuable for tailored trimming of a violin top plate for the given performances.

  14. Post-embryonic transcriptomes of the prawn Macrobrachium rosenbergii: multigenic succession through metamorphosis.

    PubMed

    Ventura, Tomer; Manor, Rivka; Aflalo, Eliahu D; Chalifa-Caspi, Vered; Weil, Simy; Sharabi, Omri; Sagi, Amir

    2013-01-01

    Like many metazoans, the freshwater prawn Macrobrachium rosenbergii begins its post-embryonic life with a set of morphologically distinct planktonic larval stages, followed by a benthic post-larval stage during which the maturing organism differs from the larvae both ecologically and physiologically. Understanding of the molecular basis underlying morphogenesis in crustaceans is limited to the observation that methyl farnesoate, the non-epoxidated form of the insect juvenile hormone, acts as the active crustacean juvenoid. Molt steroids were also linked to morphogenesis and several other molecular pathways, such as Hedgehog and Wnt, are known to underlie morphogenesis in all metazoans examined and, as such, are thought to do the same in crustaceans. Using next generation sequencing, we deep-sequenced the transcriptomes of several larval and post-larval stages. De novo assembly, followed by bioinformatics analysis, revealed that many novel transcripts are over-expressed in either larvae- or post-larvae-stage prawn, shedding light on the molecular basis underlying M. rosenbergii metamorphosis. Fast larval molting rates and periodic morphological changes were reflected in over-expression of transcripts annotated to the cell cycle, DNA replication and morphogenic pathways (i.e., Hedgehog and Wnt). Further characterization of transcripts assigned to morphogenic pathways by real-time RT-PCR reconfirmed their over-expression in larvae, albeit with a more complex expression pattern when examined in the individual developmental stages. The expression level of an orthologue of cytochrome P450, 15A1, known to epoxidize methyl farnesoate in insects, was increased in the late larval and early post-larval stages, in accordance with the role of methyl farnesoate in crustacean metamorphosis. This study exemplifies the applicability of a high-throughput sequencing approach for studying complex traits, including metamorphosis, providing new insight into this unexplored area of

  15. Post-Embryonic Transcriptomes of the Prawn Macrobrachium rosenbergii: Multigenic Succession through Metamorphosis

    PubMed Central

    Ventura, Tomer; Manor, Rivka; Aflalo, Eliahu D.; Chalifa-Caspi, Vered; Weil, Simy; Sharabi, Omri; Sagi, Amir

    2013-01-01

    Like many metazoans, the freshwater prawn Macrobrachium rosenbergii begins its post-embryonic life with a set of morphologically distinct planktonic larval stages, followed by a benthic post-larval stage during which the maturing organism differs from the larvae both ecologically and physiologically. Understanding of the molecular basis underlying morphogenesis in crustaceans is limited to the observation that methyl farnesoate, the non-epoxidated form of the insect juvenile hormone, acts as the active crustacean juvenoid. Molt steroids were also linked to morphogenesis and several other molecular pathways, such as Hedgehog and Wnt, are known to underlie morphogenesis in all metazoans examined and, as such, are thought to do the same in crustaceans. Using next generation sequencing, we deep-sequenced the transcriptomes of several larval and post-larval stages. De novo assembly, followed by bioinformatics analysis, revealed that many novel transcripts are over-expressed in either larvae- or post-larvae-stage prawn, shedding light on the molecular basis underlying M. rosenbergii metamorphosis. Fast larval molting rates and periodic morphological changes were reflected in over-expression of transcripts annotated to the cell cycle, DNA replication and morphogenic pathways (i.e., Hedgehog and Wnt). Further characterization of transcripts assigned to morphogenic pathways by real-time RT-PCR reconfirmed their over-expression in larvae, albeit with a more complex expression pattern when examined in the individual developmental stages. The expression level of an orthologue of cytochrome P450, 15A1, known to epoxidize methyl farnesoate in insects, was increased in the late larval and early post-larval stages, in accordance with the role of methyl farnesoate in crustacean metamorphosis. This study exemplifies the applicability of a high-throughput sequencing approach for studying complex traits, including metamorphosis, providing new insight into this unexplored area of

  16. Descents and nodal load in scale-free networks

    NASA Astrophysics Data System (ADS)

    Bareinboim, Elias; Barbosa, Valmir C.

    2008-04-01

    The load of a node in a network is the total traffic going through it when every node pair sustains a uniform bidirectional traffic between them on shortest paths. We express nodal load in terms of the more elementary notion of a node’s descents in breadth-first-search [(BFS) or shortest-path] trees and study both the descent and nodal-load distributions in the case of scale-free networks. Our treatment is both semianalytical (combining a generating-function formalism with simulation-derived BFS branching probabilities) and computational for the descent distribution; it is exclusively computational in the case of the load distribution. Our main result is that the load distribution, even though it can be disguised as a power law through subtle (but inappropriate) binning of the raw data, is in fact a succession of sharply delineated probability peaks, each of which can be clearly interpreted as a function of the underlying BFS descents. This find is in stark contrast with previously held belief, based on which a power law of exponent -2.2 was conjectured to be valid regardless of the exponent of the power-law distribution of node degrees.

  17. Regional non-nodal metastases of cutaneous melanoma.

    PubMed

    Cascinelli, N; Bufalino, R; Marolda, R; Belli, F; Nava, M; Galluzzo, D; Santinami, M; Levene, A

    1986-06-01

    The authors studied the prognosis of patients with so called local recurrences, satellites and in-transit metastases from cutaneous melanoma on the basis of 291 patients. These are the 19.3% of the 1503 patients with stage I and II melanoma originally submitted to surgical treatment at the National Cancer Institute of Milano (Italy). The majority of patients were males (M/F = 0.7): 102 had local recurrence, 99 in-transit metastases, 24 satellites and 66 both local and in-transit metastases. Regional non-nodal metastases were not related with the site of origin, and inadequate treatment of primary. These metastases were more frequently observed in patients who were submitted to regional node dissection no matter whether in discontinuity or in continuity with primary tumor. The frequency of regional non-nodal metastases was found to increase with increasing thickness of primary melanoma or, in stage II patients, with the number of involved nodes. Local and in-transit metastases were related with prognostic criteria in the same way. The overall survival was very close between in-transit and local metastases. Similar survival rates were observed comparing regional non-nodes and disseminated cutaneous and subcutaneous metastases. The authors conclude that the distinction between local recurrences, satellites and in-transit metastases is artificial and that these metastatic events are not prognostically dissimilar from metastases in distant skin areas.

  18. Nodal Diffusion Burnable Poison Treatment for Prismatic Reactor Cores

    SciTech Connect

    A. M. Ougouag; R. M. Ferrer

    2010-10-01

    The prismatic block version of the High Temperature Reactor (HTR) considered as a candidate Very High Temperature Reactor (VHTR)design may use burnable poison pins in locations at some corners of the fuel blocks (i.e., assembly equivalent structures). The presence of any highly absorbing materials, such as these burnable poisons, within fuel blocks for hexagonal geometry, graphite-moderated High Temperature Reactors (HTRs) causes a local inter-block flux depression that most nodal diffusion-based method have failed to properly model or otherwise represent. The location of these burnable poisons near vertices results in an asymmetry in the morphology of the assemblies (or blocks). Hence the resulting inadequacy of traditional homogenization methods, as these “spread” the actually local effect of the burnable poisons throughout the assembly. Furthermore, the actual effect of the burnable poison is primarily local with influence in its immediate vicinity, which happens to include a small region within the same assembly as well as similar regions in the adjacent assemblies. Traditional homogenization methods miss this artifact entirely. This paper presents a novel method for treating the local effect of the burnable poison explicitly in the context of a modern nodal method.

  19. Extrapolation of critical Rayleigh values using static nodal integral methods

    SciTech Connect

    Wilson, G.L.; Rydin, R.A.

    1988-01-01

    The Benard problem is the study of the convective motion of a fluid in a rectangular cavity that is uniformly heated form below. Flow bifurcation in the cavity is a function of the Rayleigh number (Ra). The time-dependent nodal integral method (TDNIM) has been reported previously; its development leads to a set of 11 equations per node. The static nodal integral method (SNIM) was derived from the TDNIM by forcing the dependent variable at adjacent time steps (one of the velocity components or temperature) to take on the node integral average value. The paper summarizes the SNIM calculation of Ra for mesh sizes ranging from 4 x 4 to 24 x 24. The numerical calculation of Ra is within plus or minus one-half unit. The relative errors are calculated based on the obtained extrapolated value of Ra{sub best}* = 2584. The paper also summarizes three-point schemes used with increasingly finer mesh combinations. This approach avoids the contamination of the results with a coarse mesh; however, the calculation on n is very sensitive to small changes in the numerical values obtained for Ra*. In this approach, the extrapolated values quickly converge to Ra*{sub e} between 2583 and 2584 with n {approx}2.0 as desired, and give a best value of Ra*{sub best} = 2584.

  20. The effects of nodality on the formation of equivalence classes.

    PubMed

    Fields, L; Adams, B J; Verhave, T; Newman, S

    1990-05-01

    A four-member equivalence class (A----B----C----D) can be formed by training AB, BC, and CD. The nodal stimuli, B and C, mediate all of the derivative (transitive and equivalence) relations in the class. The derivative relations AC, CA, BD, and DB are separated by one node, whereas AD and DA are separated by two nodes. How do the number of nodes that separate the stimuli in a derivative relation influence the induction of stimulus control exerted by that relation? Seven college students learned two four-member classes made up of nonsense syllables. After training, all derivative relations were presented repeatedly without informative feedback. Stimulus control exerted by each derivative relation was assessed concurrently. For the 7 subjects, control exerted by the derivative relations increased gradually with repeated presentations. With 6 of the 7 subjects, the one-node relations exerted more control than the two-node relations during the process. However, the disparity between the one- and two-node relations decreased with repeated presentations. Eventually, all derivative relations exerted complete control. The control exerted by derivative relations during induction was inversely related to the number of nodes separating the terms in the derivative relations. These results demonstrate that nodal distance is a determinant of the relatedness of stimuli in equivalence classes. The findings are discussed in terms of remote association, semantic memory networks, and the study of transitive inference.

  1. Tgif1 Counterbalances the Activity of Core Pluripotency Factors in Mouse Embryonic Stem Cells.

    PubMed

    Lee, Bum-Kyu; Shen, Wenwen; Lee, Jiwoon; Rhee, Catherine; Chung, Haewon; Kim, Kun-Yong; Park, In-Hyun; Kim, Jonghwan

    2015-10-01

    Core pluripotency factors, such as Oct4, Sox2, and Nanog, play important roles in maintaining embryonic stem cell (ESC) identity by autoregulatory feedforward loops. Nevertheless, the mechanism that provides precise control of the levels of the ESC core factors without indefinite amplification has remained elusive. Here, we report the direct repression of core pluripotency factors by Tgif1, a previously known terminal repressor of TGFβ/activin/nodal signaling. Overexpression of Tgif1 reduces the levels of ESC core factors, whereas its depletion leads to the induction of the pluripotency factors. We confirm the existence of physical associations between Tgif1 and Oct4, Nanog, and HDAC1/2 and further show the level of Tgif1 is not significantly altered by treatment with an activator/inhibitor of the TGFβ/activin/nodal signaling. Collectively, our findings establish Tgif1 as an integral member of the core regulatory circuitry of mouse ESCs that counterbalances the levels of the core pluripotency factors in a TGFβ/activin/nodal-independent manner. PMID:26411691

  2. Distal end of the atrioventricular nodal artery predicts the risk of atrioventricular block during slow pathway catheter ablation of atrioventricular nodal re-entrant tachycardia

    PubMed Central

    Lin, J; Huang, S; Lai, L; Lin, L; Chen, J; Tseng, Y; Lien, W

    2000-01-01

    OBJECTIVE—To search for a reliable anatomical landmark within Koch's triangle to predict the risk of atrioventricular (AV) block during radiofrequency slow pathway catheter ablation of AV nodal re-entrant tachycardia (AVNRT).
PATIENTS AND METHODS—To test the hypothesis that the distal end of the AV nodal artery represents the anatomical location of the AV node, and thus could be a useful landmark for predicting the risk of AV block, 128 consecutive patients with AVNRT receiving slow pathway catheter ablation were prospectively studied in two phases. In phase I (77 patients), angiographic demonstration of the AV nodal artery and its ending was performed at the end of the ablation procedure, whereas in the subsequent phase II study (51 patients), the angiography was performed immediately before catheter ablation to assess the value of identifying this new landmark in reducing the risk of AV block. Multiple electrophysiologic and anatomical parameters were analysed. The former included the atrial activation sequence between the His bundle recording site (HBE) and the coronary sinus orifice or the catheter ablation site, either during AVNRT or during sinus rhythm. The latter included the spatial distances between the distal end of the AV nodal artery and the HBE and the final catheter ablation site, and the distance between the HBE and the tricuspid border at the coronary sinus orifice floor.
RESULTS—In phase I, nine of the 77 patients had complications of transient (seven patients) or permanent (two patients) complete AV block during stepwise, anatomy guided slow pathway catheter ablation. These nine patients had a wider distance between the HBE and the distal end of the AV nodal artery, and a closer approximation of the catheter ablation site to the distal end of the AV nodal artery, which independently predicted the risk of AV block. In contrast, none of the available electrophysiologic parameters were shown to be reliable. When the distance between

  3. The embryonic stem cell test.

    PubMed

    Schulpen, Sjors H W; Piersma, Aldert H

    2013-01-01

    The embryonic stem cell test is an animal-free alternative test method for developmental toxicity. Mouse embryonic stem cells are cultured in a hanging drop method to form embryoid bodies. These embryoid bodies, when plated on tissue culture dishes, differentiate to form contracting myocardial cell foci within 10 days. Inhibition of cardiomyocyte differentiation by test compounds serves as the end point of the assay, as monitored by counting contracting muscle foci under the microscope.

  4. Modulation of ornithine decarboxylase activity in the normal and regenerating rat liver by various doses of the peptide morphogen of Hydra

    SciTech Connect

    Yarygin, K.N.; Kazimirskii, A.N.; Kositskii, G.I.; Rubina, A.Yu.; Vinogradov, V.A.; Pylaev, A.S.

    1986-11-01

    In this investigation, changes in ornithine decarboxylase (ODC) activity were studied in the normal and regenerating liver of rats receiving injections of various doses of Hydra peptide morphogen (HPM). Activity of ODC was determined by a radioisotope method based on liberation of /sup 14/CO/sub 2/ from L-(1-/sup 14/C)-ornithine. The results indicate in the author's opinion that HPM may have a role in the regulation of anabolic processes and, in particular, of regenerative processes in mammals.

  5. The morphogen Decapentaplegic employs a two-tier mechanism to activate target retinal determining genes during ectopic eye formation in Drosophila

    PubMed Central

    Aggarwal, Poonam; Gera, Jayati; Mandal, Lolitika; Mandal, Sudip

    2016-01-01

    Understanding the role of morphogen in activating its target genes, otherwise epigenetically repressed, during change in cell fate specification is a very fascinating yet relatively unexplored domain. Our in vivo loss-of-function genetic analyses reveal that specifically during ectopic eye formation, the morphogen Decapentaplegic (Dpp), in conjunction with the canonical signaling responsible for transcriptional activation of retinal determining (RD) genes, triggers another signaling cascade. Involving dTak1 and JNK, this pathway down-regulates the expression of polycomb group of genes to do away with their repressive role on RD genes. Upon genetic inactivation of members of this newly identified pathway, the canonical Dpp signaling fails to trigger RD gene expression beyond a threshold, critical for ectopic photoreceptor differentiation. Moreover, the drop in ectopic RD gene expression and subsequent reduction in ectopic photoreceptor differentiation resulting from inactivation of dTak1 can be rescued by down-regulating the expression of polycomb group of genes. Our results unravel an otherwise unknown role of morphogen in coordinating simultaneous transcriptional activation and de-repression of target genes implicating its importance in cellular plasticity. PMID:27270790

  6. Beam Elements with Trapezoidal Cross Section Deformation Modes Based on the Absolute Nodal Coordinate Formulation

    NASA Astrophysics Data System (ADS)

    Matikainen, Marko K.; Dmitrochenko, Oleg; Mikkola, Aki

    2010-09-01

    In this study, higher order beam elements are developed based on the absolute nodal coordinate formulation. The absolute nodal coordinate formulation is a finite element procedure that was recently proposed for flexible multibody applications. Many different elements based on the absolute nodal coordinate formulation are introduced, but still the beam elements are not able to describe the trapezoidal cross section mode. This leads to the locking phenomena, and therefore, the beam elements based on the absolute nodal coordinate formulation with three dimensional elasticity converge to an inexact solution. In order to avoid the locking phenomena, the trapezoidal cross section deformation mode is included in the beam elements based on the absolute nodal coordinate with additional degrees of freedom. The proper description for the trapezoidal cross section deformation is important for the continuum beam elements based on three-dimensional elasticity where the material model is often based on general continuum mechanics.

  7. The Immunologic Properties of Bone Morphogenic Protein Receptor IB Positive Subpopulation before and after Osteogenic Differentiation in Mouse Dermis

    PubMed Central

    Wang, Tao; Xu, Hua; Zhang, Yi; Dong, Jia-Sheng

    2016-01-01

    We have previously reported that human dermal bone morphogenic protein receptor (BMPR) IB positive subpopulation had a high osteogenic differentiation potential and may be a promising cell source for allogeneic bone tissue engineering. In this study, the immunologic properties of dermal BMPR-IB+ subpopulation before and after osteogenic differentiation were reported. The results confirmed that dermal BMPR-IB+ cells possessed a similar osteogenic differentiation potential with bone marrow mesenchymal stromal cells in a mouse model. Furthermore, the expression of immune rejection-related surface antigens such as major histocompatibility class II and co-stimulatory proteins (CD40, CD80, and CD86) were absent on dermal BMPRIB+ cells. Dermal BMPRIB+ cells elicited no proliferation of allogeneic splenocytes and suppressed the proliferation of stimulated immune cells. Interestingly, osteogenic differentiation in vitro had no adverse effect on the immunological features of these cells. Most importantly, inducible NO synthase (iNOS) was involved in immunoregulatory effects by undifferentiated BMPRIB+ fibroblasts, whereas indoleamine 2,3-dioxygenase (IDO) activity was related to mediating immunomodulatory function by osteogenic differentiated BMPRIB+ fibroblasts. In conclusion, dermal BMPRIB+ cells have a low immunogenicity and possess immunosuppressive capacity before and after osteogenic differentiation in vitro, which would facilitate the allotransplantation in the future. However, mechanisms mediating immunoregulatory property between undifferentiated and osteogenic differentiated BMPRIB+ fibroblasts may be different and need further investigation. PMID:27552226

  8. Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells.

    PubMed

    Kim, Jungju; Kim, In Sook; Cho, Tae Hyung; Lee, Kyu Back; Hwang, Soon Jung; Tae, Giyoong; Noh, Insup; Lee, Sang Hoon; Park, Yongdoo; Sun, Kyung

    2007-04-01

    Acrylated hyaluronic acid (HA) was used as a scaffold for bone morphogenic protein-2 (BMP-2) and human mesenchymal stem cells (hMSCs) for rat calvarial defect regeneration. HA was acrylated by two-step reactions: (1) introduction of an amine group using adipic acid dihydrazide (ADH); (2) acrylation by N-acryloxysuccinimide. Tetrathiolated poly(ethylene) glycol (PEG-SH(4)) was used as a cross-linker by a Michael-type addition reaction and the hydrogel was formed within 10min under physiological conditions. This hydrogel is degraded completely by 100U/ml hyaluronidase in vitro. hMSCs and/or BMP-2 was added during gelation. Cellular viability in vitro was increased up to 55% in the hydrogels with BMP-2 compared with the control. For in vivo calvarial defect regeneration, five different samples (i.e., control, hydrogel, hydrogel with BMP-2, hydrogel with MSCs, and hydrogel with BMP-2 and MSCs) were implanted for 4 weeks. The histological results demonstrated that the hydrogels with BMP-2 and MSCs had the highest expression of osteocalcin and mature bone formation with vascular markers, such as CD31 and vascular endothelial growth factors, compared with the other samples. This study demonstrated that HA base hydrogel can be used for cell and growth factor carriers for tissue regeneration. PMID:17208295

  9. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

    PubMed

    Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

    2015-03-01

    The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines.

  10. The Immunologic Properties of Bone Morphogenic Protein Receptor IB Positive Subpopulation before and after Osteogenic Differentiation in Mouse Dermis.

    PubMed

    He, Jin-Guang; Wang, Ting-Liang; Wang, Tao; Xu, Hua; Zhang, Yi; Dong, Jia-Sheng

    2016-01-01

    We have previously reported that human dermal bone morphogenic protein receptor (BMPR) IB positive subpopulation had a high osteogenic differentiation potential and may be a promising cell source for allogeneic bone tissue engineering. In this study, the immunologic properties of dermal BMPR-IB+ subpopulation before and after osteogenic differentiation were reported. The results confirmed that dermal BMPR-IB+ cells possessed a similar osteogenic differentiation potential with bone marrow mesenchymal stromal cells in a mouse model. Furthermore, the expression of immune rejection-related surface antigens such as major histocompatibility class II and co-stimulatory proteins (CD40, CD80, and CD86) were absent on dermal BMPRIB+ cells. Dermal BMPRIB+ cells elicited no proliferation of allogeneic splenocytes and suppressed the proliferation of stimulated immune cells. Interestingly, osteogenic differentiation in vitro had no adverse effect on the immunological features of these cells. Most importantly, inducible NO synthase (iNOS) was involved in immunoregulatory effects by undifferentiated BMPRIB+ fibroblasts, whereas indoleamine 2,3-dioxygenase (IDO) activity was related to mediating immunomodulatory function by osteogenic differentiated BMPRIB+ fibroblasts. In conclusion, dermal BMPRIB+ cells have a low immunogenicity and possess immunosuppressive capacity before and after osteogenic differentiation in vitro, which would facilitate the allotransplantation in the future. However, mechanisms mediating immunoregulatory property between undifferentiated and osteogenic differentiated BMPRIB+ fibroblasts may be different and need further investigation. PMID:27552226

  11. Magnetic response in three-dimensional nodal semimetals

    NASA Astrophysics Data System (ADS)

    Koshino, Mikito; Hizbullah, Intan Fatimah

    We study the magnetic response in various three-dimensional gapless systems, including Dirac and Weyl semimetals and a line-node semimetal. We show that the susceptibility is decomposed into the orbital term, the spin term and also the spin-orbit cross term which is caused by the spin-orbit interaction. We show that the orbital susceptibility logarithmically diverges at the band touching energy in the point-node case, while it exhibits a stronger delta-function singularity in the line node case. The spin-orbit cross term is shown to be paramagnetic in the electron side while diamagnetic in the hole side, in contrast with other two terms which are both even functions in Fermi energy. The spin-orbit cross term in the nodal semimetal is found to be directly related to the chiral surface current induced by the topological surface modes.

  12. Magnetic susceptibility in three-dimensional nodal semimetals

    NASA Astrophysics Data System (ADS)

    Koshino, Mikito; Hizbullah, Intan Fatimah

    2016-01-01

    We study the magnetic susceptibility in various three-dimensional gapless systems, including Dirac and Weyl semimetals, and a line-node semimetal. The susceptibility is decomposed into the orbital term, the spin term and also the spin-orbit cross term, which is caused by the spin-orbit interaction. We show that the orbital susceptibility logarithmically diverges at the band touching energy in the point-node case, while it exhibits a stronger δ -function singularity in the line node case. The spin-orbit cross term is shown to be paramagnetic in the electron side while diamagnetic in the hole side, in contrast with other two terms which are both even functions in Fermi energy. The spin-orbit cross term in the nodal semimetal is found to be directly related to the chiral surface current induced by the topological surface modes.

  13. Typical nodal calcifications in the maxillofacial region: a case report

    PubMed Central

    Wu, Guomin; Sun, Xiumei; Ni, Shilei; Zhang, Zhimin

    2014-01-01

    Multiple nodal calcifications in the maxillofacial region are very rare. This case report described a 49-year-old female patient diagnosed with calcified lymph nodes due to chronic inflammation of the lymphatic nodes, including the parotid lymphatic nodes, the posterior auricular lymphatic nodes and submandibular lymphatic nodes in the right maxillofacial region. In clinical practice, we conducted ultrasonography, three-dimensional reconstruction of CT and sialography make a preliminary diagnosis. Then we took surgery, while removing the calcified blocks within the lymphatic node and cleaning the wound cavity. After surgery, we used anti-inflammatory therapy for one week. Six months follow-up indicated no evidence of other calcified lymph nodes infection. PMID:25356188

  14. Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma.

    PubMed

    Na'ara, Shorook; Amit, Moran; Fridman, Eran; Gil, Ziv

    2016-01-28

    Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC.

  15. Coexistence of Weyl fermion and massless triply degenerate nodal points

    NASA Astrophysics Data System (ADS)

    Weng, Hongming; Fang, Chen; Fang, Zhong; Dai, Xi

    2016-10-01

    By using first-principles calculations, we propose that WC-type ZrTe is a new type of topological semimetal (TSM). It has six pairs of chiral Weyl nodes in its first Brillouin zone, but it is distinguished from other existing TSMs by having an additional two paris of massless fermions with triply degenerate nodal points as proposed in the isostructural compounds TaN and NbN. The mirror symmetry, threefold rotational symmetry, and time-reversal symmetry require all of the Weyl nodes to have the same velocity vectors and locate at the same energy level. The Fermi arcs on different surfaces are shown, which may be measured by future experiments. It demonstrates that the "material universe" can support more intriguing particles simultaneously.

  16. Mapping of nodal disease in locally advanced prostate cancer: Rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy

    SciTech Connect

    Shih, Helen A. . E-mail: hshih@partners.org; Harisinghani, Mukesh; Zietman, Anthony L.; Wolfgang, John A.; Saksena, Mansi; Weissleder, Ralph

    2005-11-15

    Purpose: Toxicity from pelvic irradiation could be reduced if fields were limited to likely areas of nodal involvement rather than using the standard 'four-field box.' We employed a novel magnetic resonance lymphangiographic technique to highlight the likely sites of occult nodal metastasis from prostate cancer. Methods and Materials: Eighteen prostate cancer patients with pathologically confirmed node-positive disease had a total of 69 pathologic nodes identifiable by lymphotropic nanoparticle-enhanced MRI and semiquantitative nodal analysis. Fourteen of these nodes were in the para-aortic region, and 55 were in the pelvis. The position of each of these malignant nodes was mapped to a common template based on its relation to skeletal or vascular anatomy. Results: Relative to skeletal anatomy, nodes covered a diffuse volume from the mid lumbar spine to the superior pubic ramus and along the sacrum and pelvic side walls. In contrast, the nodal metastases mapped much more tightly relative to the large pelvic vessels. A proposed pelvic clinical target volume to encompass the region at greatest risk of containing occult nodal metastases would include a 2.0-cm radial expansion volume around the distal common iliac and proximal external and internal iliac vessels that would encompass 94.5% of the pelvic nodes at risk as defined by our node-positive prostate cancer patient cohort. Conclusions: Nodal metastases from prostate cancer are largely localized along the major pelvic vasculature. Defining nodal radiation treatment portals based on vascular rather than bony anatomy may allow for a significant decrease in normal pelvic tissue irradiation and its associated toxicities.

  17. Application of the Absolute Nodal Co-Ordinate Formulation to Multibody System Dynamics

    NASA Astrophysics Data System (ADS)

    Escalona, J. L.; Hussien, H. A.; Shabana, A. A.

    1998-07-01

    The floating frame of reference formulation is currently the most widely used approach in flexible multibody simulations. The use of this approach, however, has been limited to small deformation problems. In this investigation, the computer implementation of the newabsolute nodal co-ordinate formulationand its use in the small and large deformation analysis of flexible multibody systems that consist of interconnected bodies are discussed. While in the floating frame of reference formulation a mixed set of absolute reference and local elastic co-ordinates are used, in the absolute nodal co-ordinate formulation only absolute co-ordinates are used. In the absolute nodal co-ordinate formulation, new interpretation of the nodal co-ordinates of the finite elements is used. No infinitesimal or finite rotations are used as nodal co-ordinates from beams and plates, instead, global slopes are used to define the element nodal co-ordinates. Using this interpretation of the element co-ordinates, beams and plates can be considered as isoparametric elements, and as a result, exact modelling of the rigid body dynamics can be obtained using the element shape function and the absolute nodal co-ordinates. Unlike the floating frame of reference approach, no co-ordinate transformation is required in order to determine the element inertia. The mass matrix of the finite elements is a constant matrix, and therefore, the centrifugal and Coriolis forces are equal to zero when the absolute nodal co-ordinate formulation is used. Another advantage of using the absolute nodal co-ordinate formulation in the dynamic simulation of multibody systems is its simplicity in imposing some of the joint constraints and also its simplicity in formulating the generalized forces due to spring-damper elements. The results obtained in this investigation show an excellent agreement with the results obtained using the floating frame of reference formulation when large rotation-small deformation problems are

  18. Nodal signaling is required for closure of the anterior neural tube in zebrafish

    PubMed Central

    Aquilina-Beck, Allisan; Ilagan, Kristine; Liu, Qin; Liang, Jennifer O

    2007-01-01

    Background Nodals are secreted signaling proteins with many roles in vertebrate development. Here, we identify a new role for Nodal signaling in regulating closure of the rostral neural tube of zebrafish. Results We find that the neural tube in the presumptive forebrain fails to close in zebrafish Nodal signaling mutants. For instance, the cells that will give rise to the pineal organ fail to move from the lateral edges of the neural plate to the midline of the diencephalon. The open neural tube in Nodal signaling mutants may be due in part to reduced function of N-cadherin, a cell adhesion molecule expressed in the neural tube and required for neural tube closure. N-cadherin expression and localization to the membrane are reduced in fish that lack Nodal signaling. Further, N-cadherin mutants and morphants have a pineal phenotype similar to that of mutants with deficiencies in the Nodal pathway. Overexpression of an activated form of the TGFβ Type I receptor Taram-A (Taram-A*) cell autonomously rescues mesendoderm formation in fish with a severe decrease in Nodal signaling. We find that overexpression of Taram-A* also corrects their open neural tube defect. This suggests that, as in mammals, the mesoderm and endoderm have an important role in regulating closure of the anterior neural tube of zebrafish. Conclusion This work helps establish a role for Nodal signals in neurulation, and suggests that defects in Nodal signaling could underlie human neural tube defects such as exencephaly, a fatal condition characterized by an open neural tube in the anterior brain. PMID:17996054

  19. The accuracy of preoperative axillary nodal staging in primary breast cancer by ultrasound is modified by nodal metastatic load and tumor biology

    PubMed Central

    Dihge, Looket; Grabau, Dorthe A.; Rasmussen, Rogvi W.; Bendahl, Pär-Ola; Rydén, Lisa

    2016-01-01

    Abstract Background The outcome of axillary ultrasound (AUS) with fine-needle aspiration biopsy (FNAB) in the diagnostic work-up of primary breast cancer has an impact on therapy decisions. We hypothesize that the accuracy of AUS is modified by nodal metastatic burden and clinico-pathological characteristics. Material and methods The performance of AUS and AUS-guided FNAB for predicting nodal metastases was assessed in a prospective breast cancer cohort subjected for surgery during 2009–2012. Predictors of accuracy were included in multivariate analysis. Results AUS had a sensitivity of 23% and a specificity of 95%, while AUS-guided FNAB obtained 73% and 100%, respectively. AUS-FNAB exclusively detected macro-metastases (median four metastases) and identified patients with more extensive nodal metastatic burden in comparison with sentinel node biopsy. The accuracy of AUS was affected by metastatic size (OR 1.11), obesity (OR 2.46), histological grade (OR 4.43), and HER2-status (OR 3.66); metastatic size and histological grade were significant in the multivariate analysis. Conclusions The clinical utility of AUS in low-risk breast cancer deserves further evaluation as the accuracy decreased with a low nodal metastatic burden. The diagnostic performance is modified by tumor and clinical characteristics. Patients with nodal disease detected by AUS-FNAB represent a group for whom neoadjuvant therapy should be considered. PMID:27050668

  20. Segmentation and millennium recurrence interval of morphogenic earthquakes of the Longmen Shan Thrust Belt, central China (Invited)

    NASA Astrophysics Data System (ADS)

    Lin, A.

    2013-12-01

    . Field investigation, paleoseismic and archaeological evidence, and radiocarbon dating results reveal that at least four large morphogenic earthquakes including the 2008 Mw7.9 Wenchuan earthquakes occurred in the Sichuan region during the late Tang-Song (AD 800-1000), Han (206 BC to AD 220), and late Shang-Chunqiu (1200-800 BC) dynasties, comparable with the 2008 Wenchuan earthquake in its seismic intensity, suggesting an average millennium recurrence interval for Wenchuan-magnitude (M = ˜8) earthquakes in the late Holocene within the LSTB. This finding is in contrast with previous estimates of 2,000-10,000 years for the recurrence interval of morphogenic earthquakes within the LSTB, as obtained from long-term slip rates based on the Global Positioning System and geological data, thereby necessitating substantial modifications to existing seismic-hazard models for the densely populated region at the eastern marginal zone of the Tibetan Plateau. Our results confirm that the present-day shortening strain upon the eastern margin of the Tibetan Plateau is mostly released by seismic thrusting and folding with strike-slip partitioning along the active faults within the LSTB. References Lin et al., 2009, Tectonophysics, 471, 203-215; 2) Lin et al., 2010, J. Seismol., 14, 615-628; 3) Lin et al., 2010, Tectonophysics, 491, 21-34; 4) Lin, A., 2011, Geology, 39, 547-550; 5) Lin et al., 2012. Tectonophysics, 522-523, 243-252; 6) Lin et al., 2013, Tectonophysics, submitted.

  1. The stationary-phase morphogene bolA from Escherichia coli is induced by stress during early stages of growth.

    PubMed

    Santos, J M; Freire, P; Vicente, M; Arraiano, C M

    1999-05-01

    The Escherichia coli morphogene bolA causes round morphology when overexpressed. The expression of bolA is mainly regulated by a sigmas-dependent gearbox promoter bolA1p. Such regulation results in increased relative levels of expression at slow growth rates, as seen with those attained at the onset of stationary phase. We demonstrate that bolA1p is also induced during early logarithmic growth in response to several forms of stress, and that this induction can be partially sigmas independent. Sudden carbon starvation results in a 17-fold increase in mRNA levels derived from bolA1p 1 h after stress imposition. Increased osmolarity results in a more than 20-fold increase after the same period. Considerable increases in bolA1p mRNA levels were also detected as a result of heat shock, acidic stress and oxidative stress, which has been shown to inhibit sigmas translation. The orders of magnitude of bolA1p induction in log phase due to sudden starvation, osmotic shock and oxidative stress surpass the levels reached in stationary phase. Under sudden carbon starvation and osmotic shock, the cells changed their morphology, resembling those cells in which bolA is overexpressed in stationary phase. Increased expression and morphological changes due to sudden carbon starvation and osmotic shock still occur when sigmaS is not present in a rpoS- background. The results show that expression of bolA is not confined to stationary phase, but it can also play an important role in general stress response. We propose that bolA1p stress induction overrides the normal regulation imposed by growth rate, which is strictly the result of sigmaS-directed transcription.

  2. In vivo effect of immobilisation of bone morphogenic protein 2 on titanium implants through nano-anchored oligonucleotides.

    PubMed

    Schliephake, H; Rublack, J; Aeckerle, N; Förster, A; Schwenzer, B; Reichert, J; Scharnweber, D

    2015-07-27

    The aim of the present study was to test the hypothesis that immobilisation of bone morphogenic proteins on the surface of titanium implants through nano-anchored oligonucleotides can enhance peri-implant bone formation. Non-coding 60-mer DNA oligonucleotides (ODN) were anchored to the surface of custom made sandblasted acid etched (SAE) titanium screw implants through anodic polarisation, gamma-sterilised with a standard dose of 25 kGy, and were hybridised with complementary 30-mer strands of DNA oligonucleotides conjugated to rhBMP2. Blank SAE implants, SAE implants with nano-anchored ODN and SAE implants with nano-anchored ODN and non-conjugated rhBMP2 served as controls. The implants were inserted into the tibiae of 36 Sprague Dawley rats. Perforations at the head and the tip of the implants allowed for bone ingrowth. Bone ingrowth into perforations and bone implant contact (BIC) as well as bone density (BD) at a distance of 200 µm from the implant surface were assessed after 1 , 4 and 13 weeks. Implants with nano-anchored ODN strands hybridised with conjugated rhBMP2 exhibited enhanced bone ingrowth into the perforations and increased BIC after 1 week as well as increased BIC after 4 weeks compared to controls. No difference was seen after 13 weeks. Bone density around the outer implant surface did not differ significantly at any of the intervals. It is concluded that rhBMP2 immobilised on the surface of titanium implants through nano-anchored oligonucleotide strands can enhance bone implant contact. The conditions of sterilisation tested allowed for handling under clinically relevant conditions.

  3. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    PubMed Central

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

    2016-01-01

    In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

  4. Micropropagation of Calophyllum brasiliense (Cambess.) from nodal segments.

    PubMed

    Silveira, S S; Cordeiro-Silva, R; Degenhardt-Goldbach, J; Quoirin, M

    2016-05-01

    Micropropagation of Calophyllum brasiliense Cambess. (Clusiaceae) is a way to overcome difficulties in achieving large-scale plant production, given the recalcitrant nature of the seeds, irregular fructification and absence of natural vegetative propagation of the species. Cultures were established using nodal segments 2 cm in length, obtained from 1-2 year old seedlings, maintained in a greenhouse. Mercury chloride and Plant Preservative Mixture™ were used in the surface sterilizing stage, better results being achieved with Plant Preservative Mixture™ incorporation in culture medium, at any concentration. Polyvinylpyrrolidone, activated charcoal, cysteine, ascorbic acid or citric acid were added to the culture medium to avoid oxidation. After 30 days of culture, polyvinylpirrolidone and ascorbic acid gave better results, eliminating oxidation in most explants. For shoot multiplication, benzylaminopurine was used in concentrations of 4.4 and 8.8 µM in Woody Plant Medium, resulting in an average of 4.43 and 4.68 shoots per explant, respectively, after 90 days. Indole-3-butyric acid and α-naphthalene acetic acid were used to induce root formation, reaching a maximum rooting rate of 24% with 20µM α-naphthalene acetic acid. For acclimatization. the rooted plants were transferred to Plantmax® substrate and cultured in a greenhouse, reaching 79% of survival after 30 days and 60% after one year.

  5. Micropropagation of commercially cultivated Henna (Lawsonia inermis) using nodal explants.

    PubMed

    Ram, Kheta; Shekhawat, N S

    2011-07-01

    Lawsonia inermis Linn. (Mehandi) is cultivated as cash crop in India particularly in Sojat area of Pali district, Rajasthan. Present investigation describes an efficient regeneration system for elite genotype of L. inermis using nodal segments. Optimum response in terms of percent cultures responding, days to bud break and average shoot length was observed on MS medium supplemented with 6-benzylaminopurine (BA; 2.0 mg l(-1)). Shoot multiplication was influenced by plant growth regulators, repeated transfer of explants and addition of ammonium sulphate. Maximum shoots were regenerated on MS medium supplemented with BA (0.25 mg l(-1)), kinetin (Kn; 0.25 mg l(-1)), indole-3-acetic acid (IAA; 0.1 mg l(-1)) and ammonium sulphate (150 mg l(-1)). To reduce resources, time and labours costs, we have also attempted ex vitro rooting of shoots. About 95 % shoots were rooted ex vitro on soilrite after treatment with indole-3-butyric acid (IBA; 300 mg l(-1)) and 2-naphthoxy acetic acid (NOA; 100 mg l(-1)) and establishment in soil successfully.

  6. Heterogeneous nodal responses in cascade dynamics on multiplex networks

    NASA Astrophysics Data System (ADS)

    Lee, Kyu-Min; Brummitt, Charles D.; Goh, Kwang-Il

    2014-03-01

    Structure and dynamics of multiplex network systems have been intensively studied recently, revealing nontrivial results such as facilitated cascading failures and new type of phase transitions unforeseen in the single-level systems. However, most studies about multi-layered, network of networks have mainly considered the case of single nodal response to multiple layers, that is, every node responds to the multiple layers in identical way. Most complex systems like human society, however, function not only through various kinds of relations but also through heterogeneous response behavior across agents, indicating a new level of complexity. To address it, here we formulate a threshold cascade model on multiplex networks with a mixture of two response functions: OR and AND rules. For the OR response, nodes are activated if enough neighbors in any layer are active, whereas for the AND response, the nodes activate only if enough neighbors in all layers are active. Coexistence of these two response rules is shown to control between facilitation and inhibition of cascading failures, and moreover, it can also control the type of transitions to global cascades between continuous and discontinuous ones. We will discuss the implication of the results in the context of social dynamics.

  7. Micropropagation of Calophyllum brasiliense (Cambess.) from nodal segments.

    PubMed

    Silveira, S S; Cordeiro-Silva, R; Degenhardt-Goldbach, J; Quoirin, M

    2016-05-01

    Micropropagation of Calophyllum brasiliense Cambess. (Clusiaceae) is a way to overcome difficulties in achieving large-scale plant production, given the recalcitrant nature of the seeds, irregular fructification and absence of natural vegetative propagation of the species. Cultures were established using nodal segments 2 cm in length, obtained from 1-2 year old seedlings, maintained in a greenhouse. Mercury chloride and Plant Preservative Mixture™ were used in the surface sterilizing stage, better results being achieved with Plant Preservative Mixture™ incorporation in culture medium, at any concentration. Polyvinylpyrrolidone, activated charcoal, cysteine, ascorbic acid or citric acid were added to the culture medium to avoid oxidation. After 30 days of culture, polyvinylpirrolidone and ascorbic acid gave better results, eliminating oxidation in most explants. For shoot multiplication, benzylaminopurine was used in concentrations of 4.4 and 8.8 µM in Woody Plant Medium, resulting in an average of 4.43 and 4.68 shoots per explant, respectively, after 90 days. Indole-3-butyric acid and α-naphthalene acetic acid were used to induce root formation, reaching a maximum rooting rate of 24% with 20µM α-naphthalene acetic acid. For acclimatization. the rooted plants were transferred to Plantmax® substrate and cultured in a greenhouse, reaching 79% of survival after 30 days and 60% after one year. PMID:27143061

  8. Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma.

    PubMed

    Hoskin, P J; Díez, P; Gallop-Evans, E; Syndikus, I; Bates, A; Bayne, M

    2016-01-01

    Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma.

  9. Relation between finite element methods and nodal methods in transport theory

    SciTech Connect

    Walters, W.F.

    1985-01-01

    This paper examines the relationship between nodal methods and finite-element methods for solving the discrete-ordinates form of the transport equation in x-y geometry. Specifically, we will examine the relation of three finite-element schemes to the linear-linear (LL) and linear-nodal (LN) nodal schemes. The three finite-element schemes are the linear-continuous-diamond-difference (DD) scheme, the linear-discontinuous (LD) scheme, and the quadratic-discontinuous (QD) scheme. A brief derivation of the (LL) and (LN) nodal schemes is given in the third section of this paper. The approximations that cause the LL scheme to reduce to the DD, LD, and QD schemes are then indicated. An extremely simple method of deriving the finite-element schemes is then introduced.

  10. Dose-dependent Nodal/Smad signals pattern the early mouse embryo.

    PubMed

    Robertson, Elizabeth J

    2014-08-01

    Nodal signals in the early post-implantation stage embryo are essential to establish initial proximal-distal (P-D) polarity and generate the final anterior-posterior (A-P) body axis. Nodal signaling in the epiblast results in the phosphorylation of Smad2 in the overlying visceral endoderm necessary to induce the AVE, in part via Smad2-dependent activation of the T-box gene Eomesodermin. Slightly later following mesoderm induction a continuum of dose-dependent Nodal signaling during the process of gastrulation underlies specification of mesodermal and definitive endoderm progenitors. Dynamic Nodal expression during the critical 72 h time window immediately following implantation, accomplished by a series of feed-back and feed-forward mechanisms serves to provide key positional cues required for establishment of the body plan and controls cell fate decisions in the early mammalian embryo. PMID:24704361

  11. Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma.

    PubMed

    Hoskin, P J; Díez, P; Gallop-Evans, E; Syndikus, I; Bates, A; Bayne, M

    2016-01-01

    Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma. PMID:26456507

  12. ANOVA-HDMR structure of the higher order nodal diffusion solution

    SciTech Connect

    Bokov, P. M.; Prinsloo, R. H.; Tomasevic, D. I.

    2013-07-01

    Nodal diffusion methods still represent a standard in global reactor calculations, but employ some ad-hoc approximations (such as the quadratic leakage approximation) which limit their accuracy in cases where reference quality solutions are sought. In this work we solve the nodal diffusion equations utilizing the so-called higher-order nodal methods to generate reference quality solutions and to decompose the obtained solutions via a technique known as High Dimensional Model Representation (HDMR). This representation and associated decomposition of the solution provides a new formulation of the transverse leakage term. The HDMR structure is investigated via the technique of Analysis of Variance (ANOVA), which indicates why the existing class of transversely-integrated nodal methods prove to be so successful. Furthermore, the analysis leads to a potential solution method for generating reference quality solutions at a much reduced calculational cost, by applying the ANOVA technique to the full higher order solution. (authors)

  13. Nodal signaling in Xenopus gastrulae is cell-autonomous and patterned by beta-catenin.

    PubMed

    Hashimoto-Partyka, Minako K; Yuge, Masahiro; Cho, Ken W Y

    2003-01-01

    The classical three-signal model of amphibian mesoderm induction and more recent modifications together propose that an activin-like signaling activity is uniformly distributed across the vegetal half of the Xenopus blastula and that this activity contributes to mesoderm induction. In support of this, we have previously shown that the activin-response element (DE) of the goosecoid promoter is uniformly activated across the vegetal half of midgastrula-stage embryos. Here, we further examine the nature of this activity by measuring DE activation by endogenous signals over time. We find that the spatiotemporal pattern of DE activation is much more dynamic than was previously appreciated and also conclude that DE(6X)Luc activity reflects endogenous nodal signaling in the embryo. Using both the DE(6X)Luc construct and endogenous Xbra and Xgsc expression as read-outs for nodal activity, and the cleavage-mutant version of Xnr2 (CmXnr2) to regionally suppress endogenous nodal activity, we demonstrate that nodal signals act cell-autonomously in Xenopus gastrulae. Nodal-expressing cells are unable to rescue either reporter gene activation or target gene expression in distant nodal-deficient cells, suggesting that nodals function at short range in this context. Finally, we show that DE activation by endogenous signals occurs in the absence of dorsal beta-catenin-mediated signaling, but that the timing of dorsal initiation is altered. We conclude that nodal signals in Xenopus gastrulae function cell autonomously at short ranges and that the spatiotemporal pattern of this signaling along the dorsoventral axis is regulated by maternal Wnt-like signaling. PMID:12490202

  14. Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis.

    PubMed

    Gato, Angel; Desmond, Mary E

    2009-03-15

    The key focus of this review is that both the neuroepithelium and embryonic cerebrospinal fluid (CSF) work in an integrated way to promote embryonic brain growth, morphogenesis and histiogenesis. The CSF generates pressure and also contains many biologically powerful trophic factors; both play key roles in early brain development. Accumulation of fluid via an osmotic gradient creates pressure that promotes rapid expansion of the early brain in a developmental regulated way, since the rates of growth differ between the vesicles and for different species. The neuroepithelium and ventricles both contribute to this growth but by different and coordinated mechanisms. The neuroepithelium grows primarily by cell proliferation and at the same time the ventricle expands via hydrostatic pressure generated by active transport of Na(+) and transport or secretion of proteins and proteoglycans that create an osmotic gradient which contribute to the accumulation of fluid inside the sealed brain cavity. Recent evidence shows that the CSF regulates relevant aspects of neuroepithelial behavior such as cell survival, replication and neurogenesis by means of growth factors and morphogens. Here we try to highlight that early brain development requires the coordinated interplay of the CSF contained in the brain cavity with the surrounding neuroepithelium. The information presented is essential in order to understand the earliest phases of brain development and also how neuronal precursor behavior is regulated. PMID:19154733

  15. Distinct cis regulatory elements govern the expression of TAG1 in embryonic sensory ganglia and spinal cord.

    PubMed

    Hadas, Yoav; Nitzan, Noa; Furley, Andrew J W; Kozlov, Serguei V; Klar, Avihu

    2013-01-01

    Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1) and Neurofascin (Nfasc) are co-expressed in numerous neuronal cell types in the CNS and PNS - for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 5' to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system.

  16. Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis.

    PubMed

    Gato, Angel; Desmond, Mary E

    2009-03-15

    The key focus of this review is that both the neuroepithelium and embryonic cerebrospinal fluid (CSF) work in an integrated way to promote embryonic brain growth, morphogenesis and histiogenesis. The CSF generates pressure and also contains many biologically powerful trophic factors; both play key roles in early brain development. Accumulation of fluid via an osmotic gradient creates pressure that promotes rapid expansion of the early brain in a developmental regulated way, since the rates of growth differ between the vesicles and for different species. The neuroepithelium and ventricles both contribute to this growth but by different and coordinated mechanisms. The neuroepithelium grows primarily by cell proliferation and at the same time the ventricle expands via hydrostatic pressure generated by active transport of Na(+) and transport or secretion of proteins and proteoglycans that create an osmotic gradient which contribute to the accumulation of fluid inside the sealed brain cavity. Recent evidence shows that the CSF regulates relevant aspects of neuroepithelial behavior such as cell survival, replication and neurogenesis by means of growth factors and morphogens. Here we try to highlight that early brain development requires the coordinated interplay of the CSF contained in the brain cavity with the surrounding neuroepithelium. The information presented is essential in order to understand the earliest phases of brain development and also how neuronal precursor behavior is regulated.

  17. All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development.

    PubMed

    Parada, Carolina; Gato, Angel; Bueno, David

    2008-06-11

    Embryonic cerebrospinal fluid (E-CSF) is involved in the regulation of survival, proliferation and neurogenesis of neuroectodermal progenitor cells, as well as in the control of mesencephalic gene expression in collaboration with the isthmic organizer. Recently, we showed the presence of retinol-binding protein (RBP) within the E-CSF proteome. RBP is an all-trans retinol carrier, a molecule that can be metabolized into retinoic acid, a morphogen involved in central nervous system (CNS) morphogenesis and patterning. Here we demonstrate the presence of all-trans retinol within the E-CSF and analyse the dynamics of RBP and all-trans retinol within this fluid, as well as the expression of retinoic acid-synthesizing enzymes during early CNS development. Our results suggest a relationship between the dynamics of these molecules and the early events of CNS patterning. PMID:18520998

  18. Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model''

    SciTech Connect

    Dmitriy Y. Anistratov; Marvin L. Adams; Todd S. Palmer; Kord S. Smith; Kevin Clarno; Hikaru Hiruta; Razvan Nes

    2003-08-04

    OAK (B204) Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model'' The present generation of reactor analysis methods uses few-group nodal diffusion approximations to calculate full-core eigenvalues and power distributions. The cross sections, diffusion coefficients, and discontinuity factors (collectively called ''group constants'') in the nodal diffusion equations are parameterized as functions of many variables, ranging from the obvious (temperature, boron concentration, etc.) to the more obscure (spectral index, moderator temperature history, etc.). These group constants, and their variations as functions of the many variables, are calculated by assembly-level transport codes. The current methodology has two main weaknesses that this project addressed. The first weakness is the diffusion approximation in the full-core calculation; this can be significantly inaccurate at interfaces between different assemblies. This project used the nodal diffusion framework to implement nodal quasidiffusion equations, which can capture transport effects to an arbitrary degree of accuracy. The second weakness is in the parameterization of the group constants; current models do not always perform well, especially at interfaces between unlike assemblies. The project developed a theoretical foundation for parameterization and homogenization models and used that theory to devise improved models. The new models were extended to tabulate information that the nodal quasidiffusion equations can use to capture transport effects in full-core calculations.

  19. High Risk of Lateral Nodal Metastasis in Lateral Solitary Solid Papillary Thyroid Cancer.

    PubMed

    Lai, Xing-Jian; Zhang, Bo; Jiang, Yu-Xin; Li, Jian-Chu; Zhao, Rui-Na; Yang, Xiao; Zhang, Qing; Zhang, Xiao-Yan; Li, Wen-Bo; Zhu, Shen-Ling

    2016-01-01

    We explored the relationship between ultrasonic intra-thyroidal location and neck node metastasis pattern in solitary solid papillary thyroid cancer (PTC). Data on 186 patients were retrospectively reviewed. The association between several characteristics and neck node metastasis pattern were analyzed. Among the 186 thyroid nodules, age ≥45 y (p = 0.005), mass size ≥2 cm (p = 0.001), presence of calcifications (p < 0.001) and lateral nodal metastasis (p = 0.001) were significantly related to central nodal metastasis in multivariate analysis. Mass size ≥2 cm (p = 0.046) and central nodal metastasis (p = 0.002) were significantly related to lateral nodal metastasis in multivariate analysis. Location of an intra-thyroidal solitary solid PTC located non-adjacent to the trachea (lateral) was significantly related to lateral nodal metastasis (p = 0.043) compared with location of an intra-thyroidal solitary solid PTC adjacent to the trachea (medial or isthmus). Lateral lesions have a high risk of lateral nodal metastasis in solitary solid PTC.

  20. Undertreatment of patients with localized extranodal compared with nodal diffuse large B-cell lymphoma.

    PubMed

    Kuper-Hommel, Marion J J; van de Schans, Saskia A M; Vreugdenhil, Gerard; van Krieken, J Han; Coebergh, Jan-Willem W

    2013-08-01

    Population-based studies analyzing clinical implications of nodal versus extranodal (EN) presentation of diffuse large B-cell lymphoma (DLBCL) are scarce. We studied clinical differences and trends in incidence, treatment and survival of nodal and EN DLBCL in a population-based cohort. All patients newly diagnosed with localized (Ann Arbor stage [AAS] I and II) nodal (n = 5124) and EN (n = 4776) DLBCL, and primary mediastinal B-cell lymphoma (PMBL; n = 88), diagnosed between 1989 and 2010, were selected from the Netherlands Cancer Registry. Primary EN disease was correlated with older age and more favorable clinical stage (AAS I). The age standardized incidence rates for men with localized EN DLBCL, and for men and women with localized PMBL, increased significantly, whereas the age standardized incidence rates of all other subgroups remained stable. The stomach was the most common EN localization. Patients with EN disease received less chemotherapy and targeted therapy than their nodal counterparts, irrespective of age and period of diagnosis. Their 5-year overall survival (OS) was 48% vs. 54% in the nodal group, but in multivariate analysis primary extranodal presentation was not independently associated with inferior survival. This population-based study shows clinically relevant differences between localized nodal and EN DLBCL and PMBL. Since patients with EN were significantly less often optimally treated, we advocate better interaction between medical disciplines. PMID:23190406

  1. Solution and Study of the Two-Dimensional Nodal Neutron Transport Equation

    SciTech Connect

    Panta Pazos, Ruben; Biasotto Hauser, Eliete; Tullio de Vilhena, Marco

    2002-07-01

    In the last decade Vilhena and coworkers reported an analytical solution to the two-dimensional nodal discrete-ordinates approximations of the neutron transport equation in a convex domain. The key feature of these works was the application of the combined collocation method of the angular variable and nodal approach in the spatial variables. By nodal approach we mean the transverse integration of the SN equations. This procedure leads to a set of one-dimensional S{sub N} equations for the average angular fluxes in the variables x and y. These equations were solved by the old version of the LTS{sub N} method, which consists in the application of the Laplace transform to the set of nodal S{sub N} equations and solution of the resulting linear system by symbolic computation. It is important to recall that this procedure allow us to increase N the order of S{sub N} up to 16. To overcome this drawback we step forward performing a spectral painstaking analysis of the nodal S{sub N} equations for N up to 16 and we begin the convergence of the S{sub N} nodal equations defining an error for the angular flux and estimating the error in terms of the truncation error of the quadrature approximations of the integral term. Furthermore, we compare numerical results of this approach with those of other techniques used to solve the two-dimensional discrete approximations of the neutron transport equation. (authors)

  2. A quasi-static polynomial nodal method for nuclear reactor analysis

    SciTech Connect

    Gehin, J.C.

    1992-09-01

    Modern nodal methods are currently available which can accurately and efficiently solve the static and transient neutron diffusion equations. Most of the methods, however, are limited to two energy groups for practical application. The objective of this research is the development of a static and transient, multidimensional nodal method which allows more than two energy groups and uses a non-linear iterative method for efficient solution of the nodal equations. For both the static and transient methods, finite-difference equations which are corrected by the use of discontinuity factors are derived. The discontinuity factors are computed from a polynomial nodal method using a non-linear iteration technique. The polynomial nodal method is based upon a quartic approximation and utilizes a quadratic transverse-leakage approximation. The solution of the time-dependent equations is performed by the use of a quasi-static method in which the node-averaged fluxes are factored into shape and amplitude functions. The application of the quasi-static polynomial method to several benchmark problems demonstrates that the accuracy is consistent with that of other nodal methods. The use of the quasi-static method is shown to substantially reduce the computation time over the traditional fully-implicit time-integration method. Problems involving thermal-hydraulic feedback are accurately, and efficiently, solved by performing several reactivity/thermal-hydraulic updates per shape calculation.

  3. The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development

    PubMed Central

    Deshwar, Ashish R; Chng, Serene C; Ho, Lena; Reversade, Bruno; Scott, Ian C

    2016-01-01

    The Apelin receptor (Aplnr) is essential for heart development, controlling the early migration of cardiac progenitors. Here we demonstrate that in zebrafish Aplnr modulates Nodal/TGFβ signaling, a key pathway essential for mesendoderm induction and migration. Loss of Aplnr function leads to a reduction in Nodal target gene expression whereas activation of Aplnr by a non-peptide agonist increases the expression of these same targets. Furthermore, loss of Aplnr results in a delay in the expression of the cardiogenic transcription factors mespaa/ab. Elevating Nodal levels in aplnra/b morphant and double mutant embryos is sufficient to rescue cardiac differentiation defects. We demonstrate that loss of Aplnr attenuates the activity of a point source of Nodal ligands Squint and Cyclops in a non-cell autonomous manner. Our results favour a model in which Aplnr is required to fine-tune Nodal output, acting as a specific rheostat for the Nodal/TGFβ pathway during the earliest stages of cardiogenesis. DOI: http://dx.doi.org/10.7554/eLife.13758.001 PMID:27077952

  4. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

    SciTech Connect

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin; Wang, Guan-song; Belguise, Karine; Wang, Xiaobo; Qian, Gui-sheng; Lu, Kai-zhi; Yi, Bin

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

  5. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    SciTech Connect

    Sun, Jing; Liu, Su-zhi; Lin, Yan; Cao, Xiao-pan; Liu, Jia-ming

    2014-01-17

    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significant when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.

  6. Embryonic Stem Cell Growth Factors Regulate eIF2α Phosphorylation.

    PubMed

    Friend, Kyle; Brooks, Hunter A; Propson, Nicholas E; Thomson, James A; Kimble, Judith

    2015-01-01

    Growth factors and transcription factors are well known to regulate pluripotent stem cells, but less is known about translational control in stem cells. Here, we use embryonic stem cells (ESCs) to investigate a connection between ESC growth factors and eIF2α-mediated translational control (eIF2α phosphorylation promotes protein expression from mRNAs with upstream open-reading frames, or uORFs). We find abundant phosphorylated P-eIF2α (P-eIF2α) in both pluripotent mouse and human ESCs, but little P-eIF2α in ESCs triggered to differentiate. We show that the growth factors LIF (leukemia inhibitory factor) and BMP4 (bone morphogenic protein 4) both maintain P-eIF2α in mESCs, but use distinct mechanisms: LIF inhibits an eIF2α phosphatase whereas BMP4 activates an eIF2α kinase. The mRNAs encoding the pluripotency factors Nanog and c-Myc possess uORFs while Oct4 mRNA does not. We find that salubrinal, a chemical that increases eIF2α phosphorylation, promotes Nanog and c-Myc expression, but not Oct4 expression. These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression. PMID:26406898

  7. Embryonic Stem Cell Growth Factors Regulate eIF2α Phosphorylation

    PubMed Central

    Friend, Kyle; Brooks, Hunter A.; Propson, Nicholas E.; Thomson, James A.; Kimble, Judith

    2015-01-01

    Growth factors and transcription factors are well known to regulate pluripotent stem cells, but less is known about translational control in stem cells. Here, we use embryonic stem cells (ESCs) to investigate a connection between ESC growth factors and eIF2α-mediated translational control (eIF2α phosphorylation promotes protein expression from mRNAs with upstream open-reading frames, or uORFs). We find abundant phosphorylated P-eIF2α (P-eIF2α) in both pluripotent mouse and human ESCs, but little P-eIF2α in ESCs triggered to differentiate. We show that the growth factors LIF (leukemia inhibitory factor) and BMP4 (bone morphogenic protein 4) both maintain P-eIF2α in mESCs, but use distinct mechanisms: LIF inhibits an eIF2α phosphatase whereas BMP4 activates an eIF2α kinase. The mRNAs encoding the pluripotency factors Nanog and c-Myc possess uORFs while Oct4 mRNA does not. We find that salubrinal, a chemical that increases eIF2α phosphorylation, promotes Nanog and c-Myc expression, but not Oct4 expression. These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression. PMID:26406898

  8. Coexistent Types of Atrioventricular Nodal Re-Entrant Tachycardia

    PubMed Central

    Marine, Joseph E.; Latchamsetty, Rakesh; Zografos, Theodoros; Tanawuttiwat, Tanyanan; Sheldon, Seth H.; Buxton, Alfred E.; Calkins, Hugh; Morady, Fred; Josephson, Mark E.

    2015-01-01

    Background— There is evidence that atypical fast–slow and typical atrioventricular nodal re-entrant tachycardia (AVNRT) do not use the same limb for fast conduction, but no data exist on patients who have presented with both typical and atypical forms of this tachycardia. We compared conduction intervals during typical and atypical AVNRT that occurred in the same patient. Methods and Results— In 20 of 1299 patients with AVNRT, both typical and atypical AVNRT were induced at electrophysiology study by pacing maneuvers and autonomic stimulation or occurred spontaneously. The mean age of the patients was 47.6±10.9 years (range, 32–75 years), and 11 patients (55%) were women. Tachycardia cycle lengths were 368.0±43.1 and 365.8±41.1 ms, and earliest retrograde activation was recorded at the coronary sinus ostium in 60% and 65% of patients with typical and atypical AVNRT, respectively. Thirteen patients (65%) displayed atypical AVNRT with fast–slow characteristics. By comparing conduction intervals during slow–fast and fast–slow AVNRT in the same patient, fast pathway conduction times during the 2 types of AVNRT were calculated. The mean difference between retrograde fast pathway conduction during slow–fast AVNRT and anterograde fast pathway conduction during fast–slow AVNRT was 41.8±39.7 ms and was significantly different when compared with the estimated between-measurement error (P=0.0055). Conclusions— Our data provide further evidence that typical slow–fast and atypical fast–slow AVNRT use different anatomic pathways for fast conduction. PMID:26155802

  9. Cluster analysis of contaminated sediment data: nodal analysis.

    PubMed

    Hartwell, S Ian; Claflin, Larry W

    2005-07-01

    The objective of the present study was to explore the use of multivariate statistical methods as a means to discern relationships between contaminants and biological and/or toxicological effects in a representative data set from the National Status and Trends (NS&T) Program. Data from the National Oceanic and Atmospheric Administration, NS&T Program's Bioeffects Survey of Delaware Bay, USA, were examined using various univariate and multivariate statistical techniques, including cluster analysis. Each approach identified consistent patterns and relationships between the three types of triad data. The analyses also identified factors that bias the interpretation of the data, primarily the presence of rare and unique species and the dependence of species distributions on physical parameters. Sites and species were clustered with the unweighted pair-group method using arithmetic averages clustering with the Jaccard coefficient that clustered species and sites into mutually consistent groupings. Pearson product moment correlation coefficients, normalized for salinity, also were clustered. The most informative analysis, termed nodal analysis, was the intersection of species cluster analysis with site cluster analysis. This technique produced a visual representation of species association patterns among site clusters. Site characteristics, such as salinity and grain size, not contaminant concentrations, appeared to be the primary factors determining species distributions. This suggests the sediment-quality triad needs to use physical parameters as a distinct leg from chemical concentrations to improve sediment-quality assessments in large bodies of water. Because the Delaware Bay system has confounded gradients of contaminants and physical parameters, analyses were repeated with data from northern Chesapeake Bay, USA, with similar results. PMID:16050601

  10. Prepatterning and patterning of the thalamus along embryonic development of Xenopus laevis

    PubMed Central

    Bandín, Sandra; Morona, Ruth; González, Agustín

    2015-01-01

    Previous developmental studies of the thalamus (alar part of the diencephalic prosomere p2) have defined the molecular basis for the acquisition of the thalamic competence (preparttening), the subsequent formation of the secondary organizer in the zona limitans intrathalamica, and the early specification of two anteroposterior domains (rostral and caudal progenitor domains) in response to inducing activities and that are shared in birds and mammals. In the present study we have analyzed the embryonic development of the thalamus in the anuran Xenopus laevis to determine conserved or specific features in the amphibian diencephalon. From early embryonic stages to the beginning of the larval period, the expression patterns of 22 markers were analyzed by means of combined In situ hybridization (ISH) and immunohistochemical techniques. The early genoarchitecture observed in the diencephalon allowed us to discern the boundaries of the thalamus with the prethalamus, pretectum, and epithalamus. Common molecular features were observed in the thalamic prepatterning among vertebrates in which Wnt3a, Fez, Pax6 and Xiro1 expression were of particular importance in Xenopus. The formation of the zona limitans intrathalamica was observed, as in other vertebrates, by the progressive expression of Shh. The largely conserved expressions of Nkx2.2 in the rostral thalamic domain vs. Gbx2 and Ngn2 (among others) in the caudal domain strongly suggest the role of Shh as morphogen in the amphibian thalamus. All these data showed that the molecular characteristics observed during preparttening and patterning in the thalamus of the anuran Xenopus (anamniote) share many features with those described during thalamic development in amniotes (common patterns in tetrapods) but also with zebrafish, strengthening the idea of a basic organization of this diencephalic region across vertebrates. PMID:26321920

  11. Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

    PubMed Central

    Seol, Ki Ho

    2016-01-01

    Purpose To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Materials and Methods Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4–72 Gy (39.6–45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. Results The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. Conclusion No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC. PMID:27104162

  12. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency.

    PubMed

    Fiorenzano, Alessandro; Pascale, Emilia; D'Aniello, Cristina; Acampora, Dario; Bassalert, Cecilia; Russo, Francesco; Andolfi, Gennaro; Biffoni, Mauro; Francescangeli, Federica; Zeuner, Ann; Angelini, Claudia; Chazaud, Claire; Patriarca, Eduardo J; Fico, Annalisa; Minchiotti, Gabriella

    2016-01-01

    Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo. PMID:27586544

  13. Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency

    PubMed Central

    Fiorenzano, Alessandro; Pascale, Emilia; D'Aniello, Cristina; Acampora, Dario; Bassalert, Cecilia; Russo, Francesco; Andolfi, Gennaro; Biffoni, Mauro; Francescangeli, Federica; Zeuner, Ann; Angelini, Claudia; Chazaud, Claire; Patriarca, Eduardo J.; Fico, Annalisa; Minchiotti, Gabriella

    2016-01-01

    Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/β-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo. PMID:27586544

  14. The dynein-triggered ciliary motion in embryonic nodes: an exploratory study based on computational models.

    PubMed

    Chen, Duanduan; Zhong, Yi; Shinohara, Kyosuke; Nishida, Tomoki; Hasegawa, Toshiaki; Hamada, Hiroshi

    2014-01-01

    The cilia, presenting a rotational movement in the embryonic nodes, play a crucial role in the left-right specification during embryogenesis. The characteristic architecture of these cilia is based on a cylindrical arrangement of 9 doublet microtubules and the motion of the cilia is triggered by the dynein motors located between adjacent doublets by converting the chemical energy into mechanical work. Restricted by the inherent difficulties of experiments, the dynein activation patterns in moving cilia cannot be directly observed. Thus, the mechanism of nodal ciliary movement is still unclear. In this study, we present computational models of the nodal ciliary ultrastructure based on tomographic images of the ciliary body. By employing time accurate three-dimensional solid mechanics analysis, we investigate the dynein-triggered sliding between adjacent doublet microtubules and simulate the induced ciliary bending. As an exploratory study, two dynein activation patterns are proposed and their rationality is discussed. The mathematical model presented by this paper provides a platform to investigate various assumptions of dynein activity, facilitating us to propose the most possible dynein activation pattern and therefore improving our understandings regarding the protein-beating problems of cilia.

  15. Topological nodal-line fermions in spin-orbit metal PbTaSe2.

    PubMed

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M Zahid

    2016-02-02

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.

  16. Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

    PubMed Central

    van den Brand, Michiel; van Krieken, J. Han J.M.

    2013-01-01

    The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity. PMID:23813646

  17. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    DOE PAGESBeta

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; et al

    2016-02-02

    Here we discuss how topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterizedmore » by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.« less

  18. Topological nodal-line fermions in spin-orbit metal PbTaSe2.

    PubMed

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M Zahid

    2016-01-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID:26829889

  19. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    NASA Astrophysics Data System (ADS)

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S.; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, Baokai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M. Zahid

    2016-02-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.

  20. Auxin controls local cytokinin biosynthesis in the nodal stem in apical dominance.

    PubMed

    Tanaka, Mina; Takei, Kentaro; Kojima, Mikiko; Sakakibara, Hitoshi; Mori, Hitoshi

    2006-03-01

    In intact plants, the shoot apex grows predominantly and inhibits outgrowth of axillary buds. After decapitation of the shoot apex, outgrowth of axillary buds begins. This phenomenon is called an apical dominance. Although the involvement of auxin, which represses outgrowth of axillary buds, and cytokinin (CK), which promotes outgrowth of axillary buds, has been proposed, little is known about the underlying molecular mechanisms. In the present study, we demonstrated that auxin negatively regulates local CK biosynthesis in the nodal stem by controlling the expression level of the pea (Pisum sativum L.) gene adenosine phosphate-isopentenyltransferase (PsIPT), which encodes a key enzyme in CK biosynthesis. Before decapitation, PsIPT1 and PsIPT2 transcripts were undetectable; after decapitation, they were markedly induced in the nodal stem along with accumulation of CK. Expression of PsIPT was repressed by the application of indole-3-acetic acid (IAA). In excised nodal stem, PsIPT expression and CK levels also increased under IAA-free conditions. Furthermore, beta-glucuronidase expression, under the control of the PsIPT2 promoter region in transgenic Arabidopsis, was repressed by an IAA. Our results indicate that in apical dominance one role of auxin is to repress local biosynthesis of CK in the nodal stem and that, after decapitation, CKs, which are thought to be derived from the roots, are locally biosynthesized in the nodal stem rather than in the roots. PMID:16507092

  1. Temporal and spatial requirements for Nodal-induced anterior mesendoderm and mesoderm in anterior neurulation.

    PubMed

    Gonsar, Ngawang; Coughlin, Alicia; Clay-Wright, Jessica A; Borg, Bethanie R; Kindt, Lexy M; Liang, Jennifer O

    2016-01-01

    Zebrafish with defective Nodal signaling have a phenotype analogous to the fatal human birth defect anencephaly, which is caused by an open anterior neural tube. Previous work in our laboratory found that anterior open neural tube phenotypes in Nodal signaling mutants were caused by lack of mesendodermal/mesodermal tissues. Defects in these mutants are already apparent at neural plate stage, before the neuroepithelium starts to fold into a tube. Consistent with this, we found that the requirement for Nodal signaling maps to mid-late blastula stages. This timing correlates with the timing of prechordal plate mesendoderm and anterior mesoderm induction, suggesting these tissues act to promote neurulation. To further identify tissues important for neurulation, we took advantage of the variable phenotypes in Nodal signaling-deficient sqt mutant and Lefty1-overexpressing embryos. Statistical analysis indicated a strong, positive correlation between a closed neural tube and presence of several mesendoderm/mesoderm-derived tissues (hatching glands, cephalic paraxial mesoderm, notochord, and head muscles). However, the neural tube was closed in a subset of embryos that lacked any one of these tissues. This suggests that several types of Nodal-induced mesendodermal/mesodermal precursors are competent to promote neurulation. PMID:26528772

  2. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    PubMed Central

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S.; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M. Zahid

    2016-01-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID:26829889

  3. Temporal and spatial requirements for Nodal-induced anterior mesendoderm and mesoderm in anterior neurulation.

    PubMed

    Gonsar, Ngawang; Coughlin, Alicia; Clay-Wright, Jessica A; Borg, Bethanie R; Kindt, Lexy M; Liang, Jennifer O

    2016-01-01

    Zebrafish with defective Nodal signaling have a phenotype analogous to the fatal human birth defect anencephaly, which is caused by an open anterior neural tube. Previous work in our laboratory found that anterior open neural tube phenotypes in Nodal signaling mutants were caused by lack of mesendodermal/mesodermal tissues. Defects in these mutants are already apparent at neural plate stage, before the neuroepithelium starts to fold into a tube. Consistent with this, we found that the requirement for Nodal signaling maps to mid-late blastula stages. This timing correlates with the timing of prechordal plate mesendoderm and anterior mesoderm induction, suggesting these tissues act to promote neurulation. To further identify tissues important for neurulation, we took advantage of the variable phenotypes in Nodal signaling-deficient sqt mutant and Lefty1-overexpressing embryos. Statistical analysis indicated a strong, positive correlation between a closed neural tube and presence of several mesendoderm/mesoderm-derived tissues (hatching glands, cephalic paraxial mesoderm, notochord, and head muscles). However, the neural tube was closed in a subset of embryos that lacked any one of these tissues. This suggests that several types of Nodal-induced mesendodermal/mesodermal precursors are competent to promote neurulation.

  4. Entrainment mapping in patients with sustained atrioventricular nodal reentrant tachycardia: insights into the sites of conduction slowing in the slow atrioventricular nodal pathway.

    PubMed

    Haines, D E; Nath, S; DiMarco, J P; Lobban, J H

    1997-10-01

    The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or

  5. Culture and Manipulation of Embryonic Cells

    PubMed Central

    Edgar, Lois G.; Goldstein, Bob

    2012-01-01

    The direct manipulation of embryonic cells is an important tool for addressing key questions in cell and developmental biology. C. elegans is relatively unique among genetic model systems in being amenable to manipulation of embryonic cells. Embryonic cell manipulation has allowed the identification of cell interactions by direct means, and it has been an important technique for dissecting mechanisms by which cell fates are specified, cell divisions are oriented, and morphogenesis is accomplished. Here, we present detailed methods for isolating, manipulating and culturing embryonic cells of C. elegans. PMID:22226523

  6. [Epigenetic influence on embryonic development].

    PubMed

    Donkin, Ida; Barrès, Romain; Pinborg, Anja

    2016-09-12

    The epigenome is sensitive to environmental changes and can sustainably alter gene expression, notably during embryonic development. New research indicates that epigenetic factors are heritable, which is why paternal lifestyle may affect fetal development and risk of disease. Children conceived by assisted reproduction technology (ART) have an increased risk of peri- and postnatal complications, and as specific ART protocols associate with specific risk profiles, the procedures themselves may cause epigenetic changes contributing to the altered outcomes of the 5,000 Danish children annually conceived by ART. PMID:27649584

  7. Zebrafish Rab5 proteins and a role for Rab5ab in nodal signalling

    PubMed Central

    Kenyon, Emma J.; Campos, Isabel; Bull, James C.; Williams, P. Huw; Stemple, Derek L.; Clark, Matthew D.

    2015-01-01

    The RAB5 gene family is the best characterised of all human RAB families and is essential for in vitro homotypic fusion of early endosomes. In recent years, the disruption or activation of Rab5 family proteins has been used as a tool to understand growth factor signal transduction in whole animal systems such as Drosophila melanogaster and zebrafish. In this study we have examined the functions for four rab5 genes in zebrafish. Disruption of rab5ab expression by antisense morpholino oligonucleotide (MO) knockdown abolishes nodal signalling in early zebrafish embryos, whereas overexpression of rab5ab mRNA leads to ectopic expression of markers that are normally downstream of nodal signalling. By contrast MO disruption of other zebrafish rab5 genes shows little or no effect on expression of markers of dorsal organiser development. We conclude that rab5ab is essential for nodal signalling and organizer specification in the developing zebrafish embryo. PMID:25478908

  8. Zebrafish Rab5 proteins and a role for Rab5ab in nodal signalling.

    PubMed

    Kenyon, Emma J; Campos, Isabel; Bull, James C; Williams, P Huw; Stemple, Derek L; Clark, Matthew D

    2015-01-15

    The RAB5 gene family is the best characterised of all human RAB families and is essential for in vitro homotypic fusion of early endosomes. In recent years, the disruption or activation of Rab5 family proteins has been used as a tool to understand growth factor signal transduction in whole animal systems such as Drosophila melanogaster and zebrafish. In this study we have examined the functions for four rab5 genes in zebrafish. Disruption of rab5ab expression by antisense morpholino oligonucleotide (MO) knockdown abolishes nodal signalling in early zebrafish embryos, whereas overexpression of rab5ab mRNA leads to ectopic expression of markers that are normally downstream of nodal signalling. By contrast MO disruption of other zebrafish rab5 genes shows little or no effect on expression of markers of dorsal organiser development. We conclude that rab5ab is essential for nodal signalling and organizer specification in the developing zebrafish embryo.

  9. Molecular organization of the nodal region is not altered in spontaneously diabetic BB-Wistar rats.

    PubMed

    Brown, A A; Xu, T; Arroyo, E J; Levinson, S R; Brophy, P J; Peles, E; Scherer, S S

    2001-07-15

    We examined the organization of the molecular components of the nodal region in spontaneously diabetic BB-Wistar rats. Frozen sections and teased fibers from the sciatic nerves were immunostained for nodal (voltage-gated Na(+) channels, ankyrin(G), and ezrin), paranodal (contactin, Caspr, and neurofascin 155 kDa), and juxtaparanodal (Caspr2, the Shaker-type K(+) channels Kv1.1 and Kv1.2, and their associated subunit Kvbeta2) proteins. All of these proteins were properly localized in myelinated fibers from rats that had been diabetic for 15-44 days, compared to age-matched, nondiabetic animals. These results demonstrate that the axonal membrane is not reorganized, so nodal reorganization is not likely to be the cause of nerve conduction slowing in this animal model of acute diabetes. PMID:11438983

  10. Interaction of pupil offset and fifth-order nodal aberration field properties in rotationally symmetric telescopes.

    PubMed

    Hu, Haili; Liu, Jianjun; Fan, Zhigang

    2013-07-29

    In this paper we succeeded in deriving changes in the nodal positions of aberrations that belong to the fifth-order class in pupil dependence by applying a system level pupil decentration vector. Our treatment is specifically for rotationally symmetric multi-mirror optical designs that simply use an offset pupil as a means of creating an unobscured optical design. When the pupil is offset, only the vectors to determine the node locations are modified by the pupil decentration vector, while the nodal properties originally developed for titled/decentered optical systems are retained. In general, the modifications to the nodal vectors for any particular aberration type are contributed only by terms of higher order pupil dependence.

  11. Melanocytes Affect Nodal Expression and Signaling in Melanoma Cells: A Lesson from Pediatric Large Congenital Melanocytic Nevi

    PubMed Central

    Margaryan, Naira V.; Gilgur, Alina; Seftor, Elisabeth A.; Purnell, Chad; Arva, Nicoleta C.; Gosain, Arun K.; Hendrix, Mary J. C.; Strizzi, Luigi

    2016-01-01

    Expression of Nodal, a Transforming Growth Factor-beta (TGF-β) related growth factor, is associated with aggressive melanoma. Nodal expression in adult dysplastic nevi may predict the development of aggressive melanoma in some patients. A subset of pediatric patients diagnosed with giant or large congenital melanocytic nevi (LCMN) has shown increased risk for development of melanoma. Here, we investigate whether Nodal expression can help identify the rare cases of LCMN that develop melanoma and shed light on why the majority of these patients do not. Immunohistochemistry (IHC) staining results show varying degree of Nodal expression in pediatric dysplastic nevi and LCMN. Moreover, median scores from Nodal IHC expression analysis were not significantly different between these two groups. Additionally, none of the LCMN patients in this study developed melanoma, regardless of Nodal IHC levels. Co-culture experiments revealed reduced tumor growth and lower levels of Nodal and its signaling molecules P-SMAD2 and P-ERK1/2 when melanoma cells were grown in vivo or in vitro with normal melanocytes. The same was observed in melanoma cells cultured with melanocyte conditioned media containing pigmented melanocyte derived melanosomes (MDM). Since MDM contain molecules capable of inactivating radical oxygen species, to investigate potential anti-oxidant effect of MDM on Nodal expression and signaling in melanoma, melanoma cells were treated with either N-acetyl-l-cysteine (NAC), a component of the anti-oxidant glutathione or synthetic melanin, which in addition to providing pigmentation can also exert free radical scavenging activity. Melanoma cells treated with NAC or synthetic melanin showed reduced levels of Nodal, P-SMAD2 and P-ERK1/2 compared to untreated melanoma cells. Thus, the potential role for Nodal in melanoma development in LCMN is less evident than in adult dysplastic nevi possibly due to melanocyte cross-talk in LCMN capable of offsetting or delaying the pro

  12. Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast Cancer: The Impact of Cortical Thickness

    PubMed Central

    Stachs, A.; Thi, A. Tra-Ha; Dieterich, M.; Stubert, J.; Hartmann, S.; Glass, Ä.; Reimer, T.; Gerber, B.

    2015-01-01

    Purpose: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal metastasis in patients with early-stage breast cancer and to identify AUS features with high predictive power. Materials and Methods: Prospective single-center preliminary study in 105 patients with a primary diagnosis of breast cancer and clinically negative axilla. AUS was performed using a 12 MHz linear-array transducer before ultrasound-guided needle biopsy. Nodal characteristics (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness, hyperechoic hilum) were correlated with histopathological nodal status after SLNB or axillary lymph node dissection (ALND). Results: Nodal metastases were present in 42/105 patients (40.0%). Univariate analyses showed that absence of hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical thickness>3 mm were associated with lymph node metastasis. Multivariate logistic regression analysis revealed cortical thickness > 3 mm as an independent predictive parameter for nodal involvement. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6, 77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the criterion for AUS positivity. Axillary tumor volume was low in patients with pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic lymph nodes. Conclusion: Cortical thickness>3 mm is a reliable predictor of nodal metastatic involvement. Negative AUS does not exclude lymph node metastases, but extensive axillary tumor volume is rare.

  13. A predictive index of axillary nodal involvement in operable breast cancer.

    PubMed Central

    De Laurentiis, M.; Gallo, C.; De Placido, S.; Perrone, F.; Pettinato, G.; Petrella, G.; Carlomagno, C.; Panico, L.; Delrio, P.; Bianco, A. R.

    1996-01-01

    We investigated the association between pathological characteristics of primary breast cancer and degree of axillary nodal involvement and obtained a predictive index of the latter from the former. In 2076 cases, 17 histological features, including primary tumour and local invasion variables, were recorded. The whole sample was randomly split in a training (75% of cases) and a test sample. Simple and multiple correspondence analysis were used to select the variables to enter in a multinomial logit model to build an index predictive of the degree of nodal involvement. The response variable was axillary nodal status coded in four classes (N0, N1-3, N4-9, N > or = 10). The predictive index was then evaluated by testing goodness-of-fit and classification accuracy. Covariates significantly associated with nodal status were tumour size (P < 0.0001), tumour type (P < 0.0001), type of border (P = 0.048), multicentricity (P = 0.003), invasion of lymphatic and blood vessels (P < 0.0001) and nipple invasion (P = 0.006). Goodness-of-fit was validated by high concordance between observed and expected number of cases in each decile of predicted probability in both training and test samples. Classification accuracy analysis showed that true node-positive cases were well recognised (84.5%), but there was no clear distinction among the classes of node-positive cases. However, 10 year survival analysis showed a superimposible prognostic behaviour between predicted and observed nodal classes. Moreover, misclassified node-negative patients (i.e. those who are predicted positive) showed an outcome closer to patients with 1-3 metastatic nodes than to node-negative ones. In conclusion, the index cannot completely substitute for axillary node information, but it is a predictor of prognosis as accurate as nodal involvement and identifies a subgroup of node-negative patients with unfavourable prognosis. PMID:8630286

  14. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    SciTech Connect

    Lao, Louis; Hope, Andrew J.; Maganti, Manjula; Brade, Anthony; Bezjak, Andrea; Saibishkumar, Elantholi P.; Giuliani, Meredith; Sun, Alexander; Cho, B. C. John

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

  15. CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture.

    PubMed

    Kirshner, Julia; Chen, Charng-Jui; Liu, Pingfang; Huang, Jie; Shively, John E

    2003-01-21

    In a 3D model of breast morphogenesis, CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) plays an essential role in lumen formation in a subline of the nonmalignant human breast cell line (MCF10A). We show that mammary carcinoma cells (MCF7), which do not express CEACAM1 or form lumena when grown in Matrigel, are restored to a normal morphogenic program when transfected with CEACAM1-4S, the short cytoplasmic isoform of CEACAM1 that predominates in breast epithelia. During the time course of lumen formation, CEACAM1-4S was found initially between the cells, and in mature acini, it was found exclusively in an apical location, identical to its expression pattern in normal breast. Lumena were formed by apoptosis as opposed to necrosis of the central cells within the alveolar structures, and apoptotic cells within the lumena expressed CEACAM1-4S. Dying cells exhibited classical hallmarks of apoptosis, including nuclear condensation, membrane blebbing, caspase activation, and DNA laddering. Apoptosis was mediated by Bax translocation to the mitochondria and release of cytochrome c into the cytoplasm, and was partially inhibited by culturing cells with caspase inhibitors. The dynamic changes in CEACAM1 expression during morphogenesis, together with studies implicating extracellular matrix and integrin signaling, suggest that a morphogenic program integrates cell-cell and cell-extracellular matrix signaling to produce the lumena in mammary glands. This report reveals a function of CEACAM1-4S relevant to cellular physiology that distinguishes it from its related long cytoplasmic domain isoform.

  16. Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements

    PubMed Central

    Norris, Dominic P.; Robertson, Elizabeth J.

    1999-01-01

    The TGFβ-related molecule Nodal is required for establishment of the anterior–posterior (A–P) and left–right (L-R) body axes of the vertebrate embryo. In mouse, several discrete sites of nodal activity closely correlate with its highly dynamic expression domains. nodal function in the posterior epiblast promotes primitive streak formation, whereas transient nodal expression in the extraembryonic visceral endoderm is essential for patterning the rostral central nervous system. Asymmetric nodal expression in the developing node and at later stages in left lateral plate mesoderm has been implicated as a key regulator of L-R axis determination. We have analyzed the cis-regulatory elements controlling nodal expression domains during early development. We show that the regulatory sequences conferring node-specific expression are contained in an upstream region of the locus, whereas early expression in the endoderm and epiblast and asymmetric expression at later stages on the left side of the body axis are controlled by a 600-bp intronic enhancer. Targeted deletion of a 100-bp subregion of this intronic enhancer eliminates nodal expression in the early epiblast and visceral endoderm and disrupts asymmetric expression in the node and lateral plate mesoderm. Thus, developmentally regulated nodal expression at distinct tissue sites during A–P and L-R axis formation is potentially controlled by common transcriptional activators. PMID:10385626

  17. Nodal Quasiparticle Meltdown in Ultra-High Resolution Pump-Probe Angle-Resolved Photoemission

    SciTech Connect

    Graf, Jeff; Jozwiak, Chris; Smallwood, Chris L.; Eisaki, H.; Kaindl, Robert A.; Lee, Dung-Hai; Lanzara, Alessandra

    2011-06-03

    High-T{sub c} cuprate superconductors are characterized by a strong momentum-dependent anisotropy between the low energy excitations along the Brillouin zone diagonal (nodal direction) and those along the Brillouin zone face (antinodal direction). Most obvious is the d-wave superconducting gap, with the largest magnitude found in the antinodal direction and no gap in the nodal direction. Additionally, while antin- odal quasiparticle excitations appear only below T{sub c}, superconductivity is thought to be indifferent to nodal excitations as they are regarded robust and insensitive to T{sub c}. Here we reveal an unexpected tie between nodal quasiparticles and superconductivity using high resolution time- and angle-resolved photoemission on optimally doped Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+{delta}} . We observe a suppression of the nodal quasiparticle spectral weight following pump laser excitation and measure its recovery dynamics. This suppression is dramatically enhanced in the superconducting state. These results reduce the nodal-antinodal dichotomy and challenge the conventional view of nodal excitation neutrality in superconductivity. The electronic structures of high-Tc cuprates are strongly momentum-dependent. This is one reason why the momentum-resolved technique of angle-resolved photoemission spectroscopy (ARPES) has been a central tool in the field of high-temperature superconductivity. For example, coherent low energy excitations with momenta near the Brillouin zone face, or antinodal quasiparticles (QPs), are only observed below T{sub c} and have been linked to superfluid density. They have therefore been the primary focus of ARPES studies. In contrast, nodal QPs, with momenta along the Brillouin zone diagonal, have received less attention and are usually regarded as largely immune to the superconducting transition because they seem insensitive to perturbations such as disorder, doping, isotope exchange, charge ordering, and temperature. Clearly

  18. ETS transcription factors in embryonic vascular development.

    PubMed

    Craig, Michael P; Sumanas, Saulius

    2016-07-01

    At least thirteen ETS-domain transcription factors are expressed during embryonic hematopoietic or vascular development and potentially function in the formation and maintenance of the embryonic vasculature or blood lineages. This review summarizes our current understanding of the specific roles played by ETS factors in vasculogenesis and angiogenesis and the implications of functional redundancies between them.

  19. Impact of Incidental Irradiation on Clinically Uninvolved Nodal Regions in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Involved-Field Radiation Therapy: Does Incidental Irradiation Contribute to the Low Incidence of Elective Nodal Failure?

    SciTech Connect

    Kimura, Tomoki; Togami, Taro; Nishiyama, Yoshihiro; Ohkawa, Motoomi; Takashima, Hitoshi

    2010-06-01

    Purpose: To evaluate the incidental irradiation dose to elective nodal regions in the treatment of advanced non-small-cell lung cancer with involved-field radiation therapy (IF-RT) and the pattern of elective nodal failure (ENF). Methods and Materials: Fifty patients with advanced non-small-cell lung cancer, who received IF-RT at Kagawa University were enrolled. To evaluate the dose of incidental irradiation, we delineated nodal regions with a Japanese map and the American Thoracic Society map (levels 1-11) in each patient retrospectively and calculated the dose parameters such as mean dose, D95, and V95 (40 Gy as the prescribed dose of elective nodal irradiation). Results: Using the Japanese map, the median mean dose was more than 40 Gy in most of the nodal regions, except at levels 1, 3, and 7. In particular, each dosimetric parameter of level 1 was significantly lower than those at other levels, and each dosimetric parameter of levels 10 to 11 ipsilateral (11I) was significantly higher than those in other nodal regions. Using the American Thoracic Society map, basically, the results were similar to those of the Japanese map. ENF was observed in 4 patients (8%), five nodal regions, and no mean dose to the nodal region exceeded 40 Gy. On the Japanese map, each parameter of these five nodal region was significantly lower than those of the other nodal regions. Conclusions: These results show that a high dose of incidental irradiation may contribute to the low incidence of ENF in patients who have received IF-RT.

  20. Spontaneous embryonic motility: an enduring legacy.

    PubMed

    Bekoff, A

    2001-04-01

    This chapter addresses the influential contributions Viktor Hamburger has made to our understanding of embryonic motor behavior. With his classic review, published in 1963, Viktor Hamburger opened up the field of embryonic motor behavior, which had lain almost completely dormant for many years. He focused his observations and experimental studies on the spontaneously generated embryonic movements rather than on reflex responses. As a result, he and his colleagues firmly established the central generation of embryonic motility as a basic component of embryonic behavior in chicks. These studies were also extended to rat fetuses, showing that similar principles apply to mammalian fetuses. All of us who have followed after him owe Viktor Hamburger an enormous debt of gratitude for his pioneering work. PMID:11255029

  1. Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation.

    PubMed

    Salomonis, Nathan; Schlieve, Christopher R; Pereira, Laura; Wahlquist, Christine; Colas, Alexandre; Zambon, Alexander C; Vranizan, Karen; Spindler, Matthew J; Pico, Alexander R; Cline, Melissa S; Clark, Tyson A; Williams, Alan; Blume, John E; Samal, Eva; Mercola, Mark; Merrill, Bradley J; Conklin, Bruce R

    2010-06-01

    Two major goals of regenerative medicine are to reproducibly transform adult somatic cells into a pluripotent state and to control their differentiation into specific cell fates. Progress toward these goals would be greatly helped by obtaining a complete picture of the RNA isoforms produced by these cells due to alternative splicing (AS) and alternative promoter selection (APS). To investigate the roles of AS and APS, reciprocal exon-exon junctions were interrogated on a genome-wide scale in differentiating mouse embryonic stem (ES) cells with a prototype Affymetrix microarray. Using a recently released open-source software package named AltAnalyze, we identified 144 genes for 170 putative isoform variants, the majority (67%) of which were predicted to alter protein sequence and domain composition. Verified alternative exons were largely associated with pathways of Wnt signaling and cell-cycle control, and most were conserved between mouse and human. To examine the functional impact of AS, we characterized isoforms for two genes. As predicted by AltAnalyze, we found that alternative isoforms of the gene Serca2 were targeted by distinct microRNAs (miRNA-200b, miRNA-214), suggesting a critical role for AS in cardiac development. Analysis of the Wnt transcription factor Tcf3, using selective knockdown of an ES cell-enriched and characterized isoform, revealed several distinct targets for transcriptional repression (Stmn2, Ccnd2, Atf3, Klf4, Nodal, and Jun) as well as distinct differentiation outcomes in ES cells. The findings herein illustrate a critical role for AS in the specification of ES cells with differentiation, and highlight the utility of global functional analyses of AS. PMID:20498046

  2. Multiplicity of positive and nodal solutions for scalar field equations

    NASA Astrophysics Data System (ADS)

    Cerami, Giovanna; Molle, Riccardo; Passaseo, Donato

    2014-11-01

    In this paper the question of finding infinitely many solutions to the problem -Δu+a(x)u=|u, in RN, u∈H1(RN), is considered when N≥2, p∈(2,2N/(N-2)), and the potential a(x) is a positive function which is not required to enjoy symmetry properties. Assuming that a(x) satisfies a suitable “slow decay at infinity” condition and, moreover, that its graph has some “dips”, we prove that the problem admits either infinitely many nodal solutions or infinitely many constant sign solutions. The proof method is purely variational and allows to describe the shape of the solutions. a(x)→a∞>0 as|x|→∞, a(x)≥a0>0 ∀x∈RN, a∈LlocN/2(RN), ∃ηbar∈(0,√{a∞}):lim|x|→∞ ⁡(a(x)-a∞)e=∞ be satisfied.Then there exists a positive constant,A=A(N,ηbar,a0,a∞)∈R, such that, when|a(x)-a∞|N/2,loc:=supy∈RN ⁡|a(x)-a∞|L(B1(y))The above result (see also the subsequent [3] for a different proof and more general nonlinearities) is the starting point of our work; some comments and questions come naturally looking at its statement. Indeed, assumptions (h1)-(h3) are standard and very mild, moreover, the slow decay condition (h4) is basic and it is the deep motivation for the success in obtaining “multibump” solutions. The solutions are found by a max-min argument on the action functional I restricted to special classes of multibump functions

  3. Prevalence and distribution pattern of nodal metastases in advanced ovarian cancer

    PubMed Central

    Bachmann, Cornelia; Bachmann, Robert; Kraemer, Bernhard; Brucker, Sara Yvonne; Staebler, Anette; Fend, Falko; Rothmund, Ralf; Wallwiener, Diethelm

    2016-01-01

    The objective of this study was to examine the relevance of pelvic and para-aortic lymph node involvement and the tumour characteristics affecting nodal metastases and survival in primary advanced ovarian cancer. A total of 130 consecutive patients were retrospectively investigated. All the patients received stage-related surgery with pelvic and para-aortic lymphadenectomy. The median follow-up was 53.5 months. The clinicopathological parameters and distribution pattern of nodal metastases were evaluated. Lymph node metastases were detectable in 74.62% of the cases. Overall, both pelvic and para-aortic nodes were affected in 35.9% of the patients, whereas 13.3% had metastases only in the pelvic and 13.3% only in the para-aortic lymph nodes. Histological grade 1/2 and 3, serous and endometrioid histology were independent predictors of nodal metastasis. Serous and endometrioid cancers have shown a predilection for metastasis to the pelvic lymph nodes alone, both to the pelvic and the para-aortic nodes, or the para-aortic nodes alone. Overall survival was significantly positively affected by serous histology with positive nodes (P=0.043). It is crucial to investigate the risk factors and metastatic patterns of such patients in a multicenter analysis to evaluate individual subgroups. Prospective studies are required to investigate the prognostic effect of lymphadenectomy in advanced ovarian cancer and its association with histology and distribution pattern of nodal metastasis. PMID:27703680

  4. Precision evaluation of lens systems using a nodal slide/MTF optical bench

    NASA Astrophysics Data System (ADS)

    Doherty, Victor J.; Chapnik, Philip D.

    1992-01-01

    A compact, self-contained production instrument designed to permit the rapid and precise performance characterization of a wide variety of lenses and optical systems has been developed by Eidolon Corporation. The Eidolon Production Nodal Slide/MTF Measurement System can be used to measure effective focal length (EFL), distortion, field curvature, chromatic aberration, spot size, and modulation transfer function (MTF).

  5. Photoacoustic intra-operative nodal staging using clinically approved superparamagnetic iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Grootendorst, Diederik J.; Fratila, Raluca M.; Visscher, Martijn; Ten Haken, Bennie; van Wezel, Richard; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J. M.

    2013-02-01

    Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value of superparamagnetic iron oxide dispersions (SPIOs) for nodal staging purposes, prompting the clearance of different SPIO dispersions for clinical practice. We evaluate whether a combination of photoacoustic (PA) imaging and a clinically approved SPIO dispersion, could be applied for intra-operative nodal staging. Metastatic adenocarcinoma was inoculated in Copenhagen rats for 5 or 8 days. After SPIO injection, the lymph nodes were photoacoustically imaged both in vivo and ex vivo whereafter imaging results were correlated with MR and histology. Results were compared to a control group without tumor inoculation. In the tumor groups clear irregularities, as small as 1 mm, were observed in the PA contrast pattern of the nodes together with an decrease of PA response. These irregularities could be correlated to the absence of contrast in the MR images and could be linked to metastatic deposits seen in the histological slides. The PA and MR images of the control animals did not show these features. We conclude that the combination of photoacoustic imaging with a clinically approved iron oxide nanoparticle dispersion is able to detect lymph node metastases in an animal model. This approach opens up new possibilities for fast intra-operative nodal staging in a clinical setting.

  6. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... authorized only as a part of an integrated communication system wherein 10.6 GHz DEMS User Stations... 47 Telecommunication 5 2013-10-01 2013-10-01 false Digital Electronic Message Service Nodal Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED)...

  7. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... authorized only as a part of an integrated communication system wherein 10.6 GHz DEMS User Stations... 47 Telecommunication 5 2012-10-01 2012-10-01 false Digital Electronic Message Service Nodal Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED)...

  8. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... authorized only as a part of an integrated communication system wherein 10.6 GHz DEMS User Stations... 47 Telecommunication 5 2014-10-01 2014-10-01 false Digital Electronic Message Service Nodal Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED)...

  9. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... authorized only as a part of an integrated communication system wherein 10.6 GHz DEMS User Stations... 47 Telecommunication 5 2011-10-01 2011-10-01 false Digital Electronic Message Service Nodal Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED)...

  10. NOKIN1D: one-dimensional neutron kinetics based on a nodal collocation method

    NASA Astrophysics Data System (ADS)

    Verdú, G.; Ginestar, D.; Miró, R.; Jambrina, A.; Barrachina, T.; Soler, Amparo; Concejal, Alberto

    2014-06-01

    The TRAC-BF1 one-dimensional kinetic model is a formulation of the neutron diffusion equation in the two energy groups' approximation, based on the analytical nodal method (ANM). The advantage compared with a zero-dimensional kinetic model is that the axial power profile may vary with time due to thermal-hydraulic parameter changes and/or actions of the control systems but at has the disadvantages that in unusual situations it fails to converge. The nodal collocation method developed for the neutron diffusion equation and applied to the kinetics resolution of TRAC-BF1 thermal-hydraulics, is an adaptation of the traditional collocation methods for the discretization of partial differential equations, based on the development of the solution as a linear combination of analytical functions. It has chosen to use a nodal collocation method based on a development of Legendre polynomials of neutron fluxes in each cell. The qualification is carried out by the analysis of the turbine trip transient from the NEA benchmark in Peach Bottom NPP using both the original 1D kinetics implemented in TRAC-BF1 and the 1D nodal collocation method.

  11. Three-Dimensional, Nodal, Neutron Diffusion Criticality Code System in Hex-Z Geometry.

    1992-07-27

    Version: 00 SIXTUS-3 is a 3D extention of SIXTUS-2 and is based on a response matrix nodal model. The code offers a fast and accurate analysis of critical systems in the regular hex-z geometry with the multigroup cross section representation including arbitrary upscattering.

  12. A nodal spectral stiffness matrix for the finite-element method

    NASA Astrophysics Data System (ADS)

    Bittencourt, Marco L.; Vazquez, Thais G.

    2008-12-01

    In this paper, shape functions are proposed for the spectral finite-element method aiming to finding a nodal spectral stiffness matrix. The proposed shape functions obtain a nearly diagonal 1D stiffness matrix with better conditioning than using the Lagrange and Jacobi bases.

  13. Nodal Analysis Optimization Based on the Use of Virtual Current Sources: A Powerful New Pedagogical Method

    ERIC Educational Resources Information Center

    Chatzarakis, G. E.

    2009-01-01

    This paper presents a new pedagogical method for nodal analysis optimization based on the use of virtual current sources, applicable to any linear electric circuit (LEC), regardless of its complexity. The proposed method leads to straightforward solutions, mostly arrived at by inspection. Furthermore, the method is easily adapted to computer…

  14. Analysis of nodal aberration properties in off-axis freeform system design.

    PubMed

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design. PMID:27557003

  15. Nodal Green’s Function Method Singular Source Term and Burnable Poison Treatment in Hexagonal Geometry

    SciTech Connect

    A.A. Bingham; R.M. Ferrer; A.M. ougouag

    2009-09-01

    An accurate and computationally efficient two or three-dimensional neutron diffusion model will be necessary for the development, safety parameters computation, and fuel cycle analysis of a prismatic Very High Temperature Reactor (VHTR) design under Next Generation Nuclear Plant Project (NGNP). For this purpose, an analytical nodal Green’s function solution for the transverse integrated neutron diffusion equation is developed in two and three-dimensional hexagonal geometry. This scheme is incorporated into HEXPEDITE, a code first developed by Fitzpatrick and Ougouag. HEXPEDITE neglects non-physical discontinuity terms that arise in the transverse leakage due to the transverse integration procedure application to hexagonal geometry and cannot account for the effects of burnable poisons across nodal boundaries. The test code being developed for this document accounts for these terms by maintaining an inventory of neutrons by using the nodal balance equation as a constraint of the neutron flux equation. The method developed in this report is intended to restore neutron conservation and increase the accuracy of the code by adding these terms to the transverse integrated flux solution and applying the nodal Green’s function solution to the resulting equation to derive a semi-analytical solution.

  16. Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1

    PubMed Central

    Housley, Michael P.; Weiner, Orion D.

    2012-01-01

    Embryo morphogenesis is driven by dynamic cell behaviors, including migration, that are coordinated with fate specification and differentiation, but how such coordination is achieved remains poorly understood. During zebrafish gastrulation, endodermal cells sequentially exhibit first random, nonpersistent migration followed by oriented, persistent migration and finally collective migration. Using a novel transgenic line that labels the endodermal actin cytoskeleton, we found that these stage-dependent changes in migratory behavior correlated with changes in actin dynamics. The dynamic actin and random motility exhibited during early gastrulation were dependent on both Nodal and Rac1 signaling. We further identified the Rac-specific guanine nucleotide exchange factor Prex1 as a Nodal target and showed that it mediated Nodal-dependent random motility. Reducing Rac1 activity in endodermal cells caused them to bypass the random migration phase and aberrantly contribute to mesodermal tissues. Together, our results reveal a novel role for Nodal signaling in regulating actin dynamics and migration behavior, which are crucial for endodermal morphogenesis and cell fate decisions. PMID:22945937

  17. Analysis of nodal aberration properties in off-axis freeform system design.

    PubMed

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design.

  18. Sensitivity derivatives and optimization of nodal point locations for vibration reduction

    NASA Technical Reports Server (NTRS)

    Pritchard, Jocelyn I.; Adelman, Howard M.; Haftka, Raphael T.

    1987-01-01

    A method is developed for sensitivity analysis and optimization of nodal point locations in connection with vibration reduction. A straightforward derivation of the expression for the derivative of nodal locations is given, and the role of the derivative in assessing design trends is demonstrated. An optimization process is developed which uses added lumped masses on the structure as design variables to move the node to a preselected location; for example, where low response amplitude is required or to a point which makes the mode shape nearly orthogonal to the force distribution, thereby minimizing the generalized force. The optimization formulation leads to values for added masses that adjust a nodal location while minimizing the total amount of added mass required to do so. As an example, the node of the second mode of a cantilever box beam is relocated to coincide with the centroid of a prescribed force distribution, thereby reducing the generalized force substantially without adding excessive mass. A comparison with an optimization formulation that directly minimizes the generalized force indicates that nodal placement gives essentially a minimum generalized force when the node is appropriately placed.

  19. Senstitivty analysis and optimization of nodal point placement for vibration reduction

    NASA Technical Reports Server (NTRS)

    Pritchard, J. I.; Adelman, H. M.; Haftka, R. T.

    1986-01-01

    A method is developed for sensitivity analysis and optimization of nodal point locations in connection with vibration reduction. A straightforward derivation of the expression for the derivative of nodal locations is given, and the role of the derivative in assessing design trends is demonstrated. An optimization process is developed which uses added lumped masses on the structure as design variables to move the node to a preselected location - for example, where low response amplitude is required or to a point which makes the mode shape nearly orthogonal to the force distribution, thereby minimizing the generalized force. The optimization formulation leads to values for added masses that adjust a nodal location while minimizing the total amount of added mass required to do so. As an example, the node of the second mode of a cantilever box beam is relocated to coincide with the centroid of a prescribed force distribution, thereby reducing the generalized force substantially without adding excessive mass. A comparison with an optimization formulation that directly minimizes the generalized force indicates that nodal placement gives essentially a minimum generalized force when the node is appropriately placed.

  20. A difference-equation formalism for the nodal domains of separable billiards

    NASA Astrophysics Data System (ADS)

    Manjunath, Naren; Samajdar, Rhine; Jain, Sudhir R.

    2016-09-01

    Recently, the nodal domain counts of planar, integrable billiards with Dirichlet boundary conditions were shown to satisfy certain difference equations in Samajdar and Jain (2014). The exact solutions of these equations give the number of domains explicitly. For complete generality, we demonstrate this novel formulation for three additional separable systems and thus extend the statement to all integrable billiards.

  1. Radiation therapy for carcinoma of the hypopharynx with special reference to nodal control

    SciTech Connect

    Teshima, T.; Chatani, M.; Inoue, T.; Miyahara, H.; Sato, T.

    1988-05-01

    From October 1977 through December 1983, 61 patients with carcinoma of the hypopharynx were treated with radiation therapy (RT) and surgery or with RT alone. Five-year survival rates by N-stage, according to the TNM classification by UICC (1978), were 52% for N0 cases, 23% for N1, and 17% for N2-3 (N1 vs. N2-3, not significant). For N1-3 cases, corresponding figures by level of cervical nodal involvement by UICC (1978) were 29% for level 3 cases, 15% for level 2, and 8% for level 4 (level 3 vs. level 4, p less than 0.04). Therefore, the level of cervical nodal involvement was a more useful prognosticator for patients with nodal metastasis than the N-stage. Effective nodal control for patients with clinically positive nodes (N1-3) was obtained with a combination of neck node dissection and RT of 50 Gy or more. For N0 cases, elective RT of 50 Gy or more, encompassing an adequate field, was required.

  2. Topological nodal-line semimetals in alkaline-earth stannides, germanides, and silicides

    NASA Astrophysics Data System (ADS)

    Huang, Huaqing; Liu, Jianpeng; Vanderbilt, David; Duan, Wenhui

    2016-05-01

    Based on first-principles calculations and an effective Hamiltonian analysis, we systematically investigate the electronic and topological properties of alkaline-earth compounds A X2 (A =Ca , Sr, Ba; X =Si , Ge, Sn). Taking BaSn2 as an example, we find that when spin-orbit coupling is ignored, these materials are three-dimensional topological nodal-line semimetals characterized by a snakelike nodal loop in three-dimensional momentum space. Drumheadlike surface states emerge either inside or outside the loop circle on the (001) surface depending on surface termination, while complicated double-drumhead-like surface states appear on the (010) surface. When spin-orbit coupling is included, the nodal line is gapped and the system becomes a topological insulator with Z2 topological invariants (1;001). Since spin-orbit coupling effects are weak in light elements, the nodal-line semimetal phase is expected to be achievable in some alkaline-earth germanides and silicides.

  3. Infrared inhibition of embryonic hearts

    NASA Astrophysics Data System (ADS)

    Wang, Yves T.; Rollins, Andrew M.; Jenkins, Michael W.

    2016-06-01

    Infrared control is a new technique that uses pulsed infrared lasers to thermally alter electrical activity. Originally developed for nerves, we have applied this technology to embryonic hearts using a quail model, previously demonstrating infrared stimulation and, here, infrared inhibition. Infrared inhibition enables repeatable and reversible block, stopping cardiac contractions for several seconds. Normal beating resumes after the laser is turned off. The block can be spatially specific, affecting propagation on the ventricle or initiation on the atrium. Optical mapping showed that the block affects action potentials and not just calcium or contraction. Increased resting intracellular calcium was observed after a 30-s exposure to the inhibition laser, which likely resulted in reduced mechanical function. Further optimization of the laser illumination should reduce potential damage. Stopping cardiac contractions by disrupting electrical activity with infrared inhibition has the potential to be a powerful tool for studying the developing heart.

  4. Mammographic Density and Prediction of Nodal Status in Breast Cancer Patients.

    PubMed

    Hack, C C; Häberle, L; Geisler, K; Schulz-Wendtland, R; Hartmann, A; Fasching, P A; Uder, M; Wachter, D L; Jud, S M; Loehberg, C R; Lux, M P; Rauh, C; Beckmann, M W; Heusinger, K

    2013-02-01

    Aim: Nodal status remains one of the most important prognostic factors in breast cancer. The cellular and molecular reasons for the spread of tumor cells to the lymph nodes are not well understood and there are only few predictors in addition to tumor size and multifocality that give an insight into additional mechanisms of lymphatic spread. Aim of our study was therefore to investigate whether breast characteristics such as mammographic density (MD) add to the predictive value of the presence of lymph node metastases in patients with primary breast cancer. Methods: In this retrospective study we analyzed primary, metastasis-free breast cancer patients from one breast center for whom data on MD and staging information were available. A total of 1831 patients were included into this study. MD was assessed as percentage MD (PMD) using a semiautomated method and two readers for every patient. Multiple logistic regression analyses with nodal status as outcome were used to investigate the predictive value of PMD in addition to age, tumor size, Ki-67, estrogen receptor (ER), progesterone receptor (PR), grading, histology, and multi-focality. Results: Multifocality, tumor size, Ki-67 and grading were relevant predictors for nodal status. Adding PMD to a prediction model which included these factors did not significantly improve the prediction of nodal status (p = 0.24, likelihood ratio test). Conclusion: Nodal status could be predicted quite well with the factors multifocality, tumor size, Ki-67 and grading. PMD does not seem to play a role in the lymphatic spread of tumor cells. It could be concluded that the amount of extracellular matrix and stromal cell content of the breast which is reflected by MD does not influence the probability of malignant breast cells spreading from the primary tumor to the lymph nodes.

  5. Concordance of studies for nodal staging is prognostic for worse survival in esophageal cancer.

    PubMed

    Dhupar, R; Correa, A M; Ajani, J; Betancourt, S; Mehran, R J; Swisher, S G; Hofstetter, W L

    2014-01-01

    Pretreatment clinical staging in esophageal cancer influences prognosis and treatment strategy. Current staging strategies utilize multiple imaging modalities, and often the results are contradictory. No studies have examined the implications of concordance of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) when used for the evaluation of nodal disease. The objective of this study was to determine if concordance of CT, PET, or EUS for nodal disease predicts worse overall survival. We reviewed 615 esophageal cancer patients with pretreatment CT, PET, and EUS that underwent esophagectomy for survival outcomes based on concordance of studies for nodal disease. Concordant N+ is defined as two or three studies positive for nodal disease; non-concordant N+ is defined as only one positive study. Node-positive disease by any study predicted shorter survival than node-negative disease (42% vs. 73% 5-year survival; P<0.001). Additionally, non-concordant N+ patients had shorter survival than N- patients (52% vs. 73% 5-year survival; P<0.001). Concordant N+ patients had shorter survival than non-concordant N+ patients (38- vs. 61-month median survival; P=0.017). There were no statistically significant differences in survival based on specific combinations of studies. When PET was disregarded, patients with both CT+ and EUS+ had shorter survival than patients with either CT+ or EUS+ (39- vs. 58-month median survival; P=0.029). Pretreatment CT, PET, or EUS concordance for node-positive disease predicts shorter overall survival in patients that undergo esophagectomy for esophageal cancer. Predicting survival in esophageal cancer should consider the synergistic capabilities of CT, PET, and EUS in evaluating nodal status.

  6. An approach to model reactor core nodalization for deterministic safety analysis

    NASA Astrophysics Data System (ADS)

    Salim, Mohd Faiz; Samsudin, Mohd Rafie; Mamat @ Ibrahim, Mohd Rizal; Roslan, Ridha; Sadri, Abd Aziz; Farid, Mohd Fairus Abd

    2016-01-01

    Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to be employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH1.6, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D® computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.

  7. Radiotherapy for Esthesioneuroblastoma: Is Elective Nodal Irradiation Warranted in the Multimodality Treatment Approach?

    SciTech Connect

    Noh, O Kyu; Lee, Sang-wook; Yoon, Sang Min; Kim, Sung Bae; Kim, Sang Yoon; Kim, Chang Jin; Jo, Kyung Ja; Choi, Eun Kyung; Song, Si Yeol; Kim, Jong Hoon; Ahn, Seung Do

    2011-02-01

    Purpose: The role of elective nodal irradiation (ENI) in radiotherapy for esthesioneuroblastoma (ENB) has not been clearly defined. We analyzed treatment outcomes of patients with ENB and the frequency of cervical nodal failure in the absence of ENI. Methods and Materials: Between August 1996 and December 2007, we consulted with 19 patients with ENB regarding radiotherapy. Initial treatment consisted of surgery alone in 2 patients; surgery and postoperative radiotherapy in 4; surgery and adjuvant chemotherapy in 1; surgery, postoperative radiotherapy, and chemotherapy in 3; and chemotherapy followed by radiotherapy or concurrent chemoradiotherapy in 5. Five patients did not receive planned radiotherapy because of disease progression. Including 2 patients who received salvage radiotherapy, 14 patients were treated with radiotherapy. Elective nodal irradiation was performed in 4 patients with high-risk factors, including 3 with cervical lymph node metastasis at presentation. Results: Fourteen patients were analyzable, with a median follow-up of 27 months (range, 7-64 months). The overall 3-year survival rate was 73.4%. Local failure occurred in 3 patients (21.4%), regional cervical failure in 3 (21.4%), and distant failure in 2 (14.3%). No cervical nodal failure occurred in patients treated with combined systemic chemotherapy regardless of ENI. Three cervical failures occurred in the 4 patients treated with ENI or neck dissection (75%), none of whom received systemic chemotherapy. Conclusions: ENI during radiotherapy for ENB seems to play a limited role in preventing cervical nodal failure. Omitting ENI may be an option if patients are treated with a combination of radiotherapy and chemotherapy.

  8. Laser catheter-induced atrioventricular nodal delays and atrioventricular block in dogs: acute and chronic observations.

    PubMed

    Narula, O S; Boveja, B K; Cohen, D M; Narula, J T; Tarjan, P P

    1985-02-01

    Selective modification of atrioventricular (AV) nodal conduction, that is, induction of varying degrees of AV nodal delays or block (second or third degree), or both, was achieved with a pervenous laser catheter technique. In six adult mongrel dogs anesthetized with pentobarbital (Nembutal), 5F leads were placed through femoral and external jugular veins and placed into the right atrium and His bundle region. Through another femoral vein, a 200 micron optical fiber was inserted by way of a 7F catheter with a preformed curved tip. Guided by fluoroscopy and His bundle electrograms, the fiber's tip was positioned in the AV nodal region. After autonomic blockade was achieved with intravenous propranolol (5 mg) and atropine (1 mg), AV conduction was analyzed. An argon laser delivered 3 to 4 watts into the fiber in bursts of 10 seconds' duration until the desired degree of AV nodal delay or block (second or third degree) was manifested. Monitoring of His bundle electrograms was continued for 2 hours. Four weekly serial electrocardiograms were recorded, after which electrophysiologic studies were repeated. Acute post-lasing studies showed that: in all six dogs, the mean PR interval was prolonged from 116 ms (range 100 to 135) to 153 ms (range 120 to 185), with the prolongation being caused exclusively by AH lengthening from 68 ms (range 50 to 90) to 105 ms (range 65 to 140); the mean effective refractory period of the AV node increased from less than 185 ms (range less than 150 to less than 200) to 215 ms (range 190 to 280); and the mean atrial pacing cycle length, at which second degree AV nodal block was manifested, increased from 210 ms (range 160 to 260) to 261 ms (range 205 to 320).(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

    PubMed Central

    Kluth, L A; Abdollah, F; Xylinas, E; Rieken, M; Fajkovic, H; Seitz, C; Sun, M; Karakiewicz, P I; Schramek, P; Herman, M P; Becker, A; Hansen, J; Ehdaie, B; Loidl, W; Pummer, K; Lee, R K; Lotan, Y; Scherr, D S; Seiler, D; Ahyai, S A; Chun, F K-H; Graefen, M; Tewari, A; Nonis, A; Bachmann, A; Montorsi, F; Gönen, M; Briganti, A; Shariat, S F

    2014-01-01

    Background: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. Methods: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. Results: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. Conclusions: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis. PMID:25003663

  10. Regulation of expression driven by human immunodeficiency virus type 1 and human T-cell leukemia virus type I long terminal repeats in pluripotential human embryonic cells

    SciTech Connect

    Maio, J.; Brown, F.L. )

    1988-04-01

    Human pluripotential embryonic teratocarcinoma cells differentially expressed gene activity controlled by the human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) long terminal repeats (LTRs) when differentiation was induced by the morphogen all-trans retinoic acid. The alterations occurred after commitment and before the appearance of the multiple cell types characteristic of these pluripotential cells. After commitment, gene activity controlled by the HIV-1 LTR markedly increased, whereas that controlled by the HTLV-I LTR decreased. Steady-state mRNA levels and nuclear run-on transcription indicated that the increased HIV-1-directed activity during differentiation occurred posttranscriptionally, whereas the decreased HTLV-I activity was at the transcriptional level. Phorbol esters did not cause commitment but strongly enhanced expression by both viral LTRs at the transcriptional level. Differentiating cells gradually lost the ability to respond to phorbol ester stimulation. Experiments with a deletion mutant of the HIV-1 LTR suggested that this was due to imposition of negative regulation during differentiation that was not reversed by phorbol ester induction. Cycloheximide, with or without phorbol ester, slightly stimulated HIV-1-directed activity at the transcriptional level and massively increased the amounts of steady-state mRNA by posttranscriptional superinduction. It appeared, however, that new nuclear protein synthesis was required for maximal transcriptional stimulation by phorbol esters. Thus, changing cellular regulatory mechanisms influenced human retrovirus expression during human embryonic cell differentiation.

  11. [Expression of TGFbeta family factors and FGF2 in mouse and human embryonic stem cells maintained in different culture systems].

    PubMed

    Lifantseva, N V; Kol'tsova, A M; Polianskaia, G G; Gordeeva, O F

    2013-01-01

    Mouse and human embryonic stem cells are in different states of pluripotency (naive/ground and primed states). Mechanisms of signaling regulation in cells with ground and primed states of pluripotency are considerably different. In order to understand the contribution of endogenous and exogenous factors in the maintenance of a metastable state of the cells in different phases ofpluripotency, we examined the expression of TGFbeta family factors (ActivinA, Nodal, Leftyl, TGFbeta1, GDF3, BMP4) and FGF2 initiating the appropriate signaling pathways in mouse and human embryonic stem cells (mESCs, hESCs) and supporting feeder cells. Quantitative real-time PCR analysis of gene expression showed that the expression patterns of endogenous factors studied were considerably different in mESCs and hESCs. The most significant differences were found in the levels of endogenous expression of TGFbeta1, BMP4 and ActivinA. The sources of exogenous factors ActivnA, TGFbeta1, and FGF2 for hESCs are feeder cells (mouse and human embryonic fibroblasts) expressing high levels of these factors, as well as low levels of BMP4. Thus, our data demonstrated that the in vitro maintenance of metastable state of undifferentiated pluripotent cells is achieved in mESCs and hESCs using different schemes of the regulations of ActivinA/Nodal/Lefty/Smad2/3BMP/Smad1/5/8 endogenous branches of TGFbeta signaling. The requirement for exogenous stimulation or inhibition of these signaling pathways is due to different patterns of endogenous expression of TGFbeta family factors and FGF2 in the mESCs and hESCs. For the hESCs, enhanced activity of ActivinA/Nodal/Lefty/Smad2/3 signaling by exogenous factor stimulation is necessary to mitigate the effects of BMP/Smadl/5/8 signaling pathways that promote cell differentiation into the extraembryonic structures. Significant differences in endogenous FGF2 expression in the cells in the ground and primary states of pluripotency demonstrate diverse involvement of this

  12. Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation.

    PubMed

    Halder, Debasish; Park, Ji Hyun; Choi, Mi Ran; Chai, Jin Choul; Lee, Young Seek; Mandal, Chanchal; Jung, Kyoung Hwa; Chai, Young Gyu

    2014-01-01

    Fetal alcohol spectrum disorder (FASD) is a set of developmental malformations caused by excess alcohol consumption during pregnancy. Using an in vitro system, we examined the role that chronic ethanol (EtOH) exposure plays in gene expression changes during the early stage of embryonic differentiation. We demonstrated that EtOH affected the cell morphology, cell cycle progression and also delayed the down-regulation of OCT4 and NANOG during differentiation. Gene expression profiling and pathway analysis demonstrated that EtOH deregulates many genes and pathways that are involved in early embryogenesis. Follow-up analyzes revealed that EtOH exposure to embryoid bodies (EBs) induced the expression of an organizer-specific gene, goosecoid (GSC), in comparison to controls. Moreover, EtOH treatment altered several important genes that are involved in embryonic structure formation, nervous system development, and placental and embryonic vascularization, which are all common processes that FASD can disrupt. Specifically, EtOH treatment let to a reduction in ALDOC, ENO2 and CDH1 expression, whereas EtOH treatment induced the expression of PTCH1, EGLN1, VEGFA and DEC2 in treated EBs. We also found that folic acid (FA) treatment was able to correct the expression of the majority of genes deregulated by EtOH exposure during early embryo development. Finally, the present study identified a gene set including GSC, which was deregulated by EtOH exposure that may contribute to the etiology of fetal alcohol syndrome (FAS). We also reported that EtOH-induced GSC expression is mediated by Nodal signaling, which may provide a new avenue for analyzing the molecular mechanisms behind EtOH teratogenicity in FASD individuals.

  13. Role of microglia in embryonic neurogenesis

    PubMed Central

    Tong, Chih Kong

    2016-01-01

    Microglia begin colonizing the developing brain as early as embryonic day 9, prior to the emergence of neurons and other glia. Their ontogeny is also distinct from other central nervous system cells, as they derive from yolk sac hematopoietic progenitors and not neural progenitors. In this review, we feature these unique characteristics of microglia and assess the spatiotemporal similarities between microglia colonization of the central nervous system and embryonic neurogenesis. We also infer to existing evidence for microglia function from embryonic through to postnatal neurodevelopment to postulate roles for microglia in neurogenesis. PMID:27555616

  14. Role of microglia in embryonic neurogenesis.

    PubMed

    Tong, Chih Kong; Vidyadaran, Sharmili

    2016-09-01

    Microglia begin colonizing the developing brain as early as embryonic day 9, prior to the emergence of neurons and other glia. Their ontogeny is also distinct from other central nervous system cells, as they derive from yolk sac hematopoietic progenitors and not neural progenitors. In this review, we feature these unique characteristics of microglia and assess the spatiotemporal similarities between microglia colonization of the central nervous system and embryonic neurogenesis. We also infer to existing evidence for microglia function from embryonic through to postnatal neurodevelopment to postulate roles for microglia in neurogenesis. PMID:27555616

  15. Dual Inhibition of Activin/Nodal/TGF-β and BMP Signaling Pathways by SB431542 and Dorsomorphin Induces Neuronal Differentiation of Human Adipose Derived Stem Cells

    PubMed Central

    Madhu, Vedavathi; Dighe, Abhijit S.; Cui, Quanjun; Deal, D. Nicole

    2016-01-01

    Damage to the nervous system can cause devastating diseases or musculoskeletal dysfunctions and transplantation of progenitor stem cells can be an excellent treatment option in this regard. Preclinical studies demonstrate that untreated stem cells, unlike stem cells activated to differentiate into neuronal lineage, do not survive in the neuronal tissues. Conventional methods of inducing neuronal differentiation of stem cells are complex and expensive. We therefore sought to determine if a simple, one-step, and cost effective method, previously reported to induce neuronal differentiation of embryonic stem cells and induced-pluripotent stem cells, can be applied to adult stem cells. Indeed, dual inhibition of activin/nodal/TGF-β and BMP pathways using SB431542 and dorsomorphin, respectively, induced neuronal differentiation of human adipose derived stem cells (hADSCs) as evidenced by formation of neurite extensions, protein expression of neuron-specific gamma enolase, and mRNA expression of neuron-specific transcription factors Sox1 and Pax6 and matured neuronal marker NF200. This process correlated with enhanced phosphorylation of p38, Erk1/2, PI3K, and Akt1/3. Additionally, in vitro subcutaneous implants of SB431542 and dorsomorphin treated hADSCs displayed significantly higher expression of active-axonal-growth-specific marker GAP43. Our data offers novel insights into cell-based therapies for the nervous system repair. PMID:26798350

  16. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava.

    PubMed

    Röttinger, Eric; DuBuc, Timothy Q; Amiel, Aldine R; Martindale, Mark Q

    2015-01-01

    Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms. PMID:25979707

  17. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava.

    PubMed

    Röttinger, Eric; DuBuc, Timothy Q; Amiel, Aldine R; Martindale, Mark Q

    2015-05-15

    Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms.

  18. Nodal signaling is required for mesodermal and ventral but not for dorsal fates in the indirect developing hemichordate, Ptychodera flava

    PubMed Central

    Röttinger, Eric; DuBuc, Timothy Q.; Amiel, Aldine R.; Martindale, Mark Q.

    2015-01-01

    ABSTRACT Nodal signaling plays crucial roles in vertebrate developmental processes such as endoderm and mesoderm formation, and axial patterning events along the anteroposterior, dorsoventral and left-right axes. In echinoderms, Nodal plays an essential role in the establishment of the dorsoventral axis and left-right asymmetry, but not in endoderm or mesoderm induction. In protostomes, Nodal signaling appears to be involved only in establishing left-right asymmetry. Hence, it is hypothesized that Nodal signaling has been co-opted to pattern the dorsoventral axis of deuterostomes and for endoderm, mesoderm formation as well as anteroposterior patterning in chordates. Hemichordata, together with echinoderms, represent the sister taxon to chordates. In this study, we analyze the role of Nodal signaling in the indirect developing hemichordate Ptychodera flava. In particular, we show that during gastrulation nodal transcripts are detected in a ring of cells at the vegetal pole that gives rise to endomesoderm and in the ventral ectoderm at later stages of development. Inhibition of Nodal function disrupts dorsoventral fates and also blocks formation of the larval mesoderm. Interestingly, molecular analysis reveals that only mesodermal, apical and ventral gene expression is affected while the dorsal side appears to be patterned correctly. Taken together, this study suggests that the co-option of Nodal signaling in mesoderm formation and potentially in anteroposterior patterning has occurred prior to the emergence of chordates and that Nodal signaling on the ventral side is uncoupled from BMP signaling on the dorsal side, representing a major difference from the molecular mechanisms of dorsoventral patterning events in echinoderms. PMID:25979707

  19. Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture.

    PubMed

    Schulz, Thomas C; Noggle, Scott A; Palmarini, Gail M; Weiler, Deb A; Lyons, Ian G; Pensa, Kate A; Meedeniya, Adrian C B; Davidson, Bruce P; Lambert, Nevin A; Condie, Brian G

    2004-01-01

    The use of human embryonic stem cells (hESCs) as a source of dopaminergic neurons for Parkinson's disease cell therapy will require the development of simple and reliable cell differentiation protocols. The use of cell cocultures, added extracellular signaling factors, or transgenic approaches to drive hESC differentiation could lead to additional regulatory as well as cell production delays for these therapies. Because the neuronal cell lineage seems to require limited or no signaling for its formation, we tested the ability of hESCs to differentiate to form dopamine-producing neurons in a simple serum-free suspension culture system. BG01 and BG03 hESCs were differentiated as suspension aggregates, and neural progenitors and neurons were detectable after 2-4 weeks. Plated neurons responded appropriately to electrophysiological cues. This differentiation was inhibited by early exposure to bone morphogenic protein (BMP)-4, but a pulse of BMP-4 from days 5 to 9 caused induction of peripheral neuronal differentiation. Real-time polymerase chain reaction and whole-mount immunocytochemistry demonstrated the expression of multiple markers of the midbrain dopaminergic phenotype in serum-free differentiations. Neurons expressing tyrosine hydroxylase (TH) were killed by 6-hydroxydopamine (6-OHDA), a neurotoxic catecholamine. Upon plating, these cells released dopamine and other catecholamines in response to K+ depolarization. Surviving TH+ neurons, derived from the cells differentiated in serum-free suspension cultures, were detected 8 weeks after transplantation into 6-OHDA-lesioned rat brains. This work suggests that hESCs can differentiate in simple serum-free suspension cultures to produce the large number of cells required for transplantation studies. PMID:15579641

  20. Coordination of Cell Differentiation and Migration in Mathematical Models of Caudal Embryonic Axis Extension

    PubMed Central

    Harrison, Nigel C.; Diez del Corral, Ruth; Vasiev, Bakhtier

    2011-01-01

    Vertebrate embryos display a predominant head-to-tail body axis whose formation is associated with the progressive development of post-cranial structures from a pool of caudal undifferentiated cells. This involves the maintenance of active FGF signaling in this caudal region as a consequence of the restricted production of the secreted factor FGF8. FGF8 is transcribed specifically in the caudal precursor region and is down-regulated as cells differentiate and the embryo extends caudally. We are interested in understanding the progressive down-regulation of FGF8 and its coordination with the caudal movement of cells which is also known to be FGF-signaling dependent. Our study is performed using mathematical modeling and computer simulations. We use an individual-based hybrid model as well as a caricature continuous model for the simulation of experimental observations (ours and those known from the literature) in order to examine possible mechanisms that drive differentiation and cell movement during the axis elongation. Using these models we have identified a possible gene regulatory network involving self-repression of a caudal morphogen coupled to directional domain movement that may account for progressive down-regulation of FGF8 and conservation of the FGF8 domain of expression. Furthermore, we have shown that chemotaxis driven by molecules, such as FGF8 secreted in the stem zone, could underlie the migration of the caudal precursor zone and, therefore, embryonic axis extension. These mechanisms may also be at play in other developmental processes displaying a similar mode of axis extension coupled to cell differentiation. PMID:21829483

  1. Interaction between SCO-spondin and low density lipoproteins from embryonic cerebrospinal fluid modulates their roles in early neurogenesis

    PubMed Central

    Vera, América; Recabal, Antonia; Saldivia, Natalia; Stanic, Karen; Torrejón, Marcela; Montecinos, Hernán; Caprile, Teresa

    2015-01-01

    During early stages of development, encephalic vesicles are composed by a layer of neuroepithelial cells surrounding a central cavity filled with embryonic cerebrospinal fluid (eCSF). This fluid contains several morphogens that regulate proliferation and differentiation of neuroepithelial cells. One of these neurogenic factors is SCO-spondin, a giant protein secreted to the eCSF from early stages of development. Inhibition of this protein in vivo or in vitro drastically decreases the neurodifferentiation process. Other important neurogenic factors of the eCSF are low density lipoproteins (LDL), the depletion of which generates a 60% decrease in mesencephalic explant neurodifferentiation. The presence of several LDL receptor class A (LDLrA) domains (responsible for LDL binding in other proteins) in the SCO-spondin sequence suggests a possible interaction between both molecules. This possibility was analyzed using three different experimental approaches: (1) Bioinformatics analyses of the SCO-spondin region, that contains eight LDLrA domains in tandem, and of comparisons with the LDL receptor consensus sequence; (2) Analysis of the physical interactions of both molecules through immunohistochemical colocalization in embryonic chick brains and through the immunoprecipitation of LDL with anti-SCO-spondin antibodies; and (3) Analysis of functional interactions during the neurodifferentiation process when these molecules were added to a culture medium of mesencephalic explants. The results revealed that LDL and SCO-spondin interact to form a complex that diminishes the neurogenic capacities that both molecules have separately. Our work suggests that the eCSF is an active signaling center with a complex regulation system that allows for correct brain development. PMID:26074785

  2. Embryonal rhabdomyosarcoma: A rare oral tumor

    PubMed Central

    Datta, Sila; Ray, Jay Gopal; Deb, Tushar; Patsa, Santanu

    2016-01-01

    Rhabdomyosarcoma is the malignant neoplasm of striated muscle and a relatively uncommon tumor of the oral cavity. Embryonal variety is the most common subtype, observed in children below 10 years of age but occasionally seen in adolescents and young adults. The present report describes a case of embryonal rhabdomyosarcoma in the left posterior buccal mucosa, with extension in the adjacent alveolus, soft palate, oropharynx and nasopharynx of a 17-year-old female. PMID:27721622

  3. In ovo electroporation in embryonic chick retina.

    PubMed

    Islam, Mohammed M; Doh, Sung Tae; Cai, Li

    2012-02-05

    Chicken embryonic retina is an excellent tool to study retinal development in higher vertebrates. Because of large size and external development, it is comparatively very easy to manipulate the chick embryonic retina using recombinant DNA/RNA technology. Electroporation of DNA/RNA constructs into the embryonic retina have a great advantage to study gene regulation in retinal stem/progenitor cells during retinal development. Different type of assays such as reporter gene assay, gene over-expression, gene knock down (shRNA) etc. can be performed using the electroporation technique. This video demonstrates targeted retinal injection and in ovo electroporation into the embryonic chick retina at the Hamburger and Hamilton stage 22-23, which is about embryonic day 4 (E4). Here we show a rapid and convenient in ovo electroporation technique whereby a plasmid DNA that expresses green fluorescent protein (GFP) as a marker is directly delivered into the chick embryonic subretinal space and followed by electric pulses to facilitate DNA uptake by retinal stem/progenitor cells. The new method of retinal injection and electroporation at E4 allows the visualization of all retinal cell types, including the late-born neurons(1), which has been difficult with the conventional method of injection and electroporation at E1.5(2).

  4. An amphioxus nodal gene (AmphiNodal) with early symmetrical expression in the organizer and mesoderm and later asymmetrical expression associated with left-right axis formation

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Linda Z.; Holland, Nicholas D.

    2002-01-01

    The full-length sequence and zygotic expression of an amphioxus nodal gene are described. Expression is first detected in the early gastrula just within the dorsal lip of the blastopore in a region of hypoblast that is probably comparable with the vertebrate Spemann's organizer. In the late gastrula and early neurula, expression remains bilaterally symmetrical, limited to paraxial mesoderm and immediately overlying regions of the neural plate. Later in the neurula stage, all neural expression disappears, and mesodermal expression disappears from the right side. All along the left side of the neurula, mesodermal expression spreads into the left side of the gut endoderm. Soon thereafter, all expression is down-regulated except near the anterior and posterior ends of the animal, where transcripts are still found in the mesoderm and endoderm on the left side. At this time, expression also begins in the ectoderm on the left side of the head, in the region where the mouth later forms. These results suggest that amphioxus and vertebrate nodal genes play evolutionarily conserved roles in establishing Spemann's organizer, patterning the mesoderm rostrocaudally and setting up the asymmetrical left-right axis of the body.

  5. Error estimation and adaptive order nodal method for solving multidimensional transport problems

    SciTech Connect

    Zamonsky, O.M.; Gho, C.J.; Azmy, Y.Y.

    1998-01-01

    The authors propose a modification of the Arbitrarily High Order Transport Nodal method whereby they solve each node and each direction using different expansion order. With this feature and a previously proposed a posteriori error estimator they develop an adaptive order scheme to automatically improve the accuracy of the solution of the transport equation. They implemented the modified nodal method, the error estimator and the adaptive order scheme into a discrete-ordinates code for solving monoenergetic, fixed source, isotropic scattering problems in two-dimensional Cartesian geometry. They solve two test problems with large homogeneous regions to test the adaptive order scheme. The results show that using the adaptive process the storage requirements are reduced while preserving the accuracy of the results.

  6. Self-energy of a nodal fermion in a d -wave superconductor

    NASA Astrophysics Data System (ADS)

    Chubukov, A. V.; Tsvelik, A. M.

    2006-06-01

    We reconsider the self-energy of a nodal (Dirac) fermion in a two-dimensional d -wave superconductor. A conventional belief is that ImΣ(ω,T)˜max(ω3,T3) . We show that Σ(ω,k,T) for k along the nodal direction is actually a complex function of ω,T , and the deviation from the mass shell. In particular, the second-order self-energy diverges at a finite T when either ω or k-kF vanish. We show that the full summation of infinite diagrammatic series recovers a finite result for Σ , but the full angle-resolved photoemission spectroscopy spectral function is nonmonotonic and has a kink whose location compared to the mass shell differs qualitatively for spin-and charge-mediated interactions.

  7. The General-Use Nodal Network Solver (GUNNS) Modeling Package for Space Vehicle Flow System Simulation

    NASA Technical Reports Server (NTRS)

    Harvey, Jason; Moore, Michael

    2013-01-01

    The General-Use Nodal Network Solver (GUNNS) is a modeling software package that combines nodal analysis and the hydraulic-electric analogy to simulate fluid, electrical, and thermal flow systems. GUNNS is developed by L-3 Communications under the TS21 (Training Systems for the 21st Century) project for NASA Johnson Space Center (JSC), primarily for use in space vehicle training simulators at JSC. It has sufficient compactness and fidelity to model the fluid, electrical, and thermal aspects of space vehicles in real-time simulations running on commodity workstations, for vehicle crew and flight controller training. It has a reusable and flexible component and system design, and a Graphical User Interface (GUI), providing capability for rapid GUI-based simulator development, ease of maintenance, and associated cost savings. GUNNS is optimized for NASA's Trick simulation environment, but can be run independently of Trick.

  8. The effect of viscosity on steady transonic flow with a nodal solution topology

    NASA Technical Reports Server (NTRS)

    Owocki, Stanley P.; Zank, Gary P.

    1991-01-01

    The effect of viscosity on a steady, transonic flow for which the inviscid limit has a nodal solution topology near the critical point is investigated. For the accelerating case, viscous solutions tend to repel each other, so that a very delicate choice of initial conditions is required to prevent them from diverging. Only the two critical solutions extend to arbitrarily large distances into both the subsonic and supersonic flows. For the decelerating case, the solutions tend to attract, and so an entire two-parameter family of solutions now extends over large distances. The general effect of viscosity on the solution degeneracy of a nodal topology is thus to reduce or limit it for the accelerating case and to enhance it for the decelerating case. The astrophysical implications of these findings are addressed.

  9. Normal State Spectral Lineshapes of Nodal Quasiparticles in Single Layer Bi2201 Superconductor

    SciTech Connect

    Lanzara, A.

    2010-04-30

    A detailed study of the normal state photoemission lineshapes and quasiparticle dispersion for the single layer Bi{sub 2}Sr{sub 2-x}La{sub x}CuO{sub 6+{delta}}(Bi2201) superconductor is presented. We report the first experimental evidence of a double peak structure and a dip of spectral intensity in the energy distribution curves (EDCs) along the nodal direction. The double peak structure is well identified in the normal state, up to ten times the critical temperature. As a result of the same self-energy effect, a strong mass renormalization of the quasiparticle dispersion, i.e. kink, and an increase of the quasiparticle lifetime in the normal state are also observed. Our results provide unambiguous evidence on the existence of bosonic excitation in the normal state, and support a picture where nodal quasiparticles are strongly coupled to the lattice.

  10. Cryopreservation of Passiflora pohlii nodal segments and assessment of genetic stability of regenerated plants.

    PubMed

    Merhy, T S M; Vianna, M G; Garcia, R O; Pacheco, G; Mansur, E

    2014-01-01

    Passiflora pohlii is a wild species native to Brazil, with a potential agronomic interest due to its tolerance to soil-borne pathogens that cause damage to the passion fruit culture, and could be used in breeding. Because this species occurs in impacted regions, the goal of this study was the development of in vitro conservation strategies, using nodal segments from axenic plants. Encapsulation-vitrification and vitrification techniques were tested for cryopreservation of nodal segments. The highest recovery (65%) was obtained with the vitrification technique using treatment with the PVS3 vitrification solution from 30 to 120 min. Post-rewarming recovery was achieved on MSM medium supplemented with 30.8 μM BAP with incubation in the dark for 30 days before transfer in the presence of light. No differences were detected between control and cryopreserved materials as assayed by RAPD and ISSR. PMID:24997838

  11. Error analysis of the quadratic nodal expansion method in slab geometry

    SciTech Connect

    Penland, R.C.; Turinsky, P.J.; Azmy, Y.Y.

    1994-10-01

    As part of an effort to develop an adaptive mesh refinement strategy for use in state-of-the-art nodal diffusion codes, the authors derive error bounds on the solution variables of the quadratic Nodal Expansion Method (NEM) in slab geometry. Closure of the system is obtained through flux discontinuity relationships and boundary conditions. In order to verify the analysis presented, the authors compare the quadratic NEM to the analytic solution of a test problem. The test problem for this investigation is a one-dimensional slab [0,20cm] with L{sup 2} = 6.495cm{sup 2} and D = 0.1429cm. The slab has a unit neutron source distributed uniformly throughout and zero flux boundary conditions. The analytic solution to this problem is used to compute the node-average fluxes over a variety of meshes, and these are used to compute the NEM maximum error on each mesh.

  12. Coherence Effects of Caroli-de Gennes-Matricon Modes in Nodal Topological Superconductors

    NASA Astrophysics Data System (ADS)

    Tsutsumi, Yasumasa; Kato, Yusuke

    2016-05-01

    Coherence effects by the impurity scattering of Caroli-de Gennes-Matricon (CdGM) modes in a vortex for nodal topological superconductors have been studied. The coherence effects reflect a topological number defined on a particular momentum space avoiding the superconducting gap nodes. First, we analytically derived the eigenvalue and eigenfunction of the CdGM modes, including the zero-energy modes, in a nodal topological superconducting state without impurities, where we focused on a possible superconducting state of UPt3 as an example. Then, we studied impurity effects on the CdGM modes by introducing the impurity self-energy, which are dominated by the coherence factor depending on the eigenfunction of the CdGM modes. For the zero-energy CdGM modes, the coherence factor vanishes in a certain momentum range, which is guaranteed by topological invariance characterized by the one-dimensional winding number.

  13. A Hybrid Nodal Method for Time-Dependent Incompressible Flow in Two-Dimensional Arbitrary Geometries

    SciTech Connect

    Toreja, A J; Uddin, R

    2002-10-21

    A hybrid nodal-integral/finite-analytic method (NI-FAM) is developed for time-dependent, incompressible flow in two-dimensional arbitrary geometries. In this hybrid approach, the computational domain is divided into parallelepiped and wedge-shaped space-time nodes (cells). The conventional nodal integral method (NIM) is applied to the interfaces between adjacent parallelepiped nodes (cells), while a finite analytic approach is applied to the interfaces between parallelepiped and wedge-shaped nodes (cells). In this paper, the hybrid method is formally developed and an application of the NI-FAM to fluid flow in an enclosed cavity is presented. Results are compared with those obtained using a commercial computational fluid dynamics code.

  14. miR-373 is regulated by TGFβ signaling and promotes mesendoderm differentiation in human Embryonic Stem Cells.

    PubMed

    Rosa, Alessandro; Papaioannou, Marilena D; Krzyspiak, Joanna E; Brivanlou, Ali H

    2014-07-01

    MicroRNAs (miRNAs) belonging to the evolutionary conserved miR-302 family play important functions in Embryonic Stem Cells (ESCs). The expression of some members, such as the human miR-302 and mouse miR-290 clusters, is regulated by ESC core transcription factors. However, whether miRNAs act downstream of signaling pathways involved in human ESC pluripotency remains unknown. The maintenance of pluripotency in hESCs is under the control of the TGFβ pathway. Here, we show that inhibition of the Activin/Nodal branch of this pathway affects the expression of a subset of miRNAs in hESCs. Among them, we found miR-373, a member of the miR-302 family. Proper levels of miR-373 are crucial for the maintenance of hESC pluripotency, since its overexpression leads to differentiation towards the mesendodermal lineage. Among miR-373 predicted targets, involved in TGFβ signaling, we validated the Nodal inhibitor Lefty. Our work suggests a crucial role for the interplay between miRNAs and signaling pathways in ESCs.

  15. Numerical divergence effects of equivalence theory in the nodal expansion method

    SciTech Connect

    Zika, M.R.; Downar, T.J. )

    1993-11-01

    Accurate solutions of the advanced nodal equations require the use of discontinuity factors (DFs) to account for the homogenization errors that are inherent in all coarse-mesh nodal methods. During the last several years, nodal equivalence theory (NET) has successfully been implemented for the Cartesian geometry and has received widespread acceptance in the light water reactor industry. The extension of NET to other reactor types has had limited success. Recent efforts to implement NET within the framework of the nodal expansion method have successfully been applied to the fast breeder reactor. However, attempts to apply the same methods to thermal reactors such as the Modular High-Temperature Gas Reactor (MHTGR) have led to numerical divergence problems that can be attributed directly to the magnitude of the DFs. In the work performed here, it was found that the numerical problems occur in the inner and upscatter iterations of the solution algorithm. These iterations use a Gauss-Seidel iterative technique that is always convergent for problems with unity DFs. However, for an MHTGR model that requires large DFs, both the inner and upscatter iterations were divergent. Initial investigations into methods for bounding the DFs have proven unsatisfactory as a means of remedying the convergence problems. Although the DFs could be bounded to yield a convergent solution, several cases were encountered where the resulting flux solution was less accurate than the solution without DFs. For the specific case of problems without upscattering, an alternate numerical method for the inner iteration, an LU decomposition, was identified and shown to be feasible.

  16. Nodal collocation approximation for the multidimensional PL equations applied to transport source problems

    SciTech Connect

    Verdu, G.; Capilla, M.; Talavera, C. F.; Ginestar, D.

    2012-07-01

    PL equations are classical high order approximations to the transport equations which are based on the expansion of the angular dependence of the angular neutron flux and the nuclear cross sections in terms of spherical harmonics. A nodal collocation method is used to discretize the PL equations associated with a neutron source transport problem. The performance of the method is tested solving two 1D problems with analytical solution for the transport equation and a classical 2D problem. (authors)

  17. Three-Dimensional Conformal Radiation Therapy for Esophageal Squamous Cell Carcinoma: Is Elective Nodal Irradiation Necessary?

    SciTech Connect

    Zhao Kuaile; Ma Jinbo; Liu Guang; Wu Kailiang; Shi Xuehui; Jiang Guoliang

    2010-02-01

    Purpose: To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. Methods and Materials: A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. Results: All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. Conclusions: In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems.

  18. Salvage therapy of small volume prostate cancer nodal failures: a review of the literature.

    PubMed

    De Bari, Berardino; Alongi, Filippo; Buglione, Michela; Campostrini, Franco; Briganti, Alberto; Berardi, Genoveffa; Petralia, Giuseppe; Bellomi, Massimo; Chiti, Arturo; Fodor, Andrei; Suardi, Nazareno; Cozzarini, Cesare; Nadia, Di Muzio; Scorsetti, Marta; Orecchia, Roberto; Montorsi, Francesco; Bertoni, Filippo; Magrini, Stefano Maria; Jereczek-Fossa, Barbara Alicja

    2014-04-01

    New imaging modalities may be useful to identify prostate cancer patients with small volume, limited nodal relapse ("oligo-recurrent") potentially amenable to local treatments (radiotherapy, surgery) with the aim of long-term control of the disease, even in a condition traditionally considered prognostically unfavorable. This report reviews the new diagnostic tools and the main published data about the role of surgery and radiation therapy in this particular subgroup of patients.

  19. Sentinel Node Identification Rate and Nodal Involvement in the EORTC 10981-22023 AMAROS Trial

    PubMed Central

    Meijnen, Philip; van Tienhoven, Geertjan; van de Velde, Cornelis J. H.; Mansel, Robert E.; Bogaerts, Jan; Duez, Nicole; Cataliotti, Luigi; Klinkenbijl, Jean H. G.; Westenberg, Helen A.; van der Mijle, Huub; Snoj, Marko; Hurkmans, Coen; Rutgers, Emiel J. T.

    2010-01-01

    Background The randomized EORTC 10981-22023 AMAROS trial investigates whether breast cancer patients with a tumor-positive sentinel node biopsy (SNB) are best treated with an axillary lymph node dissection (ALND) or axillary radiotherapy (ART). The aim of the current substudy was to evaluate the identification rate and the nodal involvement. Methods The first 2,000 patients participating in the AMAROS trial were evaluated. Associations between the identification rate and technical, patient-, and tumor-related factors were evaluated. The outcome of the SNB procedure and potential further nodal involvement was assessed. Results In 65 patients, the sentinel node could not be identified. As a result, the sentinel node identification rate was 97% (1,888 of 1,953). Variables affecting the success rate were age, pathological tumor size, histology, year of accrual, and method of detection. The SNB results of 65% of the patients (n = 1,220) were negative and the patients underwent no further axillary treatment. The SNB results were positive in 34% of the patients (n = 647), including macrometastases (n = 409, 63%), micrometastases (n = 161, 25%), and isolated tumor cells (n = 77, 12%). Further nodal involvement in patients with macrometastases, micrometastases, and isolated tumor cells undergoing an ALND was 41, 18, and 18%, respectively. Conclusions With a 97% detection rate in this prospective international multicenter study, the SNB procedure is highly effective, especially when the combined method is used. Further nodal involvement in patients with micrometastases and isolated tumor cells in the sentinel node was similar—both were 18%. PMID:20300966

  20. Atrioventricular Nodal Re-entry Tachycardia in Identical Twins: A Case Report and Literature Review.

    PubMed

    Barake, Walid; Caldwell, Jane; Baranchuk, Adrian

    2013-01-01

    This report details the case of 17 year old identical twins who both presented with paroxysmal supraventricular tachycardia (PSVT). Electrophysiological studies revealed atrioventricular nodal reentry tachycardia (AVNRT) in both twins. Successful but technically challenging slow pathway ablation was performed in both twins. This is the first reported case of confirmed AVNRT in identical twins which adds strong evidence to heritability of the dual AV node physiology and AVNRT. A review of the current literature regarding PSVT in monozygotic twins is provided. PMID:23329875

  1. EXTENSION OF THE 1D FOUR-GROUP ANALYTIC NODAL METHOD TO FULL MULTIGROUP

    SciTech Connect

    B. D. Ganapol; D. W. Nigg

    2008-09-01

    In the mid 80’s, a four-group/two-region, entirely analytical 1D nodal benchmark appeared. It was readily acknowledged that this special case was as far as one could go in terms of group number and still achieve an analytical solution. In this work, we show that by decomposing the solution to the multigroup diffusion equation into homogeneous and particular solutions, extension to any number of groups is a relatively straightforward exercise using the mathematics of linear algebra.

  2. Nodal soliton solutions for generalized quasilinear Schrödinger equations

    SciTech Connect

    Deng, Yinbin Peng, Shuangjie; Wang, Jixiu

    2014-05-15

    This paper is concerned with constructing nodal radial solutions for generalized quasilinear Schrödinger equations in R{sup N} which arise from plasma physics, fluid mechanics, as well as high-power ultashort laser in matter. For any given integer k ⩾ 0, by using a change of variables and minimization argument, we obtain a sign-changing minimizer with k nodes of a minimization problem.

  3. Atrioventricular Nodal Re-entry Tachycardia in Identical Twins: A Case Report and Literature Review

    PubMed Central

    Barake, Walid; Caldwell, Jane; Baranchuk, Adrian

    2013-01-01

    This report details the case of 17 year old identical twins who both presented with paroxysmal supraventricular tachycardia (PSVT). Electrophysiological studies revealed atrioventricular nodal reentry tachycardia (AVNRT) in both twins. Successful but technically challenging slow pathway ablation was performed in both twins. This is the first reported case of confirmed AVNRT in identical twins which adds strong evidence to heritability of the dual AV node physiology and AVNRT. A review of the current literature regarding PSVT in monozygotic twins is provided. PMID:23329875

  4. Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma

    PubMed Central

    Chen, Chuanben; Zhang, Mingwei; Xu, Yuanji; Yue, Qiuyuan; Bai, Penggang; Zhou, Lin; Xiao, Youping; Zheng, Dechun; Lin, Kongqi; Qiu, Sufang; Chen, Yunbin; Pan, Jianji

    2016-01-01

    Abstract The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma. Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements. Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (κ=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes. Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation. PMID:26945354

  5. The finite element absolute nodal coordinate formulation incorporated with surface stress effect to model elastic bending nanowires in large deformation

    NASA Astrophysics Data System (ADS)

    He, Jin; Lilley, Carmen M.

    2009-08-01

    Surface stress was incorporated into the finite element absolute nodal coordinate formulation in order to model elastic bending of nanowires in large deformation. The absolute nodal coordinate formulation is a numerical method to model bending structures in large deformation. The generalized Young-Laplace equation was employed to model the surface stress effect on bending nanowires. Effects from surface stress and large deformation on static bending nanowires are presented and discussed. The results calculated with the absolute nodal coordinate formulation incorporated with surface stress show that the surface stress effect makes the bending nanowires behave like softer or stiffer materials depending on the boundary condition. The surface stress effect diminishes as the dimensions of the bending structures increase beyond the nanoscale. The developed algorithm is consistent with the classical absolute nodal coordinate formulation at the macroscale.

  6. Nodal: master and commander of the dorsal-ventral and left-right axes in the sea urchin embryo.

    PubMed

    Molina, M Dolores; de Crozé, Noémie; Haillot, Emmanuel; Lepage, Thierry

    2013-08-01

    Recent studies suggest that specification of the dorsal-ventral and left-right axes of the sea urchin embryo relies on Nodal-expressing signalling centres located in the ventral ectoderm and in the archenteron that share striking similarities with vertebrate organising centres. Nodal and its downstream target BMP2/4 pattern all three germ layers along the dorsal-ventral axis, repress neural fates and control morphogenesis of the larva. Moreover, Nodal establishes left-right asymmetry by repressing formation of the adult rudiment and inhibiting germline cells differentiation on the right side, while BMP2/4 promotes expression of mesodermal genes on the left side. These findings provide a framework for future studies and raise new questions regarding the events upstream and downstream of Nodal and BMP signalling during axis formation. PMID:23769944

  7. Formin DAAM1 Organizes Actin Filaments in the Cytoplasmic Nodal Actin Network

    PubMed Central

    Luo, Weiwei; Lieu, Zi Zhao; Manser, Ed; Bershadsky, Alexander D.; Sheetz, Michael P.

    2016-01-01

    A nodal cytoplasmic actin network underlies actin cytoplasm cohesion in the absence of stress fibers. We previously described such a network that forms upon Latrunculin A (LatA) treatment, in which formin DAAM1 was localized at these nodes. Knock down of DAAM1 reduced the mobility of actin nodes but the nodes remained. Here we have investigated DAAM1 containing nodes after LatA washout. DAAM1 was found to be distributed between the cytoplasm and the plasma membrane. The membrane binding likely occurs through an interaction with lipid rafts, but is not required for F-actin assembly. Interesting the forced interaction of DAAM1 with plasma membrane through a rapamycin-dependent linkage, enhanced F-actin assembly at the cell membrane (compared to the cytoplasm) after the LatA washout. However, immediately after addition of both rapamycin and LatA, the cytoplasmic actin nodes formed transiently, before DAAM1 moved to the membrane. This was consistent with the idea that DAAM1 was initially anchored to cytoplasmic actin nodes. Further, photoactivatable tracking of DAAM1 showed DAAM1 was immobilized at these actin nodes. Thus, we suggest that DAAM1 organizes actin filaments into a nodal complex, and such nodal complexes seed actin network recovery after actin depolymerization. PMID:27760153

  8. A coarse-mesh nodal method-diffusive-mesh finite difference method

    SciTech Connect

    Joo, H.; Nichols, W.R.

    1994-05-01

    Modern nodal methods have been successfully used for conventional light water reactor core analyses where the homogenized, node average cross sections (XSs) and the flux discontinuity factors (DFs) based on equivalence theory can reliably predict core behavior. For other types of cores and other geometries characterized by tightly-coupled, heterogeneous core configurations, the intranodal flux shapes obtained from a homogenized nodal problem may not accurately portray steep flux gradients near fuel assembly interfaces or various reactivity control elements. This may require extreme values of DFs (either very large, very small, or even negative) to achieve a desired solution accuracy. Extreme values of DFs, however, can disrupt the convergence of the iterative methods used to solve for the node average fluxes, and can lead to a difficulty in interpolating adjacent DF values. Several attempts to remedy the problem have been made, but nothing has been satisfactory. A new coarse-mesh nodal scheme called the Diffusive-Mesh Finite Difference (DMFD) technique, as contrasted with the coarse-mesh finite difference (CMFD) technique, has been developed to resolve this problem. This new technique and the development of a few-group, multidimensional kinetics computer program are described in this paper.

  9. A two-dimensional shear deformable beam element based on the absolute nodal coordinate formulation

    NASA Astrophysics Data System (ADS)

    Dufva, K. E.; Sopanen, J. T.; Mikkola, A. M.

    2005-02-01

    In this study, a new two-dimensional shear deformable beam element is proposed for large deformation problems. The kinematics of the beam are defined using an exact displacement field, where the rotation angles of the cross-section caused by bending and shear deformations are described separately. Cubic interpolation is used for determining the curvature of the beam due to bending, while linear interpolation polynomials are used for the shear strain. The absolute nodal coordinate formulation, in which global displacements and slopes are used as the nodal coordinates, is employed for the finite element discretization of the beam. The capability of the element to predict static deformation is studied using numerical examples. The results imply that the element is free of a phenomenon called shear-locking. The capability of the element to model highly nonlinear behaviour is established using a bending test where the cantilever is bent into a full circle using only four elements. A flexible pendulum and a spin-up manoeuvre are modelled in order to study the behaviour of the element in dynamical problems. The proposed element is also compared with an existing shear deformable beam element based on the absolute nodal coordinate formulation. Finally, the simple linearization of the beam curvature based on the assumption of small strain will be discussed.

  10. Nodal Liquid Theory of the Pseudo-Gap Phase of High-Tc Superconductors

    NASA Astrophysics Data System (ADS)

    Balents, Leon; Fisher, Matthew P. A.; Nayak, Chetan

    We introduce and study the nodal liquid, a novel zero-temperature quantum phase obtained by quantum-disordering a d-wave superconductor. It has numerous remarkable properties which lead us to suggest it as an explanation of the pseudo-gap state in underdoped high-temperature superconductors. In the absence of impurities, these include power-law magnetic order, a T-linear spin susceptibility, nontrivial thermal conductivity, and two- and one-particle charge gaps, the latter evidenced, e.g. in transport and electron photoemission (which exhibits pronounced fourfold anisotropy inherited from the d-wave quasiparticles). We use a (2+1)-dimensional duality transformation to derive an effective field theory for this phase. The theory is comprised of gapless neutral Dirac particles living at the former d-wave nodes, weakly coupled to the fluctuating gauge field of a dual Ginzburg-Landau theory. The nodal liquid interpolates naturally between the d-wave superconductor and the insulating antiferromagnet, and our effective field theory is powerful enough to permit a detailed analysis of a panoply of interesting phenomena, including charge ordering, antiferromagnetism, and d-wave superconductivity. We also discuss the zero-temperature quantum phase transitions which separate the nodal liquid from various ordered phases.

  11. Some results of a nodal method for nonlinear space-time reactor dynamics

    SciTech Connect

    Le, T.T.; Grossman, L.M.

    1991-12-31

    There are many reports about nodal methods for static and dynamic problems, but not many for the nonlinear feedback cases. In this paper, a class of nodal methods called ``mathematical nodal method`` (MNM) is studied with the temperature feedback problems. The spatially complex domain of the problem is represented as a collection of geometrically simple subdomains of the size of fuel assemblies called nodes. Over each node, the time dependent coefficients of the neutron flux, precursor concentrations, fuel and coolant temperatures are the surface and volume weighted average (moment) values of the unknown solutions; the space dependent basis functions are a combination of Legendre polynomials. If the material parameters are a linear function of fuel and coolant temperatures, the coupled equations can be put in a dimensionless form and a system of time dependent ordinary differential equations containing nonlinear feedback terms is obtained. These nonlinear feedback terms are updated at each time step during the time iteration process. Results of some benchmark problems are included in this report.

  12. Some results of a nodal method for nonlinear space-time reactor dynamics

    SciTech Connect

    Le, T.T. ); Grossman, L.M. . Dept. of Nuclear Engineering)

    1991-01-01

    There are many reports about nodal methods for static and dynamic problems, but not many for the nonlinear feedback cases. In this paper, a class of nodal methods called mathematical nodal method'' (MNM) is studied with the temperature feedback problems. The spatially complex domain of the problem is represented as a collection of geometrically simple subdomains of the size of fuel assemblies called nodes. Over each node, the time dependent coefficients of the neutron flux, precursor concentrations, fuel and coolant temperatures are the surface and volume weighted average (moment) values of the unknown solutions; the space dependent basis functions are a combination of Legendre polynomials. If the material parameters are a linear function of fuel and coolant temperatures, the coupled equations can be put in a dimensionless form and a system of time dependent ordinary differential equations containing nonlinear feedback terms is obtained. These nonlinear feedback terms are updated at each time step during the time iteration process. Results of some benchmark problems are included in this report.

  13. A Computational Model of Dynein Activation Patterns that Can Explain Nodal Cilia Rotation

    PubMed Central

    Chen, Duanduan; Zhong, Yi

    2015-01-01

    Normal left-right patterning in vertebrates depends on the rotational movement of nodal cilia. In order to produce this ciliary motion, the activity of axonemal dyneins must be tightly regulated in a temporal and spatial manner; the specific activation pattern of the dynein motors in the nodal cilia has not been reported. Contemporary imaging techniques cannot directly assess dynein activity in a living cilium. In this study, we establish a three-dimensional model to mimic the ciliary ultrastructure and assume that the activation of dynein proteins is related to the interdoublet distance. By employing finite-element analysis and grid deformation techniques, we simulate the mechanical function of dyneins by pairs of point loads, investigate the time-variant interdoublet distance, and simulate the dynein-triggered ciliary motion. The computational results indicate that, to produce the rotational movement of nodal cilia, the dynein activity is transferred clockwise (looking from the tip) between the nine doublet microtubules, and along each microtubule, the dynein activation should occur faster at the basal region and slower when it is close to the ciliary tip. Moreover, the time cost by all the dyneins along one microtubule to be activated can be used to deduce the dynein activation pattern; it implies that, as an alternative method, measuring this time can indirectly reveal the dynein activity. The proposed protein-structure model can simulate the ciliary motion triggered by various dynein activation patterns explicitly and may contribute to furthering the studies on axonemal dynein activity. PMID:26153700

  14. Primary nodal peripheral T-cell lymphomas: diagnosis and therapeutic considerations

    PubMed Central

    Lage, Luis Alberto de Pádua Covas; Cabral, Tamara Carvalho dos Santos; Costa, Renata de Oliveira; Gonçalves, Marianne de Castro; Levy, Debora; Zerbini, Maria Cláudia Nogueira; Pereira, Juliana

    2015-01-01

    Nodal peripheral T-cell lymphomas are a rare group of neoplasms derived from post-thymic and activated T lymphocytes. A review of scientific articles listed in PubMed, Lilacs, and the Cochrane Library databases was performed using the term “peripheral T-cell lymphomas”. According to the World Health Organization classification of hematopoietic tissue tumors, this group of neoplasms consists of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase positive (ALCL-ALK+), and a provisional entity called anaplastic large cell lymphoma-anaplastic lymphoma kinase negative (ALCL-ALK−). Because the treatment and prognoses of these neoplasms involve different principles, it is essential to distinguish each one by its clinical, immunophenotypic, genetic, and molecular features. Except for anaplastic large cell lymphoma-anaplastic lymphoma kinase positive, which has no adverse international prognostic index, the prognosis of nodal peripheral T-cell lymphomas is worse than that of aggressive B-cell lymphomas. Chemotherapy based on anthracyclines provides poor outcomes because these neoplasms frequently have multidrug-resistant phenotypes. Based on this, the current tendency is to use intensified cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP) regimens with the addition of new drugs, and autologous hematopoietic stem cell transplantation. This paper describes the clinical features and diagnostic methods, and proposes a therapeutic algorithm for nodal peripheral T-cell lymphoma patients. PMID:26190436

  15. A computational model of dynein activation patterns that can explain nodal cilia rotation.

    PubMed

    Chen, Duanduan; Zhong, Yi

    2015-07-01

    Normal left-right patterning in vertebrates depends on the rotational movement of nodal cilia. In order to produce this ciliary motion, the activity of axonemal dyneins must be tightly regulated in a temporal and spatial manner; the specific activation pattern of the dynein motors in the nodal cilia has not been reported. Contemporary imaging techniques cannot directly assess dynein activity in a living cilium. In this study, we establish a three-dimensional model to mimic the ciliary ultrastructure and assume that the activation of dynein proteins is related to the interdoublet distance. By employing finite-element analysis and grid deformation techniques, we simulate the mechanical function of dyneins by pairs of point loads, investigate the time-variant interdoublet distance, and simulate the dynein-triggered ciliary motion. The computational results indicate that, to produce the rotational movement of nodal cilia, the dynein activity is transferred clockwise (looking from the tip) between the nine doublet microtubules, and along each microtubule, the dynein activation should occur faster at the basal region and slower when it is close to the ciliary tip. Moreover, the time cost by all the dyneins along one microtubule to be activated can be used to deduce the dynein activation pattern; it implies that, as an alternative method, measuring this time can indirectly reveal the dynein activity. The proposed protein-structure model can simulate the ciliary motion triggered by various dynein activation patterns explicitly and may contribute to furthering the studies on axonemal dynein activity.

  16. A coarse-mesh nodal method, the diffusive-mesh finite difference method

    SciTech Connect

    Joo, H.; Nichols, W.R.

    1994-12-31

    Modern nodal methods have been successfully used for conventional light water reactor core analyses where the homogenized, node average cross section (XSs) and the flux discontinuity factors (DFs) based on equivalence theory can reliably predict core behavior. For other types of cores and other geometries characterized by tightly coupled, heterogeneous core configurations, the intranodal flux shapes obtained from a homogenized nodal problem may not accurately portray steep flux gradients near fuel assembly interfaces or various reactivity control elements. This may require extreme values of DFs (either very large, very small, or even negative) to achieve a desired solution accuracy. Extreme values of DFs, however, can disrupt the convergence of the iterative methods used to solve for the node average fluxes and can lead to difficulty in interpolating adjacent DF values. Several attempts to remedy the problem have been made, but nothing has been satisfactory. A new coarse-mesh nodal scheme called the diffusive-mesh finite difference (DMFD) technique, as contrasted with the coarse-mesh finite difference (CMFD) technique, has been developed to resolve this problem. This new technique and the development of a few-group, multidimensional kinetics computer program are described in this paper.

  17. Potential Pitfall in the Assessment of Lung Cancer with FDG-PET/CT: Talc Pleurodesis Causes Intrathoracic Nodal FDG Avidity

    PubMed Central

    Carter, Brett W.; Muse, Victorine; Digumarthy, Subba; Shepard, Jo-Anne; Sharma, Amita

    2013-01-01

    Objective. Talc pleurodesis is a common procedure performed to treat complications related to lung cancer. The purpose of our study was to characterize any thoracic nodal findings on FDG PET/CT associated with prior talc pleurodesis. Materials and Methods. The electronic medical record identified 44 patients who underwent PET/CT between January 2006 and December 2010 and had a history of talc pleurodesis. For each exam, we evaluated the distribution pattern, size, and attenuation of intrathoracic lymph nodes and the associated standardized uptake value. Results. High-attenuation intrathoracic lymph nodes were noted in 11 patients (25%), and all had corresponding increased FDG uptake (range 2–9 mm). Involved nodal groups were anterior peridiaphragmatic (100%), paracardiac (45%), internal mammary (25%), and peri-IVC (18%) nodal stations. Seven of the 11 patients (63%) had involvement of multiple lymph nodal groups. Mean longitudinal PET/CT and standalone CT followups of 15 ± 11 months showed persistence of both high-attenuation and increased uptake at these sites, without increase in nodal size suggesting metastatic disease involvement. Conclusions. FDG avid, high-attenuation lymph nodes along the lymphatic drainage pathway for parietal pleura are a relatively common finding following talc pleurodesis and should not be mistaken for nodal metastases during the evaluation of patients with history of lung cancer. PMID:26316941

  18. Uncoupled Embryonic and Extra-Embryonic Tissues Compromise Blastocyst Development after Somatic Cell Nuclear Transfer

    PubMed Central

    Degrelle, Séverine A.; Jaffrezic, Florence; Campion, Evelyne; Lê Cao, Kim-Anh; Le Bourhis, Daniel; Richard, Christophe; Rodde, Nathalie; Fleurot, Renaud; Everts, Robin E.; Lecardonnel, Jérôme; Heyman, Yvan; Vignon, Xavier; Tian, Xiuchun C.; Lewin, Harris A.; Renard, Jean-Paul; Hue, Isabelle

    2012-01-01

    Somatic cell nuclear transfer (SCNT) is the most efficient cell reprogramming technique available, especially when working with bovine species. Although SCNT blastocysts performed equally well or better than controls in the weeks following embryo transfer at Day 7, elongation and gastrulation defects were observed prior to implantation. To understand the developmental implications of embryonic/extra-embryonic interactions, the morphological and molecular features of elongating and gastrulating tissues were analysed. At Day 18, 30 SCNT conceptuses were compared to 20 controls (AI and IVP: 10 conceptuses each); one-half of the SCNT conceptuses appeared normal while the other half showed signs of atypical elongation and gastrulation. SCNT was also associated with a high incidence of discordance in embryonic and extra-embryonic patterns, as evidenced by morphological and molecular “uncoupling”. Elongation appeared to be secondarily affected; only 3 of 30 conceptuses had abnormally elongated shapes and there were very few differences in gene expression when they were compared to the controls. However, some of these differences could be linked to defects in microvilli formation or extracellular matrix composition and could thus impact extra-embryonic functions. In contrast to elongation, gastrulation stages included embryonic defects that likely affected the hypoblast, the epiblast, or the early stages of their differentiation. When taking into account SCNT conceptus somatic origin, i.e. the reprogramming efficiency of each bovine ear fibroblast (Low: 0029, Med: 7711, High: 5538), we found that embryonic abnormalities or severe embryonic/extra-embryonic uncoupling were more tightly correlated to embryo loss at implantation than were elongation defects. Alternatively, extra-embryonic differences between SCNT and control conceptuses at Day 18 were related to molecular plasticity (high efficiency/high plasticity) and subsequent pregnancy loss. Finally, because it alters

  19. Measuring the micromechanical properties of embryonic tissues.

    PubMed

    Chevalier, Nicolas R; Gazguez, Elodie; Dufour, Sylvie; Fleury, Vincent

    2016-02-01

    Local mechanical properties play an important role in directing embryogenesis, both at the cell (differentiation, migration) and tissue level (force transmission, organ formation, morphogenesis). Measuring them is a challenge as embryonic tissues are small (μm to mm) and soft (0.1-10 kPa). We describe here how glass fiber cantilevers can be fabricated, calibrated and used to apply small forces (0.1-10 μN), measure contractile activity and assess the bulk tensile elasticity of embryonic tissue. We outline how pressure (hydrostatic or osmotic) can be applied to embryonic tissue to quantify stiffness anisotropy. These techniques can be assembled at low cost and with a minimal amount of equipment. We then present a protocol to prepare tissue sections for local elasticity and adhesion measurements using the atomic force microscope (AFM). We compare AFM nanoindentation maps of native and formaldehyde fixed embryonic tissue sections and discuss how the local elastic modulus obtained by AFM compares to that obtained with other bulk measurement methods. We illustrate all of the techniques presented on the specific example of the chick embryonic digestive tract, emphasizing technical issues and common pitfalls. The main purpose of this report is to make these micromechanical measurement techniques accessible to a wide community of biologists and biophysicists.

  20. Scaffolding for Three-Dimensional Embryonic Vasculogenesis

    NASA Astrophysics Data System (ADS)

    Kraehenbuehl, Thomas P.; Aday, Sezin; Ferreira, Lino S.

    Biomaterial scaffolds have great potential to support efficient vascular differentiation of embryonic stem cells. Vascular cell fate-specific biochemical and biophysical cues have been identified and incorporated into three-dimensional (3D) biomaterials to efficiently direct embryonic vasculogenesis. The resulting vascular-like tissue can be used for regenerative medicine applications, further elucidation of biophysical and biochemical cues governing vasculogenesis, and drug discovery. In this chapter, we give an overview on the following: (1) developmental cues for directed differentiation of human embryonic stem cells (hESCs) into vascular cells, (2) 3D vascular differentiation in embryoid bodies (EBs), (3) preparation of 3D scaffolds for the vascular differentiation of hESCs, and (4) the most significant studies combining scaffolding and hESCs for development of vascular-like tissue.

  1. TGF-β Signaling in Stem Cell Regulation.

    PubMed

    Li, Wenlin; Wei, Wanguo; Ding, Sheng

    2016-01-01

    The transforming growth factor-β (TGF-β) family of cytokines, including TGF-β, bone morphogenic proteins (BMPs), and activin/nodal, is a group of crucial morphogens in embryonic development, and plays key roles in modulating stem/progenitor cell fate. TGF-β signaling is essential in maintaining the pluripotency of human pluripotent stem cells (hPSCs), including both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), and its modulation can direct lineage-specific differentiation. Recent studies also demonstrate TGF-β signaling negatively regulates reprogramming and inhibition of TGF-β signaling can enhance reprogramming through facilitating mesenchymal-to-epithelial transition (MET). This chapter introduces methods of modulating somatic cell reprogramming to iPSCs and neural induction from hPSCs through modulating TGF-β signaling by chemical approaches.

  2. Embryonic Stem Cell Patents and Human Dignity

    PubMed Central

    Resnik, David B.

    2009-01-01

    This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. PMID:17922198

  3. Regional Nodal Recurrence After Breast Conservation Treatment With Radiotherapy for Women With Early-Stage Breast Carcinoma

    SciTech Connect

    Lukens, J. Nicholas Vapiwala, Neha; Hwang, W.-T.; Solin, Lawrence J.

    2009-04-01

    Purpose: To report the long-term outcomes for women presenting with regional lymph node recurrence after breast conservation treatment with radiotherapy for Stage I and II invasive breast carcinoma. Methods and Materials: Of the women with pathologic Stage I and II invasive breast carcinoma treated with breast conservation treatment at University of Pennsylvania, 29 developed regional nodal recurrence as their first site of failure. An analysis of the patterns of regional nodal recurrence and their prognosis after recurrence was undertaken. The median follow-up from regional nodal recurrence was 5.4 years. Results: The pattern of regional nodal recurrence was as follows: 14 (48%) with simultaneous local and axillary recurrence, 7 (24%) with recurrence in the axilla only, 5 (17%) with recurrence in the supraclavicular region only, and 3 (10%) with multiple nodal sites of recurrence. For the entire study group, the 5-, 10-, and 15-year overall survival rate was 70%, 37%, and 28%, respectively. The 10-year overall survival rate for patients with locoregional recurrence was 32% compared with 45% for patients with regional-only recurrence (p = 0.50). The 10-year overall survival rate for patients with axillary recurrence discovered on pathologic examination of the mastectomy specimen was 31% compared with 42% for patients with palpable regional lymphadenopathy (p = 0.83). Conclusion: Patients with regional nodal recurrence after breast conservation treatment with radiotherapy for early-stage breast carcinoma are potentially salvageable. The prognosis after regional nodal recurrence was not significantly different when stratified by the presence or absence of simultaneous in-breast recurrence or the method of detection.

  4. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase.

    PubMed

    Sorescu, George P; Song, Hannah; Tressel, Sarah L; Hwang, Jinah; Dikalov, Sergey; Smith, Debra A; Boyd, Nolan L; Platt, Manu O; Lassègue, Bernard; Griendling, Kathy K; Jo, Hanjoong

    2004-10-15

    Atherosclerosis is an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions including oscillatory shear stress (OS). OS exposure induces endothelial expression of bone morphogenic protein 4 (BMP4), which in turn may activate intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesion. OS is also known to induce monocyte adhesion by producing reactive oxygen species (ROS) from reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, raising the possibility that BMP4 may stimulate the inflammatory response by ROS-dependent mechanisms. Here we show that ROS scavengers blocked ICAM-1 expression and monocyte adhesion induced by BMP4 or OS in endothelial cells (ECs). Similar to OS, BMP4 stimulated H2O2 and O2- production in ECs. Next, we used ECs obtained from p47phox-/- mice (MAE-p47-/-), which do not produce ROS in response to OS, to determine the role of NADPH oxidases. Similar to OS, BMP4 failed to induce monocyte adhesion in MAE-p47-/-, but it was restored when the cells were transfected with p47phox plasmid. Moreover, OS-induced O2- production was blocked by noggin (a BMP antagonist), suggesting a role for BMP. Furthermore, OS increased gp91phox (nox2) and nox1 mRNA levels while decreasing nox4. In contrast, BMP4 induced nox1 mRNA expression, whereas nox2 and nox4 were decreased or not affected, respectively. Also, OS-induced monocyte adhesion was blocked by knocking down nox1 with the small interfering RNA (siRNA). Finally, BMP4 siRNA inhibited OS-induced ROS production and monocyte adhesion. Together, these results suggest that BMP4 produced in ECs by OS stimulates ROS release from the nox1-dependent NADPH oxidase leading to inflammation, a critical early atherogenic step. PMID:15388638

  5. Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

    PubMed Central

    Liu, Yun; Deng, Li-Zhi; Sun, Hai-Peng; Xu, Jia-Yun; Li, Yi-Ming; Xie, Xin; Zhang, Li-Ming; Deng, Fei-Long

    2016-01-01

    Objective To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2). Methods Three groups of PlGF-2/BMP-2-loaded heparin–N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 μg PlGF-2; with 1.0 μg BMP-2; and with 0.5 μg PlGF-2 combined with 1.0 μg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays. Results The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%–84% of PlGF-2 and 89%–91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function. Conclusion PlGF-2-loaded heparin–HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone. PMID:27042064

  6. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

    SciTech Connect

    Biver, Emmanuel; Soubrier, Anne-Sophie; Thouverey, Cyril; Cortet, Bernard; Broux, Odile; Caverzasio, Joseph; Hardouin, Pierre

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.

  7. Correlating the effects of bone morphogenic protein to secreted soluble factors from fibroblasts and mesenchymal stem cells in regulating regenerative processes in vitro.

    PubMed

    Lynch, Kristen M; Ahsan, Tabassum

    2014-12-01

    The capacity to regenerate complex tissue structures after amputation in humans is limited to the digit tip. In a comparable mouse digit model, which includes both distal regeneration-competent and proximal regeneration-incompetent regions, successful regeneration involves precise orchestration of complex microenvironmental cues, including paracrine signaling via heterogeneous cell-cell interactions. Initial cellular processes, such as proliferation and migration, are critical in the formation of an initial stable cell mass and the ultimate regenerative outcome. Hence, the objective of these in vitro studies was to investigate the effect of soluble factors secreted by fibroblasts and mesenchymal stem cells (MSCs) on the proliferation and migration of cells from the regeneration-competent (P3) and -incompetent (P2) regions of the mouse digit tip. We found that P2 and P3 cells were more responsive to fibroblasts than MSCs and that the effects were mediated by bi-directional communication. To initiate understanding of the specific soluble factors that may be involved in the fibroblast-mediated changes in migration of P2 and P3 cells, bone morphogenic protein 2 (BMP2) was exogenously added to the medium. We found that changes in migration of P3 cells were similar when exposed to BMP2 or co-cultured with fibroblasts, indicating that BMP signaling may be responsible for the migratory response of P3 cells to the presence of fibroblasts. Furthermore, BMP2 expression in fibroblasts was shown to be responsive to tensile strain, as is present during wound closure. Therefore, these in vitro studies indicate that regenerative processes may be regulated by fibroblast-secreted soluble factors, which, in turn, are modulated by both cross-talk between heterogeneous phenotypes and the physical microenvironment of the healing site.

  8. Correlating the Effects of Bone Morphogenic Protein to Secreted Soluble Factors from Fibroblasts and Mesenchymal Stem Cells in Regulating Regenerative Processes In Vitro

    PubMed Central

    Lynch, Kristen M.

    2014-01-01

    The capacity to regenerate complex tissue structures after amputation in humans is limited to the digit tip. In a comparable mouse digit model, which includes both distal regeneration-competent and proximal regeneration-incompetent regions, successful regeneration involves precise orchestration of complex microenvironmental cues, including paracrine signaling via heterogeneous cell–cell interactions. Initial cellular processes, such as proliferation and migration, are critical in the formation of an initial stable cell mass and the ultimate regenerative outcome. Hence, the objective of these in vitro studies was to investigate the effect of soluble factors secreted by fibroblasts and mesenchymal stem cells (MSCs) on the proliferation and migration of cells from the regeneration-competent (P3) and -incompetent (P2) regions of the mouse digit tip. We found that P2 and P3 cells were more responsive to fibroblasts than MSCs and that the effects were mediated by bi-directional communication. To initiate understanding of the specific soluble factors that may be involved in the fibroblast-mediated changes in migration of P2 and P3 cells, bone morphogenic protein 2 (BMP2) was exogenously added to the medium. We found that changes in migration of P3 cells were similar when exposed to BMP2 or co-cultured with fibroblasts, indicating that BMP signaling may be responsible for the migratory response of P3 cells to the presence of fibroblasts. Furthermore, BMP2 expression in fibroblasts was shown to be responsive to tensile strain, as is present during wound closure. Therefore, these in vitro studies indicate that regenerative processes may be regulated by fibroblast-secreted soluble factors, which, in turn, are modulated by both cross-talk between heterogeneous phenotypes and the physical microenvironment of the healing site. PMID:24851900

  9. General Information about Childhood Central Nervous System Embryonal Tumors

    MedlinePlus

    ... System Embryonal Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System Embryonal Tumors Go ... in patients with a high-risk tumor. The information from tests and procedures done to detect (find) ...

  10. NodalB{copyright}: A unique program for optimum production of sucker rod pumping oil wells

    SciTech Connect

    Guirados, C.D.; Ercolino, J.M.; Sandoval, J.L.

    1995-12-31

    Sucker rod pumping is the oldest artificial lift method used in production of oil wells. This method is usually designed and analyzed with the assistance of programs based on simplified models, such as the API RP 11L, or with a wave equation simulator. In many cases, however, a technique that permits consideration of the inflow and outflow performance of the well is a more efficient way to design and analyze an oil well. This technique, referred to as Total Analysis or System Analysis (SA), has been successfully applied to flowing and artificially lifted wells. This paper presents a computer program developed by Intevep S.A., called NodalB{copyright}, created to perform the SA of sucker rod pumping wells. NodalB{copyright}`s unique characteristics make it a competitive program in today`s market of design and optimization software. This program allows consideration of the inflow performance of the reservoir depending on the drilling scheme, either vertical or horizontal, and determination of the sensitivity of the rod pumping system to its most relevant parameters, such as: pumping speed and stroke, pump diameter, gas oil ratio, gas separation efficiency, tubing diameter, pump depth, rod string design, oil viscosity, injected diluent (diesel, kerosene, etc.) ratio, water cut, reservoir pressure, productivity index, and different production schemes (i.e. production through the tubing or through the casing-tubing annulus). These features show the power of this program as a predictive tool. NodalB{copyright} is specially applicable to design, optimization and troubleshooting of heavy and viscous oil wells, taking into account the viscosity effects in the rod pumping system.

  11. Plant regeneration from single-nodal-stem explants of legume tree Prosopis alba Griseb.

    PubMed

    Castillo de Meier, G; Bovo, O A

    2000-08-01

    Seeds of Prosopis alba were scarified with abrasive paper and placed to germinate on MS (Murashige and Skoog 1962) nutrient medium. After 7 days of culture, the basal part of cotyledons was removed and pieces of 4 mm" from distal parts were cultured on Murashige and Skoog (1962) mineral salts and vitamins (MS) (3% sucrose) supplemented with growth regulators. Callus proliferation took place in the majority of the media tested. A low percentage of calluses with green buds that developed on MS basal medium containing 0.1 mg.L-1 2,4-D alone or supplemented with BAP at 0.1 mg.L-1 was observed. Neither cotyledonary segments in any medium assayed regenerated the whole plants. Bud elongation (near 70%) was achieved when single-nodal-stem segments cut from 20 days old seedlings were cultured on MS salts supplemented with 3 mg.L-1 NAA or 3 mg.L-1 IBA combined with 0.05 mg.L-1 KIN after 60 days in culture. Multiple shoots per bud were also observed. Single-nodal-stem segments from five-year-old plants were also cultured on the same media used for seedling explants. Maximal frequency of explants with bud elongation (near 70%) was found on MS with 0.1 mg.L-1 NAA plus 1 mg.L-1 BAP after 60 days of culture. Single-nodal-stem explants cut from adult trees (more than 20 years) were also employed, but the number of bud elongation was lesser. For rooting, the elongated shoots were transferred to a semisolid or liquid MS culture medium employing a paper bridge, supplemented with 0.5 mg.L-1 IBA or 0.1 mg.L-1 NAA.

  12. Optimal three-dimensional reusable tug trajectories for planetary missions including correction for nodal precession

    NASA Technical Reports Server (NTRS)

    Borsody, J.

    1976-01-01

    Equations are derived by using the maximum principle to maximize the payload of a reusable tug for planetary missions. The analysis includes a correction for precession of the space shuttle orbit. The tug returns to this precessed orbit (within a specified time) and makes the required nodal correction. A sample case is analyzed that represents an inner planet mission as specified by a fixed declination and right ascension of the outgoing asymptote and the mission energy. The reusable stage performance corresponds to that of a typical cryogenic tug. Effects of space shuttle orbital inclination, several trajectory parameters, and tug thrust on payload are also investigated.

  13. [Successful ablation of an atrioventricular nodal reentrant tachycardia ablation 2 years after orthotopic heart transplantation].

    PubMed

    Bellmann, Barbara; Reith, Sebastian; Gemein, Christopher; Schauerte, Patrick

    2015-09-01

    We report the case of a 48-year-old woman with an orthotopic heart transplantation. Two years after transplantation, the patient reported intermittent palpitations and dyspnea. The results of the 12-lead electrogram provided suspicion of AV nodal reentrant tachycardia (AVNRT), which was confirmed in the electrophysiological examination. The AVNRT was successfully eliminated without complications by radiofrequency catheter ablation of the slow pathway. The case shows that an AVNRT, even with existing sinus rhythm of the original heart, can also occur on the transplanted heart and ablation is safe and feasible. PMID:26208808

  14. Theoretical basis of the linear nodal and linear characteristic methods in the TORT computer code

    SciTech Connect

    Childs, R.L.; Rhoades, W.A.

    1993-01-01

    Novel numerical procedures for solving the Boltzmann equation have been added to the Three Dimensional Oak Ridge Discrete Ordinates Transport Code (TORT). These procedures produce much more accuracy in theflux solutions for a given mesh size, or allow a smaller mesh to be used in order to reduce costs. The first method is a special adaptation of the linear nodal method proposed by Walters and O'Dell. The basic method has been extensively adapted in order to avoid numerical distortions that may occur in shielding problems. The second method is a characteristic procedure with linear expansion of sources and boundary flows. These methods are in widespread use in the TORT code.

  15. Theoretical basis of the linear nodal and linear characteristic methods in the TORT computer code

    SciTech Connect

    Childs, R.L.; Rhoades, W.A.

    1993-01-01

    Novel numerical procedures for solving the Boltzmann equation have been added to the Three Dimensional Oak Ridge Discrete Ordinates Transport Code (TORT). These procedures produce much more accuracy in theflux solutions for a given mesh size, or allow a smaller mesh to be used in order to reduce costs. The first method is a special adaptation of the linear nodal method proposed by Walters and O`Dell. The basic method has been extensively adapted in order to avoid numerical distortions that may occur in shielding problems. The second method is a characteristic procedure with linear expansion of sources and boundary flows. These methods are in widespread use in the TORT code.

  16. Evaluation of a Stirling engine heater bypass with the NASA Lewis nodal-analysis performance code

    SciTech Connect

    Sullivan, T.J.

    1986-05-01

    In support of the US Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Research Center investigated whether bypassing the P-40 Stirling engine heater during regenerative cooling would improve the engine thermal efficiency. The investigation was accomplished by using the Lewis nodal-analysis Stirling engine computer model. Bypassing the P-40 Stirling engine heater at full power resulted in a rise in the indicated thermal efficiency from 40.6 to 41.0 percent. For the idealized (some losses not included) heater bypass that was analyzed, this benefit is not considered significant.

  17. Treatment of paroxysmal nodal tachycardia by dual demand pacemaker in the coronary sinus.

    PubMed Central

    O'Keeffe, D B; Curry, P V; Sowton, E

    1981-01-01

    A patient with refractory paroxysmal atrioventricular nodal re-entrant tachycardia had required direct current cardioversion to terminate attacks on 83 occasions. A dual demand pacemaker was implanted to sense and interrupt attacks of tachycardia automatically. The pacing electrode was positioned in the proximal coronary sinus near to the atrioventricular node; a site from which fixed rate underdrive pacing successfully interrupted attacks throughout a trial period of one week, with a lead left in this position on a temporary basis. Complete control of the arrhythmia was obtained in the six months after pacemaker implantation. Images PMID:7459160

  18. Light Spectral Quality Effects on the Growth of Potato (Solanum Tuberosum L.) Nodal Cutttings in Vitro

    NASA Technical Reports Server (NTRS)

    Wilson, Deborah A.; Weigel, Russell, C.; Wheeler, Raymond M.; Sager, John C.

    1993-01-01

    The effects of light spectral quality on the growth of in vitro nodal cutting of potato (Solanum tuberosum) cultivars Norland, Superior, Kennebec, and Denali were examined. The different light spectra were provided by Vita-Lite fluorescent (VF) (a white light control), blue fluorescent (BF), red fluorescent (RF), low-pressure sodium (LPS), and a combination of low-pressure sodium plus cool-white fluorescent lamp (LPS/CWF). Results suggested that shoot morphologic development of in vitro grown potato plants can be controlled by controlling irradiant spectral quality.

  19. Embryonic stem cells: protein interaction networks*

    PubMed Central

    Ng, Patricia Miang-Lon; Lufkin, Thomas

    2012-01-01

    Embryonic stem cells have the ability to differentiate into nearly all cell types. However, the molecular mechanism of its pluripotency is still unclear. Oct3/4, Sox2 and Nanog are important factors of pluripotency. Oct3/4 (hereafter referred to as Oct4), in particular, has been an irreplaceable factor in the induction of pluripotency in adult cells. Proteins interacting with Oct4 and Nanog have been identified via affinity purification and mass spectrometry. These data, together with iterative purifications of interacting proteins allowed a protein interaction network to be constructed. The network currently includes 77 transcription factors, all of which are interconnected in one network. In-depth studies of some of these transcription factors show that they all recruit the NuRD complex. Hence, transcription factor clustering and chromosomal remodeling are key mechanism used by embryonic stem cells. Studies using RNA interference suggest that more pluripotency genes are yet to be discovered via protein-protein interactions. More work is required to complete and curate the embryonic stem cell protein interaction network. Analysis of a saturated protein interaction network by system biology tools can greatly aid in the understanding of the embryonic stem cell pluripotency network. PMID:22639699

  20. Nodal promotes the self-renewal of human colon cancer stem cells via an autocrine manner through Smad2/3 signaling pathway.

    PubMed

    Gong, Yuehua; Guo, Ying; Hai, Yanan; Yang, Hao; Liu, Yang; Yang, Shi; Zhang, Zhenzhen; Ma, Meng; Liu, Linhong; Li, Zheng; He, Zuping

    2014-01-01

    Colorectal cancer is one of the most common and fatal tumors. However, molecular mechanisms underlying carcinogenesis of colorectal cancer remain largely undefined. Here, we explored the expression and function of Nodal in colon cancer stem cells (CCSCs). Nodal and its receptors were present in numerous human colorectal cancer cell lines. NODAL and ALK-4 were coexpressed in human colon cancerous tissues, and NODAL, CD24, and CD44, markers for CCSCs, were expressed at higher levels in human colon cancerous tissues than adjacent noncancerous colon tissues. Human CCSCs were isolated by magnetic activated cell sorting using anti-CD24 and anti-CD44. Nodal transcript and protein were hardly detectable in CD44- or CD24-negative human colorectal cancer cell lines, whereas Nodal and its receptors were present in CCSCs. Notably, Nodal facilitated spheroid formation of human CCSCs, and phosphorylation of Smad2 and Smad3 was activated by Nodal in cells of spheres derived from human CCSCs. Collectively, these results suggest that Nodal promotes the self-renewal of human CCSCs and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway. This study provides a novel insight into molecular mechanisms controlling fate of human CCSCs and offers new targets for gene therapy of human colorectal cancer.

  1. [Dermatoglyphics in children with embryonic tumors (author's transl)].

    PubMed

    Gutjahr, P; Wolffram, T; Emmrich, P

    1975-08-11

    Dermatoglyphics were analyzed in 60 children with embryonic tumors. In comparison with normal children, several differences were found. Thus, the embryonal origin of the different tumors is underlined and the hypothesis of embryonic tumors as malformations is sustained. These tumors seem to be the clinically most important manifestation of a much more comprehensive malformation syndrome, which is not yet known in all its details.

  2. Nodal and BMP2/4 signaling organizes the oral-aboral axis of the sea urchin embryo.

    PubMed

    Duboc, Véronique; Röttinger, Eric; Besnardeau, Lydia; Lepage, Thierry

    2004-03-01

    In the sea urchin embryo, the oral-aboral axis is specified after fertilization by mechanisms that are largely unknown. We report that early sea urchin embryos express Nodal and Antivin in the presumptive oral ectoderm and demonstrate that these genes control formation of the oral-aboral axis. Overexpression of nodal converted the whole ectoderm into oral ectoderm and induced ectopic expression of the orally expressed genes goosecoid, brachyury, BMP2/4, and antivin. Conversely, when the function of Nodal was blocked, by injection of an antisense Morpholino oligonucleotide or by injection of antivin mRNA, neither the oral nor the aboral ectoderm were specified. Injection of nodal mRNA into Nodal-deficient embryos induced an oral-aboral axis in a largely non-cell-autonomous manner. These observations suggest that the mechanisms responsible for patterning the oral-aboral axis of the sea urchin embryo may share similarities with mechanisms that pattern the dorsoventral axis of other deuterostomes.

  3. DIF3D nodal neutronics option for two- and three-dimensional diffusion theory calculations in hexagonal geometry. [LMFBR

    SciTech Connect

    Lawrence, R.D.

    1983-03-01

    A nodal method is developed for the solution of the neutron-diffusion equation in two- and three-dimensional hexagonal geometries. The nodal scheme has been incorporated as an option in the finite-difference diffusion-theory code DIF3D, and is intended for use in the analysis of current LMFBR designs. The nodal equations are derived using higher-order polynomial approximations to the spatial dependence of the flux within the hexagonal-z node. The final equations, which are cast in the form of inhomogeneous response-matrix equations for each energy group, involved spatial moments of the node-interior flux distribution plus surface-averaged partial currents across the faces of the node. These equations are solved using a conventional fission-source iteration accelerated by coarse-mesh rebalance and asymptotic source extrapolation. This report describes the mathematical development and numerical solution of the nodal equations, as well as the use of the nodal option and details concerning its programming structure. This latter information is intended to supplement the information provided in the separate documentation of the DIF3D code.

  4. T-cell leukemia 1 expression in nodal Epstein-Barr virus-negative diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.

    PubMed

    Gualco, Gabriela; Weiss, Lawrence M; Barber, Glen N; Bacchi, Carlos E

    2010-09-01

    The physiologic expression of the product of the proto-oncogene TCL1 (T-cell leukemia 1) is primarily restricted to early embryonic cells. In nonneoplastic B cells, the expression of TCL1 is determined by the differentiation step with silencing at the germinal center stage. TCL1 protein is overexpressed in a wide variety of human diseases. It has been shown that TCL1 is a powerful B-cell oncogene, which has been implicated in the pathogenesis of various types of mature B-cell lymphomas. There is no comparative information in the literature addressing the expression of TCL1 in pediatric and adult nodal diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma. We studied 55 cases of adult and pediatric diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma to analyze the phenotypic profile of these lymphomas, including TCL1 expression, and its relationship with clinical outcome in different age groups. The cases were analyzed by immunohistochemistry for the expression of TCL1, CD10, BCL-2, BCL-6, and MUM1. We also evaluated c-MYC translocation by fluorescence in situ hybridization. TCL1 was observed in 11 cases, 5 pediatric and 6 adult cases, all but one diffuse large B-cell lymphoma. Pediatric cases showed a significant association between TCL1 expression, high proliferative index, and presence of c-MYC translocation. TCL1 positivity was predominantly found in germinal center phenotype diffuse large B-cell lymphoma. Overall survival was worse in adult TCL1-positive cases than pediatric ones. Primary mediastinal large B-cell lymphomas infrequently expressed TCL1 in both age groups.

  5. D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.

    PubMed Central

    Lankford, K L; DeMello, F G; Klein, W L

    1988-01-01

    Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators. Images PMID:3380807

  6. D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.

    PubMed Central

    Lankford, K L; DeMello, F G; Klein, W L

    1988-01-01

    Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators. Images PMID:3357895

  7. The transcription factor Pitx2 positions the embryonic axis and regulates twinning.

    PubMed

    Torlopp, Angela; Khan, Mohsin A F; Oliveira, Nidia M M; Lekk, Ingrid; Soto-Jiménez, Luz Mayela; Sosinsky, Alona; Stern, Claudio D

    2014-01-01

    Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left-right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. PMID:25496870

  8. Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.

    PubMed

    Kondoh, Hisato; Takada, Shinji; Takemoto, Tatsuya

    2016-06-01

    The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism. PMID:27279156

  9. The transcription factor Pitx2 positions the embryonic axis and regulates twinning

    PubMed Central

    Torlopp, Angela; Khan, Mohsin A F; Oliveira, Nidia M M; Lekk, Ingrid; Soto-Jiménez, Luz Mayela; Sosinsky, Alona; Stern, Claudio D

    2014-01-01

    Embryonic polarity of invertebrates, amphibians and fish is specified largely by maternal determinants, which fixes cell fates early in development. In contrast, amniote embryos remain plastic and can form multiple individuals until gastrulation. How is their polarity determined? In the chick embryo, the earliest known factor is cVg1 (homologous to mammalian growth differentiation factor 1, GDF1), a transforming growth factor beta (TGFβ) signal expressed posteriorly before gastrulation. A molecular screen to find upstream regulators of cVg1 in normal embryos and in embryos manipulated to form twins now uncovers the transcription factor Pitx2 as a candidate. We show that Pitx2 is essential for axis formation, and that it acts as a direct regulator of cVg1 expression by binding to enhancers within neighbouring genes. Pitx2, Vg1/GDF1 and Nodal are also key actors in left–right asymmetry, suggesting that the same ancient polarity determination mechanism has been co-opted to different functions during evolution. DOI: http://dx.doi.org/10.7554/eLife.03743.001 PMID:25496870

  10. Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.

    PubMed

    Kondoh, Hisato; Takada, Shinji; Takemoto, Tatsuya

    2016-06-01

    The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism.

  11. Indications for Pelvic Nodal Treatment in Prostate Cancer Should Change. Validation of the Roach Formula in a Large Extended Nodal Dissection Series

    SciTech Connect

    Abdollah, Firas; Cozzarini, Cesare; Suardi, Nazareno; Gallina, Andrea; Capitanio, Umberto; Bianchi, Marco; Tutolo, Manuela; Salonia, Andrea; La Macchia, Mariangela; Di Muzio, Nadia; Rigatti, Patrizio; Montorsi, Francesco; Briganti, Alberto

    2012-06-01

    Purpose: Previous studies have criticized the predicting ability of the Roach formula in assessing the risk of lymph node invasion (LNI) in contemporary patients with prostate cancer (PCa) due to a significant overestimation of LNI rates. However, all those studies included patients treated with limited pelvic lymph node dissection (PLND), which is associated with high rates of false negative findings. We hypothesized that the Roach formula is still an accurate tool for LNI predictions if an extended PLND (ePLND) is performed. Methods and Materials: We included 3,115 consecutive patients treated with radical prostatectomy and ePLND between 2000 and 2010 at a single tertiary referral center. Extended PLND consisted of removal of obturator, external iliac, and hypogastric lymph nodes. We externally validated the Roach formula by using the area under the receiver operating characteristics curve and calibration plot method. Moreover, we tested the performance characteristics of different formula-generated cutoff values ranging from 1% to 20%. Results: The accuracy of the Roach formula was 80.3%. The calibration showed only a minor underestimation of the LNI risk in high-risk patients (6.7%). According to the Roach formula, the use of 15% cut off would have allowed 74.2% (2,311/3,115) of patients to avoid nodal irradiation, while up to 32.7% (111/336) of all patients with LNI would have been missed. When the cut off was lowered to 6%, nodal treatment would have been spared in 1,541 (49.5%) patients while missing 41 LNI patients. The sensitivity, specificity, and negative predictive values associated with the 6% cut off were 87.9%, 54%, and 97.3%, respectively. Conclusions: The Roach formula is still accurate and does not overestimate the rate of LNI in contemporary prostate cancer patients if they are treated with ePLND. However, the recommended cut off of 15% would miss approximately one-third of patients with LNI. Based on our results, the cut off should be lowered to

  12. The lunar nodal tide and the distance to tne Moon during the Precambrian era

    NASA Technical Reports Server (NTRS)

    Walker, J. C. G.; Zahnle, K. J.

    1986-01-01

    The origin and early evolution of life on Earth occurred under physical and chemical conditions distinctly different from those of the present day. The broad goal of this research program is to characterize these conditions. One aspect involves the dynamics of the Earth-Moon system, the distance of the Moon from the Earth, and the length of the day. These have evolved during the course of Earth history as a result of the dissipation of tidal energy. As the moon has receded the amplitude of oceanic tides has decreased while the increasing length of the day should have influenced climate and the circulation of atmosphere and ocean. A 23.3 year periodicity preserved in a 2500 million year old banded iron-formation was interpreted as reflecting the climatic influence of the lunar nodal tide. The corresponding lunar distance would then have been approx. 52 Earth radii. The influence of the lunar nodal tide is also apparent in rocks with an age of 680 million years B.P. The derived value for lunar distance 2500 million years ago is the only datum on the dynamics of the Earth-Moon system during the Precambrian era of Earth history. The implied development of Precambrian tidal friction is in accord with more recent paleontological evidence as well as the long term stability of the lunar orbit.

  13. New Method for Imaging Gap Nodal Structure of Unconventional Superconductors through the Anisotropic Nonlinear Meissner Effect

    NASA Astrophysics Data System (ADS)

    Bae, Seokjin; Tan, Yuewen; Gogna, Rahul; Mendelsohn, Nathan; Remillard, Steven; Anlage, Steven

    We present a new measurement method which can be used to image gap nodal structure of superconductors whose pairing symmetry is unknown. This method utilizes photoresponse from a microwave resonance of the superconducting sample perturbed by a scanned laser spot. For an epitaxial or single crystal sample, the anisotropy of this photoresponse is directly related to that of gap function via the non-linear Meissner coefficient, so the gap nodal directions can be inferred from the photoresponse image. The significant advantage of the presented method over previous spiral or lumped circuit resonator methods is that it does not require a complicated lithographic patterning process which often degrades superconductivity or introduces defect-dominant photoresponse and hence limits one from testing various kinds of materials. The validity of the method is confirmed both by HFSS simulation and experiments on unpatterned superconducting thin films. Photoresponse images from example unconventional superconductors will be also presented and discussed. This work is supported by the NSF Grants DMR-1410712.

  14. Advanced computational methods for nodal diffusion, Monte Carlo, and S(sub N) problems

    NASA Astrophysics Data System (ADS)

    Martin, W. R.

    1993-01-01

    This document describes progress on five efforts for improving effectiveness of computational methods for particle diffusion and transport problems in nuclear engineering: (1) Multigrid methods for obtaining rapidly converging solutions of nodal diffusion problems. An alternative line relaxation scheme is being implemented into a nodal diffusion code. Simplified P2 has been implemented into this code. (2) Local Exponential Transform method for variance reduction in Monte Carlo neutron transport calculations. This work yielded predictions for both 1-D and 2-D x-y geometry better than conventional Monte Carlo with splitting and Russian Roulette. (3) Asymptotic Diffusion Synthetic Acceleration methods for obtaining accurate, rapidly converging solutions of multidimensional SN problems. New transport differencing schemes have been obtained that allow solution by the conjugate gradient method, and the convergence of this approach is rapid. (4) Quasidiffusion (QD) methods for obtaining accurate, rapidly converging solutions of multidimensional SN Problems on irregular spatial grids. A symmetrized QD method has been developed in a form that results in a system of two self-adjoint equations that are readily discretized and efficiently solved. (5) Response history method for speeding up the Monte Carlo calculation of electron transport problems. This method was implemented into the MCNP Monte Carlo code. In addition, we have developed and implemented a parallel time-dependent Monte Carlo code on two massively parallel processors.

  15. Advanced computational methods for nodal diffusion, Monte Carlo, and S[sub N] problems

    SciTech Connect

    Martin, W.R.

    1993-01-01

    This document describes progress on five efforts for improving effectiveness of computational methods for particle diffusion and transport problems in nuclear engineering: (1) Multigrid methods for obtaining rapidly converging solutions of nodal diffusion problems. A alternative line relaxation scheme is being implemented into a nodal diffusion code. Simplified P2 has been implemented into this code. (2) Local Exponential Transform method for variance reduction in Monte Carlo neutron transport calculations. This work yielded predictions for both 1-D and 2-D x-y geometry better than conventional Monte Carlo with splitting and Russian Roulette. (3) Asymptotic Diffusion Synthetic Acceleration methods for obtaining accurate, rapidly converging solutions of multidimensional SN problems. New transport differencing schemes have been obtained that allow solution by the conjugate gradient method, and the convergence of this approach is rapid. (4) Quasidiffusion (QD) methods for obtaining accurate, rapidly converging solutions of multidimensional SN Problems on irregular spatial grids. A symmetrized QD method has been developed in a form that results in a system of two self-adjoint equations that are readily discretized and efficiently solved. (5) Response history method for speeding up the Monte Carlo calculation of electron transport problems. This method was implemented into the MCNP Monte Carlo code. In addition, we have developed and implemented a parallel time-dependent Monte Carlo code on two massively parallel processors.

  16. Oyster Creek cycle 10 nodal model parameter optimization study using PSMS

    SciTech Connect

    Dougher, J.D.

    1987-01-01

    The power shape monitoring system (PSMS) is an on-line core monitoring system that uses a three-dimensional nodal code (NODE-B) to perform nodal power calculations and compute thermal margins. The PSMS contains a parameter optimization function that improves the ability of NODE-B to accurately monitor core power distributions. This functions iterates on the model normalization parameters (albedos and mixing factors) to obtain the best agreement between predicted and measured traversing in-core probe (TIP) reading on a statepoint-by-statepoint basis. Following several statepoint optimization runs, an average set of optimized normalization parameters can be determined and can be implemented into the current or subsequent cycle core model for on-line core monitoring. A statistical analysis of 19 high-power steady-state state-points throughout Oyster Creek cycle 10 operation has shown a consistently poor virgin model performance. The normalization parameters used in the cycle 10 NODE-B model were based on a cycle 8 study, which evaluated only Exxon fuel types. The introduction of General Electric (GE) fuel into cycle 10 (172 assemblies) was a significant fuel/core design change that could have altered the optimum set of normalization parameters. Based on the need to evaluate a potential change in the model normalization parameters for cycle 11 and in an attempt to account for the poor cycle 10 model performance, a parameter optimization study was performed.

  17. Hybrid modal nodal method for multibody smart structure model reduction: application to modal feedback control

    NASA Astrophysics Data System (ADS)

    Matichard, Fabrice; Gaudiller, Luc

    2006-12-01

    The hybrid modal nodal (HMN) method, designed for multibody smart structure model reduction and feedback control development, is based on the independent modeling of structural and electromechanical behavior. Firstly, this approach permits reducing the model of substructures independently of the electromechanical behavior. This allows choosing the most adapted component mode synthesis (CMS) method and corresponding code for any application, something that is not permitted by classical multi-physics projection-based methods. Thus, the substructuring process used in this paper is based on super-elements directly adapted for multibody dynamics modeling. Secondly, the electromechanical behavior of distributed components is introduced into the structural modal model via a nodal formulation. Its independence of any projection guarantees accuracy and its formulation is valid whatever the multibody assembly and its modal shapes. The proposed application is composed of successive developments and experiments designed to validate the model reduction method, its implementation and its use for modal feedback control, i.e. a smart beam, actively controlled by piezoelectric ceramics. It is successively clamped to illustrate the electromechanical coupling reduction, articulated to introduce the rigid-body/flexible mode coupling reduction and, finally, bi-articulated in order to deal with the nonlinear problem.

  18. Cooperative Wnt-Nodal Signals Regulate the Patterning of Anterior Neuroectoderm

    PubMed Central

    Yaguchi, Junko; Takeda, Noriyo; Inaba, Kazuo; Yaguchi, Shunsuke

    2016-01-01

    When early canonical Wnt is experimentally inhibited, sea urchin embryos embody the concept of a Default Model in vivo because most of the ectodermal cell fates are specified as anterior neuroectoderm. Using this model, we describe here how the combination of orthogonally functioning anteroposterior Wnt and dorsoventral Nodal signals and their targeting transcription factors, FoxQ2 and Homeobrain, regulates the precise patterning of normal neuroectoderm, of which serotonergic neurons are differentiated only at the dorsal/lateral edge. Loss-of-function experiments revealed that ventral Nodal is required for suppressing the serotonergic neural fate in the ventral side of the neuroectoderm through the maintenance of foxQ2 and the repression of homeobrain expression. In addition, non-canonical Wnt suppressed homeobrain in the anterior end of the neuroectoderm, where serotonergic neurons are not differentiated. Canonical Wnt, however, suppresses foxQ2 to promote neural differentiation. Therefore, the three-dimensionally complex patterning of the neuroectoderm is created by cooperative signals, which are essential for the formation of primary and secondary body axes during embryogenesis. PMID:27101101

  19. Comparison of Nodal Risk Formula and MR Lymphography for Predicting Lymph Node Involvement in Prostate Cancer

    SciTech Connect

    Deserno, Willem M.L.L.G.; Debats, Oscar A.; Rozema, Tom; Fortuin, Ansje S.; Heesakkers, Roel A.M.; Hoogeveen, Yvonne; Peer, Petronella G.M.; Barentsz, Jelle O.; Lin, Emile N.J.T. van

    2011-09-01

    Purpose: To compare the nodal risk formula (NRF) as a predictor for lymph node (LN) metastasis in patients with prostate cancer with magnetic resonance lymphography (MRL) using Ultrasmall Super-Paramagnetic particles of Iron Oxide (USPIO) and with histology as gold standard. Methods and Materials: Logistic regression analysis was performed with the results of histopathological evaluation of the LN as dependent variable and the nodal risk according to the NRF and the result of MRL as independent input variables. Receiver operating characteristic (ROC) analysis was performed to assess the performance of the models. Results: The analysis included 375 patients. In the single-predictor regression models, the NRF and MRL results were both significantly (p <0.001) predictive of the presence of LN metastasis. In the models with both predictors included, NRF was nonsignificant (p = 0.126), but MRL remained significant (p <0.001). For NRF, sensitivity was 0.79 and specificity was 0.38; for MRL, sensitivity was 0.82 and specificity was 0.93. After a negative MRL result, the probability of LN metastasis is 4% regardless of the NRF result. After a positive MRL, the probability of having LN metastasis is 68%. Conclusions: MRL is a better predictor of the presence of LN metastasis than NRF. Using only the NRF can lead to a significant overtreatment on the pelvic LN by radiation therapy. When the MRL result is available, the NRF is no longer of added value.

  20. Inland waterway ports nodal attraction indices relevant in development strategies on regional level

    NASA Astrophysics Data System (ADS)

    Dinu, O.; Burciu, Ş.; Oprea, C.; Ilie, A.; Rosca, M.

    2016-08-01

    Present paper aims to propose a set of ranking indices and related criteria, concerning mainly spatial analysis, for the inland waterway port, with special view on inland ports of Danube. Commonly, the attraction potential of a certain transport node is assessed by its spatial accessibility indices considering both spatial features of the location provided by the networks that connect into that node and its economic potential defining the level of traffic flows depending on the economic centers of its hinterland. Paper starts with a overview of the critical needs that are required for potential sites to become inland waterway ports and presents nodal functions that coexist at different levels, leading to a port hierarchy from the points of view of: capacity, connection to hinterland, traffic structure and volume. After a brief review of the key inland waterway port ranking criterion, a selection of nodal attraction measures is made. Particular considerations for the Danube inland port case follows proposed methodology concerning indices of performance for network scale and centrality. As expected, the shorter the distance from an inland port to the nearest access point the greater accessibility. Major differences in ranking, dependent on selected criterion, were registered.

  1. [Successful selective electrical ablation of the retrograde pathway in atrioventricular nodal reentry tachycardia associated with syncope].

    PubMed

    Lukl, J; Cíhalík, C

    1992-01-01

    A 55-year-old man was admitted to the intensive care unit on account of repeatedly occurring syncopes which developed at the peak of physical exertion. The attack was reproduced by exercise on a bicycle ergometer: the patient developed paroxysmal tachycardia with a narrow QRS and a frequency of 160/min leading after 20 sec. to severe hypotension and loss of consciousness. The same tachycardia caused by programmed atrial stimulation caused a drop of tension in the recumbent position by 30 mmHg and after more detailed analysis during electrophysiological examination it was evaluated as atrioventricular nodal reentrant tachycardia. By an electric discharge of 300 J administered by means of a stimulation electrode 7F USCI into the area of the AV node the retrograde conduction through the perinodal rapid pathways was completely interrupted and 1st. degree atrioventricular block developed. Repeated electrophysiological examination and exercise tests on a bicycle ergometer provided evidence of the disappearance of the retrograde pathway and the impossibility to elicit AVNRT. The authors express the view that the rapid perinodal pathway is interrupted in successful cases in both directions and the 1st. degree AV block is due to conduction along a slow pathway and not incidental slowing of conduction along the rapid pathway which is the generally accepted interpretation. Modification of the atrioventricular conduction by interruption of the rapid pathway by fulguration is according to data in the literature and the described patient a method which makes is possible to cure severe atrioventricular nodal reentrant tachycardias.

  2. Nodal marginal zone B cells in mice: a novel subset with dormant self-reactivity

    PubMed Central

    Palm, Anna-Karin E.; Friedrich, Heike C.; Kleinau, Sandra

    2016-01-01

    Marginal zone (MZ) B cells, representing a distinct subset of innate-like B cells, mount rapid T-independent responses to blood-borne antigens. They express low-affinity polyreactive antigen receptors that recognize both foreign and self-structures. The spleen is considered the exclusive site for murine MZ B cells. However, we have here identified B cells with a MZ B-cell phenotype in the subcapsular sinuses of mouse lymph nodes. The nodal MZ (nMZ) B cells display high levels of IgM, costimulators and TLRs, and are represented by naïve and memory cells. The frequency of nMZ B cells is about 1–6% of nodal B cells depending on mouse strain, with higher numbers in older mice and a trend of increased numbers in females. There is a significant expansion of nMZ B cells following immunization with an autoantigen, but not after likewise immunization with a control protein or with the adjuvant alone. The nMZ B cells secrete autoantibodies upon activation and can efficiently present autoantigen to cognate T cells in vitro, inducing T-cell proliferation. The existence of self-reactive MZ B cells in lymph nodes may be a source of autoantigen-presenting cells that in an unfortunate environment may activate T cells leading to autoimmunity. PMID:27277419

  3. Cooperative Wnt-Nodal Signals Regulate the Patterning of Anterior Neuroectoderm.

    PubMed

    Yaguchi, Junko; Takeda, Noriyo; Inaba, Kazuo; Yaguchi, Shunsuke

    2016-04-01

    When early canonical Wnt is experimentally inhibited, sea urchin embryos embody the concept of a Default Model in vivo because most of the ectodermal cell fates are specified as anterior neuroectoderm. Using this model, we describe here how the combination of orthogonally functioning anteroposterior Wnt and dorsoventral Nodal signals and their targeting transcription factors, FoxQ2 and Homeobrain, regulates the precise patterning of normal neuroectoderm, of which serotonergic neurons are differentiated only at the dorsal/lateral edge. Loss-of-function experiments revealed that ventral Nodal is required for suppressing the serotonergic neural fate in the ventral side of the neuroectoderm through the maintenance of foxQ2 and the repression of homeobrain expression. In addition, non-canonical Wnt suppressed homeobrain in the anterior end of the neuroectoderm, where serotonergic neurons are not differentiated. Canonical Wnt, however, suppresses foxQ2 to promote neural differentiation. Therefore, the three-dimensionally complex patterning of the neuroectoderm is created by cooperative signals, which are essential for the formation of primary and secondary body axes during embryogenesis. PMID:27101101

  4. Observation of topological nodal fermion semimetal phase in ZrSiS

    NASA Astrophysics Data System (ADS)

    Neupane, Madhab; Belopolski, Ilya; Hosen, M. Mofazzel; Sanchez, Daniel S.; Sankar, Raman; Szlawska, Maria; Xu, Su-Yang; Dimitri, Klauss; Dhakal, Nagendra; Maldonado, Pablo; Oppeneer, Peter M.; Kaczorowski, Dariusz; Chou, Fangcheng; Hasan, M. Zahid; Durakiewicz, Tomasz

    2016-05-01

    Unveiling new topological phases of matter is one of the current objectives in condensed matter physics. Recent experimental discoveries of Dirac and Weyl semimetals prompt the search for other exotic phases of matter. Here we present a systematic angle-resolved photoemission spectroscopy study of ZrSiS, a prime topological nodal semimetal candidate. Our wider Brillouin zone (BZ) mapping shows multiple Fermi surface pockets such as the diamond-shaped Fermi surface, elliptical-shaped Fermi surface, and a small electron pocket encircling at the zone center (Γ ) point, the M point, and the X point of the BZ, respectively. We experimentally establish the spinless nodal fermion semimetal phase in ZrSiS, which is supported by our first-principles calculations. Our findings evidence that the ZrSiS-type of material family is a new platform on which to explore exotic states of quantum matter; these materials are expected to provide an avenue for engineering two-dimensional topological insulator systems.

  5. Nodal predictive error model and Bayesian approach for thermal diffusivity and heat source mapping

    NASA Astrophysics Data System (ADS)

    Massard, H.; Fudym, Olivier; Orlande, H. R. B.; Batsale, J. C.

    2010-07-01

    This article aims at solving a two-dimensional inverse heat conduction problem in order to retrieve both the thermal diffusivity and heat source field in a thin plate. A spatial random heat pulse is applied to the plate and the thermal response is analysed. The inverse approach is based on the minimisation of a nodal predictive error model, which yields a linear estimation problem. As a result of this approach, the sensitivity matrix is directly filled with experimental data, and thus is partially noisy. Bayesian estimators, such as the Maximum A Posteriori and a Markov Chain Monte Carlo approach (Metropolis-Hastings), are implemented and compared with the Ordinary Least Squares solution. Simulated temperature measurements are used in the inverse analysis. The nodal strategy relies on the availability of temperature measurements with fine spatial resolution and high frequency, typical of nowadays infrared cameras. The effects of both the measurement errors and of the model errors on the inverse problem solution are also analysed.

  6. Nodal bilayer-splitting controlled by spin-orbit interactions in underdoped high-Tc cuprates

    DOE PAGESBeta

    Harrison, N.; Ramshaw, B. J.; Shekhter, A.

    2015-06-03

    The highest superconducting transition temperatures in the cuprates are achieved in bilayer and trilayer systems, highlighting the importance of interlayer interactions for high Tc. It has been argued that interlayer hybridization vanishes along the nodal directions by way of a specific pattern of orbital overlap. Recent quantum oscillation measurements in bilayer cuprates have provided evidence for a residual bilayer-splitting at the nodes that is sufficiently small to enable magnetic breakdown tunneling at the nodes. Here we show that several key features of the experimental data can be understood in terms of weak spin-orbit interactions naturally present in bilayer systems, whosemore » primary effect is to cause the magnetic breakdown to be accompanied by a spin flip. These features can now be understood to include the equidistant set of three quantum oscillation frequencies, the asymmetry of the quantum oscillation amplitudes in c-axis transport compared to ab-plane transport, and the anomalous magnetic field angle dependence of the amplitude of the side frequencies suggestive of small effective g-factors. We suggest that spin-orbit interactions in bilayer systems can further affect the structure of the nodal quasiparticle spectrum in the superconducting phase. PACS numbers: 71.45.Lr, 71.20.Ps, 71.18.+y« less

  7. Conservation defines functional motifs in the squint/nodal-related 1 RNA dorsal localization element

    PubMed Central

    Gilligan, Patrick C.; Kumari, Pooja; Lim, Shimin; Cheong, Albert; Chang, Alex; Sampath, Karuna

    2011-01-01

    RNA localization is emerging as a general principle of sub-cellular protein localization and cellular organization. However, the sequence and structural requirements in many RNA localization elements remain poorly understood. Whereas transcription factor-binding sites in DNA can be recognized as short degenerate motifs, and consensus binding sites readily inferred, protein-binding sites in RNA often contain structural features, and can be difficult to infer. We previously showed that zebrafish squint/nodal-related 1 (sqt/ndr1) RNA localizes to the future dorsal side of the embryo. Interestingly, mammalian nodal RNA can also localize to dorsal when injected into zebrafish embryos, suggesting that the sequence motif(s) may be conserved, even though the fish and mammal UTRs cannot be aligned. To define potential sequence and structural features, we obtained ndr1 3′-UTR sequences from approximately 50 fishes that are closely, or distantly, related to zebrafish, for high-resolution phylogenetic footprinting. We identify conserved sequence and structural motifs within the zebrafish/carp family and catfish. We find that two novel motifs, a single-stranded AGCAC motif and a small stem-loop, are required for efficient sqt RNA localization. These findings show that comparative sequencing in the zebrafish/carp family is an efficient approach for identifying weak consensus binding sites for RNA regulatory proteins. PMID:21149265

  8. Misalignment-induced nodal aberration fields in two-mirror astronomical telescopes.

    PubMed

    Schmid, Tobias; Thompson, Kevin P; Rolland, Jannick P

    2010-06-01

    We present the effects of misalignments on the field dependence of the third-order aberration fields of traditional, two-mirror astronomical telescopes in the context of nodal aberration theory, which we believe is the most general and extensible framework for describing and improving on-station performance. While many of the advantages of nodal aberration theory, compared to other, often power series expansion-based descriptions of misalignment effects on aberrations, become particularly important when analyzing telescopes with more than two mirrors, or in the presence of figure errors; this paper aims to provide and demonstrate the fundamental concepts needed to fully describe the state of correction of misaligned two-mirror telescopes. Importantly, it is shown that the assumption that perfect performance on axis ensures a fully aligned telescope is false, and we demonstrate that if Ritchey-Chrétien telescopes are aligned for zero coma on axis as the sole criterion, formidable misalignments will likely remain, leading to image quality degradation, particularly beyond midfield caused by astigmatism with binodal field dependence (i.e., astigmatism goes to zero at two points in the field).

  9. Reflector modelling of small high leakage cores making use of multi-group nodal equivalence theory

    SciTech Connect

    Theron, S. A.; Reitsma, F.

    2012-07-01

    This research focuses on modelling reflectors in typical material testing reactors (MTRs). Equivalence theory is used to homogenise and collapse detailed transport solutions to generate equivalent nodal parameters and albedo boundary conditions for reflectors, for subsequent use in full core nodal diffusion codes. This approach to reflector modelling has been shown to be accurate for two-group large commercial light water reactor (LWR) analysis, but has not been investigated for MTRs. MTRs are smaller, with much larger leakage, environment sensitivity and multi-group spectrum dependencies than LWRs. This study aims to determine if this approach to reflector modelling is an accurate and plausible homogenisation technique for the modelling of small MTR cores. The successful implementation will result in simplified core models, better accuracy and improved efficiency of computer simulations. Codes used in this study include SCALE 6.1, OSCAR-4 and EQUIVA (the last two codes are developed and used at Necsa). The results show a five times reduction in calculational time for the proposed reduced reactor model compared to the traditional explicit model. The calculated equivalent parameters however show some sensitivity to the environment used to generate them. Differences in the results compared to the current explicit model, require more careful investigation including comparisons with a reference result, before its implementation can be recommended. (authors)

  10. Universal heat conduction in Ce1 -xYbxCoIn5 : Evidence for robust nodal d -wave superconducting gap

    NASA Astrophysics Data System (ADS)

    Xu, Y.; Dong, J. K.; Lum, I. K.; Zhang, J.; Hong, X. C.; He, L. P.; Wang, K. F.; Ma, Y. C.; Petrovic, C.; Maple, M. B.; Shu, L.; Li, S. Y.

    2016-02-01

    In the heavy-fermion superconductor Ce1 -xYbxCoIn5 , Yb doping was reported to cause a possible change from nodal d -wave superconductivity to a fully gapped d -wave molecular superfluid of composite pairs near x ≈0.07 (nominal value xnom=0.2 ). Here we present systematic thermal conductivity measurements on Ce1 -xYbxCoIn5 (x =0.013 , 0.084, and 0.163) single crystals. The observed finite residual linear term κ0/T is insensitive to Yb doping, verifying the universal heat conduction of the nodal d -wave superconducting gap in Ce1 -xYbxCoIn5 . Similar universal heat conduction is also observed in the CeCo (In1 -yCdy )5 system. These results reveal a robust nodal d -wave gap in CeCoIn5 upon Yb or Cd doping.

  11. Shifting nodal-plane suppressions in high-order-harmonic spectra from diatomic molecules in orthogonally polarized driving fields

    NASA Astrophysics Data System (ADS)

    Das, T.; Figueira de Morisson Faria, C.

    2016-08-01

    We analyze the imprint of nodal planes in high-order-harmonic spectra from aligned diatomic molecules in intense laser fields whose components exhibit orthogonal polarizations. We show that the typical suppression in the spectra associated to nodal planes is distorted, and that this distortion can be employed to map the electron's angle of return to its parent ion. This investigation is performed semianalytically at the single-molecule response and single-active orbital level, using the strong-field approximation and the steepest descent method. We show that the velocity form of the dipole operator is superior to the length form in providing information about this distortion. However, both forms introduce artifacts that are absent in the actual momentum-space wave function. Furthermore, elliptically polarized fields lead to larger distortions in comparison to two-color orthogonally polarized fields. These features are investigated in detail for O2, whose highest occupied molecular orbital provides two orthogonal nodal planes.

  12. Spin-orbit interaction driven collective electron-hole excitations in a noncentrosymmetric nodal loop Weyl semimetal

    NASA Astrophysics Data System (ADS)

    Ahn, Kyo-Hoon; Lee, Kwan-Woo; Pickett, Warren E.

    2015-09-01

    NbP is one member of a new class of nodal loop semimetals characterized by the cooperative effects of spin-orbit coupling (SOC) and a lack of inversion center. Here transport and spectroscopic properties of NbP are evaluated using density functional theory methods. SOC together with the lack of inversion symmetry splits degeneracies, giving rise to "Russian doll nested" Fermi surfaces containing 4 ×10-4 electron (hole) carriers/f.u. Due to the modest SOC strength in Nb, the Fermi surfaces map out the Weyl nodal loops. Calculated structure around T*≈100 K in transport properties reproduces well the observed transport behavior only when SOC is included, attesting to the precision of the (delicate) calculations and the stoichiometry of the samples. Low-energy collective electron-hole excitations (plasmons) in the 20-60 meV range result from the nodal loop splitting.

  13. Atlas-Based Segmentation Improves Consistency and Decreases Time Required for Contouring Postoperative Endometrial Cancer Nodal Volumes

    SciTech Connect

    Young, Amy V.; Wortham, Angela; Wernick, Iddo; Evans, Andrew; Ennis, Ronald D.

    2011-03-01

    Purpose: Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized that atlas-based segmentation ('autocontouring') would lead to time savings and more consistent contours among physicians. Methods and Materials: A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical target volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient. Results: For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean {+-} standard deviation of 32 {+-} 9 vs. 23 {+-} 7 minutes, respectively (p = .000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30 {+-} 3 vs. 21 {+-} 5 min (p = .003), 39 {+-} 12 vs. 30 {+-} 5 min (p = .055), and 29 {+-} 5 vs. 20 {+-} 5 min (p = .0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p = .038). Conclusion: The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the target

  14. Performance of a recoverable tug for planetary missions including use of perigee propulsion and corrections for nodal regression

    NASA Technical Reports Server (NTRS)

    Borsody, J.

    1976-01-01

    Mathematical equations are derived by using the Maximum Principle to obtain the maximum payload capability of a reusable tug for planetary missions. The mathematical formulation includes correction for nodal precession of the space shuttle orbit. The tug performs this nodal correction in returning to this precessed orbit. The sample case analyzed represents an inner planet mission as defined by the declination (fixed) and right ascension of the outgoing asymptote and the mission energy. Payload capability is derived for a typical cryogenic tug and the sample case with and without perigee propulsion. Optimal trajectory profiles and some important orbital elements are also discussed.

  15. Phase I Trial of Pelvic Nodal Dose Escalation With Hypofractionated IMRT for High-Risk Prostate Cancer

    SciTech Connect

    Adkison, Jarrod B.; McHaffie, Derek R.; Bentzen, Soren M.; Patel, Rakesh R.; Khuntia, Deepak; Petereit, Daniel G.; Hong, Theodore S.; Tome, Wolfgang; Ritter, Mark A.

    2012-01-01

    Purpose: Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5 Vulgar-Fraction-One-Half weeks. Methods and Materials: Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. Results: The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving {>=}30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 {+-} 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. Conclusions: Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose

  16. An analytical discrete ordinates solution for a nodal model of a two-dimensional neutron transport problem

    SciTech Connect

    Filho, J. F. P.

    2013-07-01

    In this work, an analytical discrete ordinates method is used to solve a nodal formulation of a neutron transport problem in x, y-geometry. The proposed approach leads to an important reduction in the order of the associated eigenvalue systems, when combined with the classical level symmetric quadrature scheme. Auxiliary equations are proposed, as usually required for nodal methods, to express the unknown fluxes at the boundary introduced as additional unknowns in the integrated equations. Numerical results, for the problem defined by a two-dimensional region with a spatially constant and isotropically emitting source, are presented and compared with those available in the literature. (authors)

  17. Nodal Gap” induced by the incommensurate diagonal spin density modulation in underdoped high- Tc superconductors

    DOE PAGESBeta

    Zhou, Tao; Gao, Yi; Zhu, Jian -Xin

    2015-03-07

    Recenmore » tly it was revealed that the whole Fermi surface is fully gapped for several families of underdoped cuprates. The existence of the finite energy gap along the d-wave nodal lines (nodal gap) contrasts the common understanding of the d-wave pairing symmetry, which challenges the present theories for the high-Tcsuperconductors. Here we propose that the incommensurate diagonal spin-density-wave order can account for the above experimental observation. The Fermi surface and the local density of states are also studied. Our results are in good agreement with many important experiments in high-Tcsuperconductors.« less

  18. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.

    PubMed

    Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette; Haynes, Carol S; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B; Diaz-Sanchez, David; Cascio, Wayne E; Lynn Miranda, Marie; Gregory, Simon G; Shah, Svati H; Kraus, William E; Hauser, Elizabeth R

    2016-01-01

    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic ("traffic exposure")-a recognized vascular disease risk factor-on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3' untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family

  19. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease.

    PubMed

    Ward-Caviness, Cavin K; Neas, Lucas M; Blach, Colette; Haynes, Carol S; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B; Diaz-Sanchez, David; Cascio, Wayne E; Lynn Miranda, Marie; Gregory, Simon G; Shah, Svati H; Kraus, William E; Hauser, Elizabeth R

    2016-01-01

    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic ("traffic exposure")-a recognized vascular disease risk factor-on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3' untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene family

  20. Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-β/bone morphogenic protein signalling

    PubMed Central

    Hopwood, Blair; Tsykin, Anna; Findlay, David M; Fazzalari, Nicola L

    2007-01-01

    Osteoarthritis (OA) is characterized by alterations to subchondral bone as well as articular cartilage. Changes to bone in OA have also been identified at sites distal to the affected joint, which include increased bone volume fraction and reduced bone mineralization. Altered bone remodelling has been proposed to underlie these bone changes in OA. To investigate the molecular basis for these changes, we performed microarray gene expression profiling of bone obtained at autopsy from individuals with no evidence of joint disease (control) and from individuals undergoing joint replacement surgery for either degenerative hip OA, or fractured neck of femur (osteoporosis [OP]). The OP sample set was included because an inverse association, with respect to bone density, has been observed between OA and the low bone density disease OP. Compugen human 19K-oligo microarray slides were used to compare the gene expression profiles of OA, control and OP bone samples. Four sets of samples were analyzed, comprising 10 OA-control female, 10 OA-control male, 10 OA-OP female and 9 OP-control female sample pairs. Print tip Lowess normalization and Bayesian statistical analyses were carried out using linear models for microarray analysis, which identified 150 differentially expressed genes in OA bone with t scores above 4. Twenty-five of these genes were then confirmed to be differentially expressed (P < 0.01) by real-time PCR analysis. A substantial number of the top-ranking differentially expressed genes identified in OA bone are known to play roles in osteoblasts, osteocytes and osteoclasts. Many of these genes are targets of either the WNT (wingless MMTV integration) signalling pathway (TWIST1, IBSP, S100A4, MMP25, RUNX2 and CD14) or the transforming growth factor (TGF)-β/bone morphogenic protein (BMP) signalling pathway (ADAMTS4, ADM, MEPE, GADD45B, COL4A1 and FST). Other differentially expressed genes included WNT (WNT5B, NHERF1, CTNNB1 and PTEN) and TGF-β/BMP (TGFB1, SMAD3

  1. Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

    PubMed Central

    Ward-Caviness, Cavin K.; Neas, Lucas M.; Blach, Colette; Haynes, Carol S.; LaRocque-Abramson, Karen; Grass, Elizabeth; Dowdy, Elaine; Devlin, Robert B.; Diaz-Sanchez, David; Cascio, Wayne E.; Lynn Miranda, Marie; Gregory, Simon G.; Shah, Svati H.; Kraus, William E.; Hauser, Elizabeth R.

    2016-01-01

    There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been rarely performed particularly in the case of air pollution exposures. We performed race-stratified genome-wide gene-environment interaction association studies on European-American (EA, N = 1623) and African-American (AA, N = 554) cohorts to investigate the joint influence of common single nucleotide polymorphisms (SNPs) and residential exposure to traffic (“traffic exposure”)—a recognized vascular disease risk factor—on peripheral arterial disease (PAD). Traffic exposure was estimated via the distance from the primary residence to the nearest major roadway, defined as the nearest limited access highways or major arterial. The rs755249-traffic exposure interaction was associated with PAD at a genome-wide significant level (P = 2.29x10-8) in European-Americans. Rs755249 is located in the 3’ untranslated region of BMP8A, a member of the bone morphogenic protein (BMP) gene family. Further investigation revealed several variants in BMP genes associated with PAD via an interaction with traffic exposure in both the EA and AA cohorts; this included interactions with non-synonymous variants in BMP2, which is regulated by air pollution exposure. The BMP family of genes is linked to vascular growth and calcification and is a novel gene family for the study of PAD pathophysiology. Further investigation of BMP8A using the Genotype Tissue Expression Database revealed multiple variants with nominally significant (P < 0.05) interaction P-values in our EA cohort were significant BMP8A eQTLs in tissue types highlight relevant for PAD such as rs755249 (tibial nerve, eQTL P = 3.6x10-6) and rs1180341 (tibial artery, eQTL P = 5.3x10-6). Together these results reveal a novel gene, and possibly gene

  2. Spatiotemporal recapitulation of central nervous system development by murine embryonic stem cell-derived neural stem/progenitor cells.

    PubMed

    Okada, Yohei; Matsumoto, Arifumi; Shimazaki, Takuya; Enoki, Ryosuke; Koizumi, Amane; Ishii, Seiji; Itoyama, Yasuto; Sobue, Gen; Okano, Hideyuki

    2008-12-01

    Neural stem/progenitor cells (NS/PCs) can generate a wide variety of neural cells. However, their fates are generally restricted, depending on the time and location of NS/PC origin. Here we demonstrate that we can recapitulate the spatiotemporal regulation of central nervous system (CNS) development in vitro by using a neurosphere-based culture system of embryonic stem (ES) cell-derived NS/PCs. This ES cell-derived neurosphere system enables the efficient derivation of highly neurogenic fibroblast growth factor-responsive NS/PCs with early temporal identities and high cell-fate plasticity. Over repeated passages, these NS/PCs exhibit temporal progression, becoming epidermal growth factor-responsive gliogenic NS/PCs with late temporal identities; this change is accompanied by an alteration in the epigenetic status of the glial fibrillary acidic protein promoter, similar to that observed in the developing brain. Moreover, the rostrocaudal and dorsoventral spatial identities of the NS/PCs can be successfully regulated by sequential administration of several morphogens. These NS/PCs can differentiate into early-born projection neurons, including cholinergic, catecholaminergic, serotonergic, and motor neurons, that exhibit action potentials in vitro. Finally, these NS/PCs differentiate into neurons that form synaptic contacts with host neurons after their transplantation into wild-type and disease model animals. Thus, this culture system can be used to obtain specific neurons from ES cells, is a simple and powerful tool for investigating the underlying mechanisms of CNS development, and is applicable to regenerative treatment for neurological disorders. PMID:18757299

  3. Affinity of the heparin binding motif of Noggin1 to heparan sulfate and its visualization in the embryonic tissues.

    PubMed

    Nesterenko, Alexey M; Orlov, Eugeny E; Ermakova, Galina V; Ivanov, Igor A; Semenyuk, Pavel I; Orlov, Victor N; Martynova, Natalia Y; Zaraisky, Andrey G

    Heparin binding motifs were found in many secreted proteins and it was suggested that they are responsible for retardation of the protein diffusion within the intercellular space due to the binding to heparan sulfate proteoglycanes (HSPG). Here we used synthetic FITC labeled heparin binding motif (HBM peptide) of the Xenopus laevis secreted BMP inhibitor Noggin1 to study its diffusion along the surface of the heparin beads by FRAP method. As a result, we have found out that diffusivity of HBM-labeled FITC was indeed much lesser than those predicted by theoretical calculations even for whole protein of the Noggin size. We also compared by isothermal titration calorimetry the binding affinity of HBM and the control oligolysine peptide to several natural polyanions including heparan sulfate (HS), heparin, the bacterial dextran sulfate and salmon sperm DNA, and demonstrated that HBM significantly exceeds oligolysine peptide in the affinity to HS, heparin and DNA. By contrast, oligolysine peptide bound with higher affinity to dextran sulfate. We speculate that such a difference may ensure specificity of the morphogen binding to HSPG and could be explained by steric constrains imposed by different distribution of the negative charges along a given polymeric molecule. Finally, by using EGFP-HBM recombinant protein we have visualized the natural pattern of the Noggin1 binding sites within the X. laevis gastrula and demonstrated that these sites forms a dorsal-ventral concentration gradient, with a maximum in the dorsal blastopore lip. In sum, our data provide a quantitative basis for modeling the process of Noggin1 diffusion in embryonic tissues, considering its interaction with HSPG.

  4. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  5. Programming embryonic stem cells to neuronal subtypes

    PubMed Central

    Peljto, Mirza; Wichterle, Hynek

    2010-01-01

    Richness of neural circuits and specificity of neuronal connectivity depends on the diversification of nerve cells into functionally and molecularly distinct subtypes. While efficient methods for directed differentiation of embryonic stem cells (ESCs) into multiple principal neuronal classes have been established, only a few studies systematically examined the subtype diversity of in vitro derived nerve cells. Here we review evidence based on molecular and in vivo transplantation studies that ESC-derived spinal motor neurons and cortical layer V pyramidal neurons acquire subtype specific functional properties. We discuss similarities and differences in the role of cell intrinsic transcriptional programs, extrinsic signals and cell-cell interactions during subtype diversification of the two classes of nerve cells. We conclude that the high degree of fidelity with which differentiating ESCs recapitulate normal embryonic development provides a unique opportunity to explore developmental processes underlying specification of mammalian neuronal diversity in a simplified and experimentally accessible system. PMID:20970319

  6. Progress with nonhuman primate embryonic stem cells.

    PubMed

    Wolf, Don P; Kuo, Hung-Chih; Pau, K-Y Francis; Lester, Linda

    2004-12-01

    Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.

  7. OCT guided microinjections for mouse embryonic research

    NASA Astrophysics Data System (ADS)

    Larin, Kirill V.; Syed, Saba H.; Coughlin, Andrew J.; Wang, Shang; West, Jennifer L.; Dickinson, Mary E.; Larina, Irina V.

    2013-02-01

    Optical coherence tomography (OCT) is gaining popularity as live imaging tool for embryonic research in animal models. Recently we have demonstrated that OCT can be used for live imaging of cultured early mouse embryos (E7.5-E10) as well as later stage mouse embryos in utero (E12.5 to the end of gestation). Targeted delivery of signaling molecules, drugs, and cells is a powerful approach to study normal and abnormal development, and image guidance is highly important for such manipulations. Here we demonstrate that OCT can be used to guide microinjections of gold nanoshell suspensions in live mouse embryos. This approach can potentially be used for variety of applications such as guided injections of contrast agents, signaling molecules, pharmacological agents, cell transplantation and extraction, as well as other image-guided micromanipulations. Our studies also reveal novel potential for gold nanoshells in embryonic research.

  8. A trade-off between embryonic development rate and immune function of avian offspring is revealed by considering embryonic temperature

    PubMed Central

    Martin, Thomas E.; Arriero, Elena; Majewska, Ania

    2011-01-01

    Long embryonic periods are assumed to reflect slower intrinsic development that are thought to trade off to allow enhanced physiological systems, such as immune function. Yet, the relatively rare studies of this trade-off in avian offspring have not found the expected trade-off. Theory and tests have not taken into account the strong extrinsic effects of temperature on embryonic periods of birds. Here, we show that length of the embryonic period did not explain variation in two measures of immune function when temperature was ignored, based on studies of 34 Passerine species in tropical Venezuela (23 species) and north temperate Arizona (11 species). Variation in immune function was explained when embryonic periods were corrected for average embryonic temperature, in order to better estimate intrinsic rates of development. Immune function of offspring trades off with intrinsic rates of embryonic development once the extrinsic effects of embryonic temperatures are taken into account. PMID:21227978

  9. A trade-off between embryonic development rate and immune function of avian offspring is concealed by embryonic temperature

    USGS Publications Warehouse

    Martin, Thomas E.; Arriero, Elena; Majewska, Ania

    2011-01-01

    Long embryonic periods are assumed to reflect slower intrinsic development that are thought to trade off to allow enhanced physiological systems, such as immune function. Yet, the relatively rare studies of this trade-off in avian offspring have not found the expected trade-off. Theory and tests have not taken into account the strong extrinsic effects of temperature on embryonic periods of birds. Here, we show that length of the embryonic period did not explain variation in two measures of immune function when temperature was ignored, based on studies of 34 Passerine species in tropical Venezuela (23 species) and north temperate Arizona (11 species). Variation in immune function was explained when embryonic periods were corrected for average embryonic temperature, in order to better estimate intrinsic rates of development. Immune function of offspring trades off with intrinsic rates of embryonic development once the extrinsic effects of embryonic temperatures are taken into account.

  10. A trade-off between embryonic development rate and immune function of avian offspring is revealed by considering embryonic temperature.

    PubMed

    Martin, Thomas E; Arriero, Elena; Majewska, Ania

    2011-06-23

    Long embryonic periods are assumed to reflect slower intrinsic development that are thought to trade off to allow enhanced physiological systems, such as immune function. Yet, the relatively rare studies of this trade-off in avian offspring have not found the expected trade-off. Theory and tests have not taken into account the strong extrinsic effects of temperature on embryonic periods of birds. Here, we show that length of the embryonic period did not explain variation in two measures of immune function when temperature was ignored, based on studies of 34 Passerine species in tropical Venezuela (23 species) and north temperate Arizona (11 species). Variation in immune function was explained when embryonic periods were corrected for average embryonic temperature, in order to better estimate intrinsic rates of development. Immune function of offspring trades off with intrinsic rates of embryonic development once the extrinsic effects of embryonic temperatures are taken into account.

  11. Intra-atrial conduction block mimicking atrioventricular nodal block after multiple catheter ablation procedures for atrial tachycardia in a patient with cardiomyopathy.

    PubMed

    Chugh, Aman; Yokokawa, Miki; Baman, Timir; Bogun, Frank; Wu, Audrey

    2012-11-01

    A 42-year-old woman with a history of cardiomyopathy and multiple ablation procedures for atrial tachycardia developed intra-atrial conduction block that mimicked atrioventricular (AV) nodal block during radiofrequency ablation at the cavotricuspid isthmus. She was treated with atrial pacing (from the coronary sinus), which overcame intra-atrial conduction block and resulted in AV nodal conduction.

  12. Embryonic stem cell factors and pancreatic cancer

    PubMed Central

    Herreros-Villanueva, Marta; Bujanda, Luis; Billadeau, Daniel D; Zhang, Jin-San

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic tumor, is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its early- metastasis and lack of response to chemotherapy and radiation. Recent research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells (CSCs), a small and distinct population of cancer cells that mediates tumoregenesis, metastasis and resistance to standard treatments. Thus, CSCs could be a target for more effective treatment options. Interestingly, pancreatic CSCs are subject to regulation by some of key embryonic stem cell (ESC) transctiption factors abberently expressed in PDAC, such as SOX2, OCT4 and NANOG. ESC transcription factors are important DNA-binding proteins present in both embryonic and adult somatic cells. The critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also tumorigenesis. Here we provide an overview of stem cell transcription factors, particularly SOX2, OCT4, and NANOG, on their expression and function in pancreatic cancer. In contrast to embryonic stem cells, in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes, de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal, de-differentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver genes. Thus, targeting ESC factors, particularly SOX2, could be a worthy strategy for pancreatic cancer therapy. PMID:24605024

  13. Embryonic stem cell factors and pancreatic cancer.

    PubMed

    Herreros-Villanueva, Marta; Bujanda, Luis; Billadeau, Daniel D; Zhang, Jin-San

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic tumor, is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its early- metastasis and lack of response to chemotherapy and radiation. Recent research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells (CSCs), a small and distinct population of cancer cells that mediates tumoregenesis, metastasis and resistance to standard treatments. Thus, CSCs could be a target for more effective treatment options. Interestingly, pancreatic CSCs are subject to regulation by some of key embryonic stem cell (ESC) transctiption factors abberently expressed in PDAC, such as SOX2, OCT4 and NANOG. ESC transcription factors are important DNA-binding proteins present in both embryonic and adult somatic cells. The critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also tumorigenesis. Here we provide an overview of stem cell transcription factors, particularly SOX2, OCT4, and NANOG, on their expression and function in pancreatic cancer. In contrast to embryonic stem cells, in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes, de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal, de-differentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver genes. Thus, targeting ESC factors, particularly SOX2, could be a worthy strategy for pancreatic cancer therapy.

  14. Hedgehog Signalling in the Embryonic Mouse Thymus

    PubMed Central

    Saldaña, José Ignacio; Crompton, Tessa

    2016-01-01

    T cells develop in the thymus, which provides an essential environment for T cell fate specification, and for the differentiation of multipotent progenitor cells into major histocompatibility complex (MHC)-restricted, non-autoreactive T cells. Here we review the role of the Hedgehog signalling pathway in T cell development, thymic epithelial cell (TEC) development, and thymocyte–TEC cross-talk in the embryonic mouse thymus during the last week of gestation. PMID:27504268

  15. Exogenous supplementation of Activin A enhances germ cell differentiation of human embryonic stem cells.

    PubMed

    Duggal, Galbha; Heindryckx, Björn; Warrier, Sharat; Taelman, Jasin; Van der Jeught, Margot; Deforce, Dieter; Chuva de Sousa Lopes, Susana; De Sutter, Petra

    2015-05-01

    Human embryonic stem cells (hESCs) derived in the presence of Activin A (ActA) demonstrate an increased differentiation propensity toward the germ cell lineage. In addition, mouse epiblast stem cells and mouse epiblast-like cells are poised toward germ cell differentiation and are derived in the presence of ActA. We therefore investigated whether supplementation with ActA enhances in vitro hESC differentiation toward germ cell lineage. ActA up-regulated early primordial germ cell (PGC) genes STELLA/DPPA3 (developmental pluripotency associated 3) and tyrosine kinase receptor cKIT in both ActA-derived and standard-derived hESCs indicating its role in priming hESCs toward the PGC lineage. Indeed, ActA plus bone morphogenic protein 4 (BMP4) strongly increased germ cell differentiation potential of hESCs based on the high expression of late PGC markers DAZL (deleted in azoospermia-like) and VASA/DDX4 (DEAD-box polypeptide 4) at mRNA and protein level. Hence, the combination of ActA with BMP4 provides an additional boost for hESCs to develop into postmigratory germ cells. Together with increased VASA expression in the presence of ActA and BMP4, we also observed up-regulation of endoderm-specific genes GATA4 (GATA binding protein 4) and GATA6. Finally, we were able to further mature these in vitro-derived PGC-like cells (PGCLCs) by culturing them in in vitro maturation (IVM) medium, resulting in the formation of germ cell-like clusters and induction of meiotic gene expression. In conclusion, we demonstrate for the first time a synergism between ActA and BMP4 in facilitating germ cell-directed differentiation of hESCs, which is enhanced by extended culture in IVM medium, as shown by cytoplasmic VASA-expressing PGCLCs. We propose a novel relationship between the endoderm and germ cell lineage during hESC differentiation.

  16. Derivation of stromal (skeletal and mesenchymal) stem-like cells from human embryonic stem cells.

    PubMed

    Mahmood, Amer; Harkness, Linda; Abdallah, Basem M; Elsafadi, Mona; Al-Nbaheen, May S; Aldahmash, Abdullah; Kassem, Moustapha

    2012-11-20

    Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESCs) is a prerequisite for their use in clinical applications. However, there is no standard protocol for differentiating hESCs into osteoblastic cells. The aim of this study was to identify the emergence of a human stromal (mesenchymal and skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESCs in a feeder-free environment using serum replacement and as suspension aggregates (embryoid bodies; hEBs). Over a 20 day developmental period, the hEBs demonstrated increasing enrichment for cells expressing hMSC markers: CD29, CD44, CD63, CD56, CD71, CD73, CD105, CD106, and CD166 as revealed by immunohistochemical staining and flow cytometry (fluorescence-activated cell sorting) analysis. Ex vivo differentiation of hEBs using bone morphogenic protein 2 (BMP2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold, revealed bone and cartilage, and fibrous tissue elements after 8 weeks. These tissues were of human origin and there was no evidence of differentiation to nonmesodermal tissues. hEBs implanted in the absence of HA/TCP formed vacuolated tissue containing glandular, fibrous and muscle-like tissue elements. Conversely, implantation of undifferentiated hESCs resulted in the formation of a teratoma containing a mixture of endodermal, mesodermal, and ectodermal tissues. Our study demonstrates that hMSC-like cells can be obtained from hESCs and they can be induced to form skeletal tissues in vivo when combined with HA/TCP. These findings are relevant for tissue engineering and suggest that differentiated hEBs can provide an unlimited source for

  17. Embryonic development of Pelteobagrus fulvidraco (Richardson, 1846)

    NASA Astrophysics Data System (ADS)

    Wang, Weimin; Abbas, Khalid; Yan, Ansheng

    2006-12-01

    For production enhancement and procedure upgrade, the developmental phases of laboratory-reared eggs of catfish Pelteobagrus fulvidraco were investigated. Twenty mature females and 10 males were collected from Dadongmen wholesale fisheries market in Wuhan City on May 8, 2003. Zygotes were stripped from mature fish after hormone-induced ovulation, fertilized, and incubated through whole embryonic development. The fertilized eggs were stocked in density of 100 eggs/L in white square tanks of 10 L. Incubation water was dechlorinated tap water with continuous aeration. The tanks were lit directly with 60 W fluorescent bulbs with a 12 light: 12 dark photoperiod. Water temperature, dissolved oxygen and pH were 29.0±0.5°C, 6.7±0.4 mg/L and 7.4±2, respectively. The results showed that the eggs of P. fulvidraco were yellow, sticky and contained much yolk. The mean diameter of fertilized eggs was 2.03 mm. At the water temperature of 29.0±0.5°C, the ontogenesis spent about 33 h after fertilization. From fertilization to hatching, the embryonic development can be divided into 30 40 phases, which varies in the emphasis and direction of development. The detailed embryonic movement was also described.

  18. Mechanical signaling coordinates the embryonic heartbeat.

    PubMed

    Chiou, Kevin K; Rocks, Jason W; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F; Prosser, Benjamin L; Discher, Dennis E; Liu, Andrea J

    2016-08-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts-consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  19. [Heart tissue from embryonic stem cells].

    PubMed

    Zimmermann, W-H

    2008-09-01

    Embryonic stem cells can give rise to all somatic cells, making them an attractive cell source for tissue engineering applications. The propensity of cells to form tissue-like structures in a culture dish has been well documented. We and others made use of this intrinsic property to generate bioartificial heart muscle. First proof-of-concept studies involved immature heart cells mainly from fetal chicken, neonatal rats and mice. They eventually provided evidence that force-generating heart muscle can be engineered in vitro. Recently, the focus shifted to the application of stem cells to eventually enable the generation of human heart muscle and reach following long-term goals: (1) development of a simplified in vitro model of heart muscle development; (2) generation of a human test-bed for drug screening and development; (3) allocation of surrogate heart tissue to myocardial repair applications. This overview will provide the background for cell-based myocardial repair, introduce the main myocardial tissue engineering concepts, discuss the use of embryonic and non-embryonic stem cells, and lays out the potential direct and indirect therapeutic use of human tissue engineered myocardium.

  20. Isolation of Murine Embryonic Hemogenic Endothelial Cells

    PubMed Central

    Marcelo, Kathrina L.; Hirschi, Karen K.

    2016-01-01

    The specification of hemogenic endothelial cells from embryonic vascular endothelium occurs during brief developmental periods within distinct tissues, and is necessary for the emergence of definitive HSPC from the murine extra embryonic yolk sac, placenta, umbilical vessels, and the embryonic aorta-gonad-mesonephros (AGM) region. The transient nature and small size of this cell population renders its reproducible isolation for careful quantification and experimental applications technically difficult. We have established a fluorescence-activated cell sorting (FACS)-based protocol for simultaneous isolation of hemogenic endothelial cells and HSPC during their peak generation times in the yolk sac and AGM. We demonstrate methods for dissection of yolk sac and AGM tissues from mouse embryos, and we present optimized tissue digestion and antibody conjugation conditions for maximal cell survival prior to identification and retrieval via FACS. Representative FACS analysis plots are shown that identify the hemogenic endothelial cell and HSPC phenotypes, and describe a methylcellulose-based assay for evaluating their blood forming potential on a clonal level. PMID:27341393

  1. Performance of seminal and nodal roots of wheat in stagnant solution: K+ and P uptake and effects of increasing O2 partial pressures around the shoot on nodal root elongation.

    PubMed

    Wiengweera, Amara; Greenway, Hank

    2004-09-01

    Roots of intact wheat plants were grown for 7-12 d in stagnant nutrient solution, containing 0.1% agar, to mimic the lack of convection in waterlogged soil. Net K+ and P uptakes by seminal and nodal roots were measured separately using a split root system. For seminal roots in stagnant solution, net uptakes as a percentage of aerated roots were between 0% and 16% for P, while K+ ranged between 15% uptake and 54% loss. For the more waterlogging-tolerant nodal roots, net uptakes in stagnant nutrient solution, as a percentage of aerated roots, were 31-73% for P and 69-115% for K+. Elongation rates of nodal roots in stagnant nutrient were about 35-43% of those for roots in aerated solution. This partial inhibition occurred in these nodal roots despite their 15% porosity (v/v). Elevation of O2 partial pressures around the shoots to 40 kPa and then to 80 kPa substantially accelerated nodal root elongation in stagnant solution, demonstrating that most of the inhibition seen with ambient O2 around the shoots was associated with a restricted O2 supply to these nodal roots. Thus, in wheat nodal roots, with a partial pressure of 20 kPa O2 around the shoots, O2 diffusion from the shoots did not completely relieve the restrictions on elongation resulting from stagnancy in the nutrient solution. These results contrast with those in the literature for rice, in which roots function efficiently in stagnant solutions (0.1% agar). So, when wheat roots are aerenchymatous there are still restrictions to O2 diffusion in the gas space continuum between the atmosphere and the functional tissues of the roots. This poor acclimation must have been due to inefficiency of the aerenchymatous axes, which may include persistence of anoxic steles, and/or restricted O2 diffusion in other parts of the gas space continuum, in either the shoots and shoot-root junction or in the root tip.

  2. NODAL secreted by male germ cells regulates the proliferation and function of human Sertoli cells from obstructive azoospermia and nonobstructive azoospermia patients

    PubMed Central

    Tian, Ru-Hui; Yang, Shi; Zhu, Zi-Jue; Wang, Jun-Long; Liu, Yun; Yao, Chencheng; Ma, Meng; Guo, Ying; Yuan, Qingqing; Hai, Yanan; Huang, Yi-Ran; He, Zuping; Li, Zheng

    2015-01-01

    This study was designed to explore the regulatory effects of male germ cell secreting factor NODAL on Sertoli cell fate decisions from obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) patients. Human Sertoli cells and male germ cells were isolated using two-step enzymatic digestion and SATPUT from testes of azoospermia patients. Expression of NODAL and its multiple receptors in human Sertoli cells and male germ cells were characterized by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. Human recombinant NODAL and its receptor inhibitor SB431542 were employed to probe their effect on the proliferation of Sertoli cells using the CCK-8 assay. Quantitative PCR and Western blots were utilized to assess the expression of Sertoli cell functional genes and proteins. NODAL was found to be expressed in male germ cells but not in Sertoli cells, whereas its receptors ALK4, ALK7, and ACTR-IIB were detected in Sertoli cells and germ cells, suggesting that NODAL plays a regulatory role in Sertoli cells and germ cells via a paracrine and autocrine pathway, respectively. Human recombinant NODAL could promote the proliferation of human Sertoli cells. The expression of cell cycle regulators, including CYCLIN A, CYCLIN D1 and CYCLIN E, was not remarkably affected by NODAL signaling. NODAL enhanced the expression of essential growth factors, including GDNF, SCF, and BMP4, whereas SB431542 decreased their levels. There was not homogeneity of genes changes by NODAL treatment in Sertoli cells from OA and Sertoli cell-only syndrome (SCO) patients. Collectively, this study demonstrates that NODAL produced by human male germ cells regulates proliferation and numerous gene expression of Sertoli cells. PMID:26289399

  3. Lunar nodal tide and distance to the moon during the Precambrian

    NASA Technical Reports Server (NTRS)

    Walker, J. C. G.; Zahnle, K. J.

    1986-01-01

    The first direct determination of the lunar distance in the Precambrian is presented. A 23.3 + or - 0.3 yr periodicity preserved in 2500 Myr BP Australian banded iron formation is interpreted as reflecting the climatic influence of the lunar nodal tide, which has been detected with its modern 18.6-yr periodicity in some modern climate records. The lunar distance at 2500 Myr BP would then have been about 52 earth radii. The implied history of precambrian tidal friction is in accord with both the more recent paleontological evidence and the long-term stability of the lunar orbit. The length of the Milankovitch cycles that modulate the ice ages today also evolve with the earth-moon system. Their detection in the Precambrian sedimentary record would then permit an independent determination of the lunar distance.

  4. Sick sinus syndrome and atrial fibrillation in older persons - A view from the sinoatrial nodal myocyte.

    PubMed

    Monfredi, O; Boyett, M R

    2015-06-01

    Sick sinus syndrome remains a highly relevant clinical entity, being responsible for the implantation of the majority of electronic pacemakers worldwide. It is an infinitely more complex disease than it was believed when first described in the mid part of the 20th century. It not only involves the innate leading pacemaker region of the heart, the sinoatrial node, but also the atrial myocardium, predisposing to atrial tachydysrhythmias. It remains controversial as to whether the dysfunction of the sinoatrial node directly causes the dysfunction of the atrial myocardium, or vice versa, or indeed whether these two aspects of the condition arise through some related underlying pathological mechanism, such as extracellular matrix remodeling, i.e., fibrosis. This review aims to shed new light on the myriad possible contributing factors in the development of sick sinus syndrome, with a particular focus on the sinoatrial nodal myocyte. This article is part of a Special Issue entitled CV Aging.

  5. Unified Theory of PT and CP Invariant Topological Metals and Nodal Superconductors.

    PubMed

    Zhao, Y X; Schnyder, Andreas P; Wang, Z D

    2016-04-15

    As PT and CP symmetries are fundamental in physics, we establish a unified topological theory of PT and CP invariant metals and nodal superconductors, based on the mathematically rigorous KO theory. Representative models are constructed for all nontrivial topological cases in dimensions d=1, 2, and 3, with their exotic physical meanings being elucidated in detail. Intriguingly, it is found that the topological charges of Fermi surfaces in the bulk determine an exotic direction-dependent distribution of topological subgap modes on the boundaries. Furthermore, by constructing an exact bulk-boundary correspondence, we show that the topological Fermi points of the PT and CP invariant classes can appear as gapless modes on the boundary of topological insulators with a certain type of anisotropic crystalline symmetry.

  6. A rare case of extra nodal Rosai-Dorfman disease with isolated multifocal osseous manifestation

    PubMed Central

    Patel, Maharshi H; Jambhekar, Kedar R; Pandey, Tarun; Ram, Roopa

    2015-01-01

    Sinus histiocytosis with massive lymphadenopathy (SHML) or Rosai–Dorfman disease is a non-neoplastic condition which typically presents as massive, bilateral cervical lymphadenopathy and can involve multiple extranodal organ systems such as skin, eyes, and upper respiratory tract in about 28% cases. Bone lesions in association with nodal disease are seen in less than 10% cases. Isolated bone involvement as the only manifestation of SHML is extremely rare, with less than 50 cases reported in the literature. We report a very uncommon case of Rosai–Dorfman disease with isolated multifocal osseous involvement as the only presenting feature, involving about 10 different sites with no lymphadenopathy or other organ system involvement. PMID:26288524

  7. [Dual atrioventricular nodal conduction and arrhythmia with severe hemodynamic alterations during liver retransplantation].

    PubMed

    Zaballos, M; Jimeno, C; Jiménez, C; Fraile, J R; Almendral; García de Lucas, E

    2005-01-01

    We report the case of a man who developed tachycardia caused by atrioventricular reentry related to dual nodal conduction during liver retransplantation. The hemodynamic alterations were severe. Arrhythmia and altered cardiac conduction are potential complications of liver transplantation. The development of tachyarrhythmias--atrial fibrillation as well as episodes of supraventricular and ventricular tachycardia and bradycardia--have been described. Such arrhythmias tend to occur particularly during reperfusion of the graft. Risk factors implicated are the severe ion imbalances, acid-base imbalance, and hypothermia that accompany the reperfusion of a new organ. A review of the possible pathogenic and etiological mechanisms that lead to arrhythmia in patients with end-stage liver disease is provided.

  8. Quantum criticality and nodal superconductivity in the FeAs-based superconductor KFe2As2.

    PubMed

    Dong, J K; Zhou, S Y; Guan, T Y; Zhang, H; Dai, Y F; Qiu, X; Wang, X F; He, Y; Chen, X H; Li, S Y

    2010-02-26

    The in-plane resistivity rho and thermal conductivity kappa of the FeAs-based superconductor KFe2As2 single crystal were measured down to 50 mK. We observe non-Fermi-liquid behavior rho(T) approximately T{1.5} at H{c{2}}=5 T, and the development of a Fermi liquid state with rho(T) approximately T{2} when further increasing the field. This suggests a field-induced quantum critical point, occurring at the superconducting upper critical field H{c{2}}. In zero field, there is a large residual linear term kappa{0}/T, and the field dependence of kappa_{0}/T mimics that in d-wave cuprate superconductors. This indicates that the superconducting gaps in KFe2As2 have nodes, likely d-wave symmetry. Such a nodal superconductivity is attributed to the antiferromagnetic spin fluctuations near the quantum critical point.

  9. Nodal gap structure and order parameter symmetry of the unconventional superconductor UPt₃

    DOE PAGESBeta

    Gannon, W. J.; Halperin, W. P.; Rastovski, C.; Schlesinger, K. J.; Hlevyack, J.; Eskildsen, M. R.; Vorontsov, A. B.; Gavilano, J.; Gasser, U.; Nagy, G.

    2015-02-01

    Spanning a broad range of physical systems, complex symmetry breaking is widely recognized as a hallmark of competing interactions. This is exemplified in superfluid ³He which has multiple thermodynamic phases with spin and orbital quantum numbers S = 1 and L = 1, that emerge on cooling from a nearly ferromagnetic Fermi liquid. The heavy fermion compound UPt₃ exhibits similar behavior clearly manifest in its multiple superconducting phases. However, consensus as to its order parameter symmetry has remained elusive. Our small angle neutron scattering measurements indicate a linear temperature dependence of the London penetration depth characteristic of nodal structure ofmore » the order parameter. Our theoretical analysis is consistent with assignment of its symmetry to an L = 3 odd parity state for which one of the three thermodynamic phases in non-zero magnetic field is chiral.« less

  10. Topological semimetals with triply degenerate nodal points in θ -phase tantalum nitride

    NASA Astrophysics Data System (ADS)

    Weng, Hongming; Fang, Chen; Fang, Zhong; Dai, Xi

    2016-06-01

    Using first-principles calculation and symmetry analysis, we propose that θ -TaN is a topological semimetal having a new type of point nodes, i.e., triply degenerate nodal points. Each node is a band crossing between degenerate and nondegenerate bands along the high-symmetry line in the Brillouin zone, and is protected by crystalline symmetries. Such new type of nodes will always generate singular touching points between different Fermi surfaces and three-dimensional spin texture around them. Breaking the crystalline symmetry by external magnetic field or strain leads to various topological phases. By studying the Landau levels under a small field along the c axis, we demonstrate that the system has a new quantum anomaly that we call "helical anomaly.'

  11. Diagnosis of non-nodal paratracheobronchial lesions by linear endobronchial ultrasound.

    PubMed

    Lourido, Tamara; Botana, Maribel; Leiro, Virginia; Núñez, Manuel; Fernández-Villar, Alberto

    2013-08-01

    Linear endobronchial ultrasound (EBUS) allows samples of lesions close to the airways to be obtained, as it enables aspiration to be performed under visual control in real time, opening new possibilities for minimally invasive examination of the mediastinum. While there are many publications on its usefulness in the study of mediastinal or hilar lymphadenopathies, there are few that analyse the role of EBUS-guided transbronchial needle aspiration for the diagnosis of other lesions adjacent to the airways or digestive tract. We describe the characteristics and results obtained in a series of 26 cases of non-nodal lesions of different aetiologies studied by EBUS- guided transbronchial needle aspiration through the airways or oesophagus, demonstrating the usefulness and safety of this technique in the diagnosis of these types of lesions.

  12. The Titan -1:0 Nodal Bending Wave in Saturn's Ring C.

    PubMed

    Rosen, P A; Lissauer, J J

    1988-08-01

    The most prominent oscillatory feature observed in the Voyager 1 radio occultation of Saturn's rings is identified as a one-armed spiral bending wave excited by Titan's -1:0 nodal inner vertical resonance. Ring partides in a bending wave move in coherently inclined orbits, warping the local mean plane of the rings. The Titan -1:0 wave is the only known bending wave that propagates outward, away from Saturn, and the only spiral wave yet observed in which the wave pattern rotates opposite to the orbital direction of the ring particles. It is also the first bending wave identified in ring C. Modeling the observed feature with existing bending wave theory gives a surface mass density of approximately 0.4 g/cm(2) outside the wave region and a local ring thickness of [unknown]5 meters, and suggests that surface mass density is not constant in the wave region.

  13. Increased mesquite gum formation in nodal explants cultures after treatment with a microbial biomass preparation.

    PubMed

    Orozco-Villafuerte, Juan; Buendía-González, Leticia; Cruz-Sosa, Francisco; Vernon-Carter, Eduardo J

    2005-08-01

    Prosopis laevigata nodal explants cultures were established in Murashige and Skoog medium. Simultaneously these cultures were subjected to stress with biotic elicitors and an environmental factor (temperature increase to promote heat stress) in order to promote and increase exuded mesquite gum production. The biotic elicitors were: Aspergillus nidulans and Pseudomonas pseudoalcaligenes both used in concentrations of 10, 20 and 30 mg, whereas the environmental condition was different incubation temperatures (25, 35 and 40 degrees C). The greatest gum production (approximately 13 mg of pooled gum from 100 explants after 14 days incubation) took place when the culture medium was added 10, 20 and 30 mg of autoclaved fungal mycelium of A. nidulans or 30 mg of autoclaved bacterial biomass of P. pseudoalcaligenes in combination with an incubation temperature of 35 degrees C. These treatments were non-significantly different among themselves (P < 0.05), but were significantly different to the rest of the treatments (P > 0.05).

  14. Lunar nodal tide and distance to the moon during the Precambrian

    NASA Astrophysics Data System (ADS)

    Walker, J. C. G.; Zahnle, K. J.

    1986-04-01

    The first direct determination of the lunar distance in the Precambrian is presented. A 23.3 + or - 0.3 yr periodicity preserved in 2500 Myr BP Australian banded iron formation is interpreted as reflecting the climatic influence of the lunar nodal tide, which has been detected with its modern 18.6-yr periodicity in some modern climate records. The lunar distance at 2500 Myr BP would then have been about 52 earth radii. The implied history of precambrian tidal friction is in accord with both the more recent paleontological evidence and the long-term stability of the lunar orbit. The length of the Milankovitch cycles that modulate the ice ages today also evolve with the earth-moon system. Their detection in the Precambrian sedimentary record would then permit an independent determination of the lunar distance.

  15. Analysis of nodal point pollution, variability, and sustainability in mesohaline tidal creeks.

    PubMed

    Muller, Andrew; Muller, Diana

    2014-08-15

    Mesohaline tidal creeks are critical since they may lie at the crossroads of aquatic habitat and urban/sub-urban pressures. The emphasis of this study was to determine the water quality stressor variations within and between tidal creeks and determine whether they serve as nodes of pollutants into the sub-estuary. Measurements of water quality stressors were conducted over a six-year period. The study revealed that characterizing the variability of individual tidal creeks is critical to understanding the process and impacts of stressors in sub-estuarine environments and that the tidal creeks are actually nodal points of sediment and nutrient pollution. This results in hypoxia being controlled within tidal creeks rather than being imported from the parent estuary. The calculated metrics were then used to create a Sustainability Characterization Map. Methods incorporated in this study would be of value to restoration managers, and in the decision-making process of urban and suburban watershed planners.

  16. Nodal gap structure and order parameter symmetry of the unconventional superconductor UPt₃

    SciTech Connect

    Gannon, W. J.; Halperin, W. P.; Rastovski, C.; Schlesinger, K. J.; Hlevyack, J.; Eskildsen, M. R.; Vorontsov, A. B.; Gavilano, J.; Gasser, U.; Nagy, G.

    2015-02-01

    Spanning a broad range of physical systems, complex symmetry breaking is widely recognized as a hallmark of competing interactions. This is exemplified in superfluid ³He which has multiple thermodynamic phases with spin and orbital quantum numbers S = 1 and L = 1, that emerge on cooling from a nearly ferromagnetic Fermi liquid. The heavy fermion compound UPt₃ exhibits similar behavior clearly manifest in its multiple superconducting phases. However, consensus as to its order parameter symmetry has remained elusive. Our small angle neutron scattering measurements indicate a linear temperature dependence of the London penetration depth characteristic of nodal structure of the order parameter. Our theoretical analysis is consistent with assignment of its symmetry to an L = 3 odd parity state for which one of the three thermodynamic phases in non-zero magnetic field is chiral.

  17. Identification and expression of Smads associated with TGF-beta/activin/nodal signaling pathways in the rainbow trout (Oncorhynuchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Smad proteins are essential components of the TGF-beta/activin/nodal family signaling pathway. We report the identification and characterization of transcripts representing 3 receptor Smads (Smad2a, Smad2b, Smad3), 2 common Smads (Smad4a, Smad4b) and one inhibitory Smad (Smad7). Phylogenetic an...

  18. Nodal signalling in Xenopus: the role of Xnr5 in left/right asymmetry and heart development

    PubMed Central

    Tadjuidje, Emmanuel; Kofron, Matthew; Mir, Adnan; Wylie, Christopher; Heasman, Janet; Cha, Sang-Wook

    2016-01-01

    Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. Here, we examine the role of Xnr5. We find it acts at the late blastula stage as a mesoderm inducer and repressor of ectodermal gene expression, a role it shares with Vg1. However, unlike Vg1, Xnr5 depletion reduces the expression of the nodal family member xnr1 at the gastrula stage. It is also required for left/right laterality by controlling the expression of the laterality genes xnr1, antivin (lefty) and pitx2 at the tailbud stage. In Xnr5-depleted embryos, the heart field is established normally, but symmetrical reduction in Xnr5 levels causes a severely stunted midline heart, first evidenced by a reduction in cardiac troponin mRNA levels, while left-sided reduction leads to randomization of the left/right axis. This work identifies Xnr5 as the earliest step in the signalling pathway establishing normal heart laterality in Xenopus. PMID:27488374

  19. Theory of nodal s±-wave pairing symmetry in the Pu-based 115 superconductor family

    PubMed Central

    Das, Tanmoy; Zhu, Jian-Xin; Graf, Matthias J.

    2015-01-01

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s+− wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scattering channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s+− wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry. PMID:25721375

  20. Theory of nodal s±-wave pairing symmetry in the Pu-based 115 superconductor family

    SciTech Connect

    Das, Tanmoy; Zhu, Jian -Xin; Graf, Matthias J.

    2015-02-27

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s⁺⁻ wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scattering channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s⁺⁻ wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.

  1. Theory of nodal s±-wave pairing symmetry in the Pu-based 115 superconductor family

    DOE PAGESBeta

    Das, Tanmoy; Zhu, Jian -Xin; Graf, Matthias J.

    2015-02-27

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s⁺⁻ wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scattering channel,more » which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s⁺⁻ wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.« less

  2. Finite elements using absolute nodal coordinates for large-deformation flexible multibody dynamics

    NASA Astrophysics Data System (ADS)

    Dmitrochenko, Oleg

    2008-06-01

    A family of structural finite elements using a modern absolute nodal coordinate formulation (ANCF) is discussed in the paper with many applicationsE This approach has been initiated in 1996 by A. Shabana. It introduces large displacements of 2D/3D finite elements relative to the global reference frame without using any local frame. The elements employ finite slopes as nodal variables and can be considered as generalizations of ordinary finite elements that use infinitesimal slopes. In contrast to other large deformation formulations, the equations of motion contain constant mass matrices and generalized gravity forces as well as zero centrifugal and Coriolis inertia forces. The only nonlinear term is a vector of elastic forces. This approach allows applying known abstractions of real elastic bodies: Euler-Bernoulli beams, Timoshenko beams and more general models as well as Kirchhoff and Mindlin plate theories. Shabana et al. proposed a sub-family of thick beam and plate finite elements with large deformations and employ the 3D theory of continuum mechanics. Despite the universality of such approach it has to use extra degrees of freedom when simulating thin beams and plates, which case is most important. In our research, we propose another sub-family of thin beams as well as rectangular and triangle plates. We use Kirchhoff plate theory with nonlinear strain-displacement relationships to obtain elastic forces. A number of static and dynamic simulation examples of problems with 2D/3D very elastic beams and plate underwent large displacements and/or deformations will be shown in the presentation.

  3. Asynchronous collision integrators: Explicit treatment of unilateral contact with friction and nodal restraints

    PubMed Central

    Wolff, Sebastian; Bucher, Christian

    2013-01-01

    This article presents asynchronous collision integrators and a simple asynchronous method treating nodal restraints. Asynchronous discretizations allow individual time step sizes for each spatial region, improving the efficiency of explicit time stepping for finite element meshes with heterogeneous element sizes. The article first introduces asynchronous variational integration being expressed by drift and kick operators. Linear nodal restraint conditions are solved by a simple projection of the forces that is shown to be equivalent to RATTLE. Unilateral contact is solved by an asynchronous variant of decomposition contact response. Therein, velocities are modified avoiding penetrations. Although decomposition contact response is solving a large system of linear equations (being critical for the numerical efficiency of explicit time stepping schemes) and is needing special treatment regarding overconstraint and linear dependency of the contact constraints (for example from double-sided node-to-surface contact or self-contact), the asynchronous strategy handles these situations efficiently and robust. Only a single constraint involving a very small number of degrees of freedom is considered at once leading to a very efficient solution. The treatment of friction is exemplified for the Coulomb model. Special care needs the contact of nodes that are subject to restraints. Together with the aforementioned projection for restraints, a novel efficient solution scheme can be presented. The collision integrator does not influence the critical time step. Hence, the time step can be chosen independently from the underlying time-stepping scheme. The time step may be fixed or time-adaptive. New demands on global collision detection are discussed exemplified by position codes and node-to-segment integration. Numerical examples illustrate convergence and efficiency of the new contact algorithm. Copyright © 2013 The Authors. International Journal for Numerical Methods in

  4. Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system

    PubMed Central

    Çolakoğlu, Gülsen; Bergstrom-Tyrberg, Ulrika; Berglund, Erik O.; Ranscht, Barbara

    2014-01-01

    Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expression on oligodendrocytes in vivo, and progressive accumulation at nodes of Ranvier and paranodes during postnatal mouse development. Nodal and paranodal expression stabilized in mature myelin, but overall membranous expression diminished. Contactin-1–deficiency disrupted paranodal junction formation as evidenced by loss of Caspr, mislocalized potassium Kv1.2 channels, and abnormal myelin terminal loops. Reduced numbers and impaired maturation of sodium channel clusters accompanied this phenotype. Histological, electron microscopic, and biochemical analyses uncovered significant hypomyelination in Contactin-1–deficient central nerves, with up to 60% myelin loss. Oligodendrocytes were present in normal numbers, albeit a minor population of neuronal/glial antigen 2-positive (NG2+) progenitors lagged in maturation by postnatal day 18, when the mouse null mutation was lethal. Major contributing factors to hypomyelination were defects in the generation and organization of myelin membranes, as judged by electron microscopy and quantitative analysis of oligodendrocyte processes labeled by GFP transgenically expressed from the proteolipid protein promoter. These data reveal that Contactin-1 regulates both myelin formation and organization of nodal and paranodal domains in the CNS. These multiple roles distinguish central Contactin-1 functions from its specific role at paranodes in the periphery, and emphasize mechanistic differences in central and peripheral myelination. PMID:24385581

  5. Pharmacologic intervention in axonal excitability: in vivo assessment of nodal persistent sodium currents in human neuropathies.

    PubMed

    Kuwabara, Satoshi; Misawa, Sonoko

    2008-01-01

    Axonal excitability testing can provide new insights into the ionic mechanisms underlying the pathophysiology of hyperexcitability of motor and sensory axons in human neuropathies. Threshold tracking was developed in the 1990's to non-invasively measure a number of axonal excitability indices that depend on sodium and potassium channel function, and this makes it possible to monitor the effects of pharmacologic intervention with ion channel modulators. This paper reviews recent advances in ionic-pathophysiological studies in humans. (1) Neuropathic pain or muscle cramp/fasciculation is partly caused by hyperexcitability of the injured axons. The enhanced excitability can result from altered ion channel function; such as an increase in persistent sodium currents. Persistent sodium currents can be reliably estimated using threshold tracking. In peripheral neuropathy, persistent sodium currents usually increase possibly due to over-expression of sodium channels associated with axonal regeneration, and could be responsible for ectopic firings. Administration of sodium channel blockers such as mexiletine, results in marked alleviation of muscle cramping in parallel with a decrease in nodal persistent sodium currents. (2) In diabetic neuropathy, the activation of the polyol pathway mediated by an enzyme, aldose reductase, leads to reduced Na(+)/K(+) pump activity, and intra-axonal sodium accumulation; sodium currents are reduced presumably due to decreased trans-axonal sodium gradient. Aldose reductase inhibitiors improve nodal sodium currents, as well as nerve conduction, and this can be objectively assessed by threshold tracking. Studies of ion-channel pathophysiology in human subjects have recently begun. Investigating ionic mechanisms by monitoring the corresponding ionic currents. is of clinical relevance, because once a specific ionic conductance is identified, pharmacologic blocking or modulation could provide a new therapeutic option. PMID:20021424

  6. The Association Between Biological Subtype and Isolated Regional Nodal Failure After Breast-Conserving Therapy

    SciTech Connect

    Wo, Jennifer Y.; Taghian, Alphonse G.; Nguyen, Paul L.; Raad, Rita Abi; Sreedhara, Meera B.A.; Bellon, Jennifer R.; Wong, Julia S.; Gadd, Michele A.; Smith, Barbara L.; Harris, Jay R.

    2010-05-01

    Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status-, progesterone receptor status-, and HER-2-status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients.

  7. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  8. Debunking the lunar nodal tide in sea level data from the Northwest European shelf

    NASA Astrophysics Data System (ADS)

    Schmith, Torben; Thejll, Peter; Nielsen, Jacob W.

    2016-04-01

    In a recent study (Hansen, et al, 2015. Sea-Level Forcing by Synchronization of 56- and 74-Year Oscillations with the Moon's Nodal Tide on the Northwest European Shelf (Eastern North Sea to Central Baltic Sea). Journal of Coastal Research, 31(5), 1041 - 1056, hereafter 'HAK'), the existence of an 18.6 year lunar nodal tide signal of considerable strength and other periodic signals in the North Sea -- Baltic Sea area is claimed. We criticize important aspects of the analysis presented in HAK and thereby cast doubt on their conclusions. HAK claim that 18.6 year variations in sea level are predicted by tidal theory, but this is not the case in general and therefore the existence of such variations must be explicitly shown. We calculate the amplitude spectrum of the annual sea level by harmonic analysis and find no significant peaks at the periods claimed by HAK. Next, we used the results given by HAK to reconstruct their decomposition, and formed the residuals by subtracting the decomposition from the original data. We found that a strong variability near 18.6 years in the residuals, showing that the decomposition by HAK overrepresents the variability at this period. This motivated us to redo HAK's analysis following their prescription and we found a seven times lower amplitude for the 18.6 year periodicity than claimed by HAK. Finally, we discuss HAK's mode selection-criteria, based on correlation coefficients of trending series and find them invalid. Therefore, we perform a significance test based on a Monte Carlo technique and conclude that none of the modes identified by HAK are statistically significant.

  9. Nodal, paranodal and juxtaparanodal axonal proteins during demyelination and remyelination in multiple sclerosis.

    PubMed

    Coman, I; Aigrot, M S; Seilhean, D; Reynolds, R; Girault, J A; Zalc, B; Lubetzki, C

    2006-12-01

    Saltatory conduction in myelinated fibres depends on the specific molecular organization of highly specialized axonal domains at the node of Ranvier, the paranodal and the juxtaparanodal regions. Voltage-gated sodium channels (Na(v)) have been shown to be deployed along the naked demyelinated axon in experimental models of CNS demyelination and in multiple sclerosis lesions. Little is known about aggregation of nodal, paranodal and juxtaparanodal constituents during the repair process. We analysed by immunohistochemistry on free-floating sections from multiple sclerosis brains the expression and distribution of nodal (Na(v) channels), paranodal (paranodin/Caspr) and juxtaparanodal (K(v) channels and Caspr2) molecules in demyelinated and remyelinated lesions. Whereas in demyelinated lesions, paranodal and juxtaparanodal proteins are diffusely distributed on denuded axons, the distribution of Na(v) channels is heterogeneous, with a diffuse immunoreactivity but also few broad Na(v) channel aggregates in all demyelinated lesions. In contrast to the demyelinated plaques, all remyelinated lesions are characterized by the detection of aggregates of Na(v) channels, paranodin/Caspr, K(v) channels and Caspr2. Our data suggest that these aggregates precede remyelination, and that Na(v) channel aggregation is the initial event, followed by aggregation of paranodal and then juxtaparanodal axonal proteins. Remyelination takes place in multiple sclerosis tissue but myelin repair is often incomplete, and the reasons for this remyelination deficit are many. We suggest that a defect of Na(v) channel aggregation might be involved in the remyelination failure in demyelinated lesions with spared axons and oligodendroglial cells. PMID:16766541

  10. Myelin organization in the nodal, paranodal, and juxtaparanodal regions revealed by scanning x-ray microdiffraction.

    PubMed

    Inouye, Hideyo; Liu, Jiliang; Makowski, Lee; Palmisano, Marilena; Burghammer, Manfred; Riekel, Christian; Kirschner, Daniel A

    2014-01-01

    X-ray diffraction has provided extensive information about the arrangement of lipids and proteins in multilamellar myelin. This information has been limited to the abundant inter-nodal regions of the sheath because these regions dominate the scattering when x-ray beams of 100 µm diameter or more are used. Here, we used a 1 µm beam, raster-scanned across a single nerve fiber, to obtain detailed information about the molecular architecture in the nodal, paranodal, and juxtaparanodal regions. Orientation of the lamellar membrane stacks and membrane periodicity varied spatially. In the juxtaparanode-internode, 198-202 Å-period membrane arrays oriented normal to the nerve fiber axis predominated, whereas in the paranode-node, 205-208 Å-period arrays oriented along the fiber direction predominated. In parts of the sheath distal to the node, multiple sets of lamellar reflections were observed at angles to one another, suggesting that the myelin multilayers are deformed at the Schmidt-Lanterman incisures. The calculated electron density of myelin in the different regions exhibited membrane bilayer profiles with varied electron densities at the polar head groups, likely due to different amounts of major myelin proteins (P0 glycoprotein and myelin basic protein). Scattering from the center of the nerve fibers, where the x-rays are incident en face (perpendicular) to the membrane planes, provided information about the lateral distribution of protein. By underscoring the heterogeneity of membrane packing, microdiffraction analysis suggests a powerful new strategy for understanding the underlying molecular foundation of a broad spectrum of myelinopathies dependent on local specializations of myelin structure in both the PNS and CNS.

  11. miR-200c and GATA binding protein 4 regulate human embryonic stem cell renewal and differentiation.

    PubMed

    Huang, Hsiao-Ning; Chen, Shao-Yin; Hwang, Shiaw-Min; Yu, Ching-Chia; Su, Ming-Wei; Mai, Wei; Wang, Hsei-Wei; Cheng, Wei-Chung; Schuyler, Scott C; Ma, Nianhan; Lu, Frank Leigh; Lu, Jean

    2014-03-01

    Human embryonic stem cells (hESCs) are functionally unique for their self-renewal ability and pluripotency, but the molecular mechanisms giving rise to these properties are not fully understood. hESCs can differentiate into embryoid bodies (EBs) containing ectoderm, mesoderm, and endoderm. In the miR-200 family, miR-200c was especially enriched in undifferentiated hESCs and significantly downregulated in EBs. The knockdown of the miR-200c in hESCs downregulated Nanog expression, upregulated GATA binding protein 4 (GATA4) expression, and induced hESC apoptosis. The knockdown of GATA4 rescued hESC apoptosis induced by downregulation of miR-200c. miR-200c directly targeted the 3'-untranslated region of GATA4. Interestingly, the downregulation of GATA4 significantly inhibited EB formation in hESCs. Overexpression of miR-200c inhibited EB formation and repressed the expression of ectoderm, endoderm, and mesoderm markers, which could partially be rescued by ectopic expression of GATA4. Fibroblast growth factor (FGF) and activin A/nodal can sustain hESC renewal in the absence of feeder layer. Inhibition of transforming growth factor-β (TGF-β[Symbol: see text])/activin A/nodal signaling by SB431542 treatment downregulated the expression of miR-200c. Overexpression of miR-200c partially rescued the expression of Nanog/phospho-Smad2 that was downregulated by SB431542 treatment. Our observations have uncovered novel functions of miR-200c and GATA4 in regulating hESC renewal and differentiation.

  12. Quantum simulation of exotic PT -invariant topological nodal loop bands with ultracold atoms in an optical lattice

    NASA Astrophysics Data System (ADS)

    Zhang, Dan-Wei; Zhao, Y. X.; Liu, Rui-Bin; Xue, Zheng-Yuan; Zhu, Shi-Liang; Wang, Z. D.

    2016-04-01

    Since the well-known PT symmetry has its fundamental significance and implication in physics, where PT denotes a joint operation of space inversion P and time reversal T , it is important and intriguing to explore exotic PT -invariant topological metals and to physically realize them. Here we develop a theory for a different type of topological metals that are described by a two-band model of PT -invariant topological nodal loop states in a three-dimensional Brillouin zone, with the topological stability being revealed through the PT -symmetry-protected nontrivial Z2 topological charge even in the absence of both P and T symmetries. Moreover, the gapless boundary modes are demonstrated to originate from the nontrivial topological charge of the bulk nodal loop. Based on these exact results, we propose an experimental scheme to realize and to detect tunable PT -invariant topological nodal loop states with ultracold atoms in an optical lattice, in which atoms with two hyperfine spin states are loaded in a spin-dependent three-dimensional optical lattice and two pairs of Raman lasers are used to create out-of-plane spin-flip hopping with site-dependent phase. It is shown that such a realistic cold-atom setup can yield topological nodal loop states, having a tunable band-touching ring with the twofold degeneracy in the bulk spectrum and nontrivial surface states. The nodal loop states are actually protected by the combined PT symmetry and are characterized by a Z2-type invariant (or topological charge), i.e., a quantized Berry phase. Remarkably, we demonstrate with numerical simulations that (i) the characteristic nodal ring can be detected by measuring the atomic transfer fractions in a Bloch-Zener oscillation; (ii) the topological invariant may be measured based on the time-of-flight imaging; and (iii) the surface states may be probed through Bragg spectroscopy. The present proposal for realizing topological nodal loop states in cold-atom systems may provide a unique

  13. Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

    PubMed

    Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

    2011-01-01

    Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

  14. [Microglial cells and development of the embryonic central nervous system].

    PubMed

    Legendre, Pascal; Le Corronc, Hervé

    2014-02-01

    Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of microglia, their progenitor niche, the pattern of their invasion of the embryonic central nervous system and on interactions between embryonic microglia and their local environment during invasion. We describe microglial functions during development of embryonic neuronal networks, including their roles in neurogenesis, in angiogenesis and developmental cell death. These recent discoveries open a new field of research on the functions of neural-microglial interactions during the development of the embryonic central nervous system.

  15. Vascular endothelial growth factor C complements the ability of positron emission tomography to predict nodal disease in lung cancer

    PubMed Central

    Farjah, Farhood; Madtes, David K.; Wood, Douglas E.; Flum, David R.; Zadworny, Megan E.; Waworuntu, Rachel; Hwang, Billanna; Mulligan, Michael S.

    2016-01-01

    Objective Vascular endothelial growth factors (VEGFs) C and D are biologically rational markers of nodal disease that could improve the accuracy of lung cancer staging. We hypothesized that these biomarkers would improve the ability of positron emission tomography (PET) to predict nodal disease among patients with suspected or confirmed non–small cell lung cancer (NSCLC). Methods A cross-sectional study (2010–2013) was performed of patients prospectively enrolled in a lung nodule biorepository, staged by computed tomography (CT) and PET, and who underwent pathologic nodal evaluation. Enzyme-linked immunosorbent assay was used to measure biomarker levels in plasma from blood drawn before anesthesia. Likelihood ratio testing was used to compare the following logistic regression prediction models: ModelPET, ModelPET/VEGF-C, ModelPET/VEGF-D, and ModelPET/VEGF-C/VEGF-D. To account for 5 planned pairwise comparisons, P values<.01 were considered significant. Results Among 62 patients (median age, 67 years; 48% men; 87% white; and 84% NSCLC), 58% had fluorodeoxyglucose uptake in hilar and/or mediastinal lymph nodes. The prevalence of pathologically confirmed lymph node metastases was 40%. Comparisons of prediction models revealed the following: ModelPET/VEGF-C versus ModelPET (P = .0069), ModelPET/VEGF-D versus ModelPET (P = .1886), ModelPET/VEGF-C/VEGF-D versus ModelPET (P = .0146), ModelPET/VEGF-C/VEGF-D versus ModelPET/VEGF-C (P = .2818), and ModelPET/VEGF-C/VEGF-D versus ModelPET/VEGF-D (P = .0095). In ModelPET/VEGF-C, higher VEGF-C levels were associated with an increased risk of nodal disease (odds ratio, 2.96; 95% confidence interval, 1.26–6.90). Conclusions Plasma levels of VEGF-C complemented the ability of PET to predict nodal disease among patients with suspected or confirmed NSCLC. VEGF-D did not improve prediction. PMID:26320776

  16. On the correct representation of bending and axial deformation in the absolute nodal coordinate formulation with an elastic line approach

    NASA Astrophysics Data System (ADS)

    Gerstmayr, Johannes; Irschik, Hans

    2008-12-01

    In finite element methods that are based on position and slope coordinates, a representation of axial and bending deformation by means of an elastic line approach has become popular. Such beam and plate formulations based on the so-called absolute nodal coordinate formulation have not yet been verified sufficiently enough with respect to analytical results or classical nonlinear rod theories. Examining the existing planar absolute nodal coordinate element, which uses a curvature proportional bending strain expression, it turns out that the deformation does not fully agree with the solution of the geometrically exact theory and, even more serious, the normal force is incorrect. A correction based on the classical ideas of the extensible elastica and geometrically exact theories is applied and a consistent strain energy and bending moment relations are derived. The strain energy of the solid finite element formulation of the absolute nodal coordinate beam is based on the St. Venant-Kirchhoff material: therefore, the strain energy is derived for the latter case and compared to classical nonlinear rod theories. The error in the original absolute nodal coordinate formulation is documented by numerical examples. The numerical example of a large deformation cantilever beam shows that the normal force is incorrect when using the previous approach, while a perfect agreement between the absolute nodal coordinate formulation and the extensible elastica can be gained when applying the proposed modifications. The numerical examples show a very good agreement of reference analytical and numerical solutions with the solutions of the proposed beam formulation for the case of large deformation pre-curved static and dynamic problems, including buckling and eigenvalue analysis. The resulting beam formulation does not employ rotational degrees of freedom and therefore has advantages compared to classical beam elements regarding energy-momentum conservation.

  17. Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early stage cervical cancer

    PubMed Central

    Brooks, Rebecca; Kizer, Nora; Nguyen, Loan; Jaishuen, Atthapon; Wanat, Karolyn; Nugent, Elizabeth; Grigsby, Perry; Allsworth, Jenifer E.; Rader, Janet S.

    2009-01-01

    Objective Heritable polymorphisms modulate metastatic efficiency in cancer. Single nucleotide polymorphisms (SNPs) in MMP9 (rs17576) and SIPA1 (rs746429, rs931127) have been associated with nodal metastases in multiple cancers. We investigated the association of these SNPs with nodal metastases in early stage cervical cancer. Methods Consecutive patients with stage IB cervical cancer who underwent a pelvic lymph node (LN) dissection were included. Cases (≥ 1 positive LN, n=101) were compared with controls (negative LN pathology, n=273). Genotyping was performed on genomic DNA in the 3 SNPs using a Taqman assay, and correlated with clinical variables. Results The G allele at SIPA1 rs931127 was associated with an increased risk of nodal disease (OR 1.9, p=0.03), and approached significance at SIPA 1 rs746429 (OR 2.2, p=0.09) and MMP9 rs17576 (OR 1.5, 0.08). In patients with stage Ib1 lesions (n=304), the G allele at both SIPA1 SNPs were associated with LN metastases (rs746429 OR 10.1, p=0.01; rs931127 OR 2.4, p=0.01). In patients with no lymph vascular space invasion, SIPA1 SNPs were again associated with LN metastases, and all patients with nodal disease had at least one G allele at SIPA1 rs746429. Conclusions In this case control study, SNPs in SIPA1 varied statistically in cervical cancer patients with and without nodal metastases, and in MMP9 after controlling for stage and lymphvascular space invasion. Further work is needed to characterize inherited polymorphisms that provide a permissive background for the metastatic cascade. PMID:19906411

  18. The correction of pebble bed reactor nodal cross sections for the effects of leakage and depletion history

    NASA Astrophysics Data System (ADS)

    Hudson, Nathanael Harrison

    An accurate and computationally fast method to generate nodal cross sections for the Pebble Bed Reactor (PBR) was presented. In this method, named Spectral History Correction (SHC), a set of fine group microscopic cross section libraries, pre-computed at specified depletion and moderation states, was coupled with the nodal nuclide densities and group bucklings to compute the new fine group spectrum for each node. The relevant fine group cross-section library was then recollapsed to the local broad group cross-section structure with this new fine group spectrum. This library set was tracked in terms of fuel isotopic densities. Fine group modulation factors (to correct the homogeneous flux for heterogeneous effects) and fission spectra were also stored with the cross section library. As the PBR simulation converges to a steady state fuel cycle, the initial nodal cross section library becomes inaccurate due to the burnup of the fuel and the neutron leakage into and out of the node. Because of the recirculation of discharged fuel pebbles with fresh fuel pebbles, a node can consist of a collection of pebbles at various burnup stages. To account for the nodal burnup, the microscopic cross sections were combined with nodal averaged atom densities to approximate the fine group macroscopic cross-sections for that node. These constructed, homogeneous macroscopic cross sections within the node were used to calculate a numerical solution for the fine group spectrum with B1 theory. This new fine spectrum was used to collapse the pre-computed microscopic cross section library to the broad group structure employed by the fuel cycle code. This SHC technique was developed and practically implemented as a subroutine within the PBR fuel cycle code PEBBED. The SHC subroutine was called to recalculate the broad group cross sections during the code convergence. The result was a fast method that compared favorably to the benchmark scheme of cross section calculation with the lattice

  19. Diffusion-Weighted MRI for Nodal Staging of Head and Neck Squamous Cell Carcinoma: Impact on Radiotherapy Planning

    SciTech Connect

    Dirix, Piet; Vandecaveye, Vincent; De Keyzer, Frederik; Op de beeck, Katya; Poorten, Vincent Vander; Delaere, Pierre; Verbeken, Eric; Hermans, Robert; Nuyts, Sandra

    2010-03-01

    Purpose: To evaluate the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for nodal staging and its impact on radiotherapy (RT) planning. Methods and Materials: Twenty-two patients with locally advanced head and neck squamous cell carcinoma underwent contrast-enhanced computed tomography (CT), as well as MRI (with routine and DW sequences) prior to neck dissection. After topographic correlation, lymph nodes were evaluated microscopically with prekeratin immunostaining. Pathology results were correlated with imaging findings and an RT planning study was performed for these surgically treated patients. One set of target volumes was based on conventional imaging only, and another set was based on the corresponding DW-MRI images. A third reference set was contoured based solely on pathology results. Results: A sensitivity of 89% and a specificity of 97% per lymph node were found for DW-MRI. Nodal staging agreement between imaging and pathology was significantly stronger for DW-MRI (kappa = 0.97; 95% confidence interval [CI], 0.84-1.00) than for conventional imaging (kappa = 0.56; 95% CI, 0.16-0.96; p = 0.019, by McNemar's test). For both imaging modalities, the absolute differences between RT volumes and those obtained by pathology were calculated. Using an exact paired Wilcoxon test, the observed difference was significantly larger for conventional imaging than for DW-MRI for nodal gross tumor volume (p = 0.0013), as well as for nodal clinical target volume (p = 0.0415) delineation. Conclusions: These results suggest that DW-MRI is superior to conventional imaging for preradiotherapy nodal staging of head and neck squamous cell carcinoma, and provides a potential impact on organsparing and tumor control.

  20. Impact of FDG-PET/CT Imaging on Nodal Staging for Head-And-Neck Squamous Cell Carcinoma

    SciTech Connect

    Murakami, Ryuji . E-mail: murakami@kaiju.medic.kumamoto-u.ac.jp; Uozumi, Hideaki; Hirai, Toshinori; Nishimura, Ryuichi; Shiraishi, Shinya; Ota, Kazutoshi D.D.S.; Murakami, Daizo; Tomiguchi, Seiji; Oya, Natsuo; Katsuragawa, Shigehiko; Yamashita, Yasuyuki

    2007-06-01

    Purpose: To evaluate the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging on nodal staging for head-and-neck squamous cell carcinoma (SCC). Methods and Materials: The study population consisted of 23 patients with head-and-neck SCC who were evaluated with FDG-PET/CT and went on to neck dissection. Two observers consensually determined the lesion size and maximum standardized uptake value (SUV{sub max}) and compared the results with pathologic findings on nodal-level involvement. Two different observers (A and B) independently performed three protocols for clinical nodal staging. Methods 1, 2, and 3 were based on conventional modalities, additional visual information from FDG-PET/CT images, and FDG-PET/CT imaging alone with SUV data, respectively. Results: All primary tumors were visualized with FDG-PET/CT. Pathologically, 19 positive and 93 negative nodal levels were identified. The SUV{sub max} overlapped in negative and positive nodes <15 mm in diameter. According to receiver operating characteristics analysis, the size-based SUV{sub max} cutoff values were 1.9, 2.5, and 3.0 for lymph nodes <10 mm, 10-15 mm, and >15 mm, respectively. These cutoff values yielded 79% sensitivity and 99% specificity for nodal-level staging. For Observer A, the sensitivity and specificity in Methods 1, 2, and 3 were 68% and 94%, 68% and 99%, and 84% and 99%, respectively, and Method 3 yielded significantly higher accuracy than Method 1 (p = 0.0269). For Observer B, Method 3 yielded the highest sensitivity (84%) and specificity (99%); however, the difference among the three protocols was not statistically significant. Conclusion: Imaging with FDG-PET/CT with size-based SUV{sub max} cutoff values is an important modality for radiation therapy planning.

  1. Nodal endoplasmic reticulum, a specialized form of endoplasmic reticulum found in gravity-sensing root tip columella cells

    NASA Technical Reports Server (NTRS)

    Zheng, H. Q.; Staehelin, L. A.

    2001-01-01

    The endoplasmic reticulum (ER) of columella root cap cells has been postulated to play a role in gravity sensing. We have re-examined the ultrastructure of columella cells in tobacco (Nicotiana tabacum) root tips preserved by high-pressure freezing/freeze-substitution techniques to gain more precise information about the organization of the ER in such cells. The most notable findings are: the identification of a specialized form of ER, termed "nodal ER," which is found exclusively in columella cells; the demonstration that the bulk of the ER is organized in the form of a tubular network that is confined to a peripheral layer under the plasma membrane; and the discovery that this ER-rich peripheral region excludes Golgi stacks, vacuoles, and amyloplasts but not mitochondria. Nodal ER domains consist of an approximately 100-nm-diameter central rod composed of oblong subunits to which usually seven sheets of rough ER are attached along their margins. These domains form patches at the interface between the peripheral ER network and the ER-free central region of the cells, and they occupy defined positions within central and flanking columella cells. Over one-half of the nodal ER domains are located along the outer tangential walls of the flanking cells. Cytochalasin D and latrunculin A cause an increase in size and a decrease in numbers of nodal ER domains. We postulate that the nodal ER membranes locally modulate the gravisensing signals produced by the sedimenting amyloplasts, and that the confinement of all ER membranes to the cell periphery serves to enhance the sedimentability of the amyloplasts in the central region of columella cells.

  2. Incidental Nodal Lymphangioleiomyomatosis Is Not a Harbinger of Pulmonary Lymphangioleiomyomatosis: A Study of 19 Cases with Evaluation of Diagnostic Immunohistochemistry

    PubMed Central

    Schoolmeester, J. Kenneth; Park, Kay J.

    2016-01-01

    Lymphangioleiomyomatosis (LAM) is a proliferation of perivascular epithelioid cells typically affecting the lung as a low grade, destructive and progressive disease, but may also be found in lymph nodes and other organs. LAM is sometimes seen as an incidental finding in lymph node dissections performed for staging of gynecologic tumors. To our knowledge, no study has investigated the clinical significance of incidental nodal LAM in relation to subsequent development of pulmonary LAM. We identified 19 patients from our institution with LAM in lymph nodes. Follow up was available for 100% of patients and ranged from 3 to 123 months (mean 33.8 months). All were women and ages ranged from 35 to 71 years (mean 56.3). None had a history of tuberous sclerosis, renal angiomyolipoma or pulmonary LAM. LAM involvement spanned 1 to 6 nodes (mean 2) ranging from 1 to 100% of the total excised lymph nodes. The single largest focus of nodal LAM ranged from 1 to 9 mm (mean 4.3) in 18 patients without evidence of persistent or recurrent nodal LAM. In the one patient with persistent local nodal LAM, the greatest diameter was 25 mm. Affected lymph node sites were regional pelvic and retroperitoneal chains routinely sampled in staging operations. An immunohisotchemical panel of HMB45, A103 and β-catenin was evaluated in 18 cases. HMB45 showed strong, but usually focal staining in every case compared to A103 which was very focally expressed (39%) or negative. β-catenin showed strong, diffuse cytoplasmic and membranous (nonnuclear) reactivity in 100% of cases. At last clinic visit, all 19 patients had no manifestations of pulmonary LAM. In an absence of signs of symptoms of extranodal LAM, patients with incidentally discovered nodal LAM smaller than 10 mm are not at risk for developing pulmonary LAM. PMID:26135558

  3. Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest

    PubMed Central

    Yan, Shao-Fei; Liu, Xin-Yan; Cheng, Yun-Fei; Li, Zhi-Yi; Ou, Jie; Wang, Wei; Li, Feng-Qin

    2016-01-01

    Background: Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy. The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear. This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest. Methods: Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group). Results: Intrauterine bacterial infection was discovered in both groups. The infection rate was 24.44% (11/45) in the early embryonic developmental arrest group and 9.09% (3/33) in the artificial abortion group. Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% (6/45), and none was detected in the artificial abortion group. M. luteus infection was significantly different between the groups (P < 0.05 as shown by Fisher's exact test). In addition, no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest. Conclusions: M. luteus infection is related to early embryonic developmental arrest and might be one of its causative factors. PMID:27270541

  4. BMP Signaling Dynamics in Embryonic Orofacial Tissue

    PubMed Central

    MUKHOPADHYAY, PARTHA; WEBB, CYNTHIA L.; WARNER, DENNIS R.; GREENE, ROBERT M.; PISANO, M. MICHELE

    2009-01-01

    The bone morphogenetic protein (BMP) family represents a class of signaling molecules, that plays key roles in morphogenesis, cell proliferation, survival and differentiation during normal development. Members of this family are essential for the development of the mammalian orofacial region where they regulate cell proliferation, extracellular matrix synthesis, and cellular differentiation. Perturbation of any of these processes results in orofacial clefting. Embryonic orofacial tissue expresses BMP mRNAs, their cognate proteins, and BMP-specific receptors in unique temporo-spatial patterns, suggesting functional roles in orofacial development. However, specific genes that function as downstream mediators of BMP action during orofacial ontogenesis have not been well defined. In the current study, elements of the Smad component of the BMP intracellular signaling system were identified and characterized in embryonic orofacial tissue and functional activation of the Smad pathway by BMP2 and BMP4 was demonstrated. BMP2 and BMP4-initiated Smad signaling in cells derived from embryonic orofacial tissue was found to result in: (1) phosphorylation of Smads 1 and 5; (2) nuclear translocation of Smads 1, 4, and 5; (3) binding of Smads 1, 4, and 5 to a consensus Smad binding element (SBE)-containing oligonucleotide; (4) transactivation of transfected reporter constructs, containing BMP-inducible Smad response elements; and (5) increased expression at transcriptional as well as translational levels of Id3 (endogenous gene containing BMP receptor-specific Smad response elements). Collectively, these data document the existence of a functional Smad-mediated BMP signaling system in cells of the developing murine orofacial region. PMID:18446813

  5. Molecular characterization of Rhodnius prolixus' embryonic cuticle.

    PubMed

    Souza-Ferreira, Paula S; Moreira, Mônica F; Atella, Geórgia C; Oliveira-Carvalho, Ana Lúcia; Eizemberg, Roberto; Majerowicz, David; Melo, Ana C A; Zingali, Russolina B; Masuda, Hatisaburo

    2014-08-01

    The embryonic cuticle (EC) of Rhodnius prolixus envelopes the entire body of the embryo during hatching and provides physical protection, allowing the embryo to pass through a narrow chorionic border. Most of the knowledge about the EC of insects is derived from studies on ultrastructure and secretion processes during embryonic development, and little is known about the molecular composition of this structure. We performed a comprehensive molecular characterization of the major components extracted from the EC of R. prolixus, and we discuss the role of the different molecules that were identified during the eclosion process. The results showed that, similar to the post-embryonic cuticles of insects, the EC of R. prolixus is primarily composed of carbohydrates (57%), lipids (19%), and proteins (8%). Considering only the carbohydrates, chitin is by far the major component (approximately 70%), and it is found primarily along the body of the EC. It is scarce or absent in its prolongations, which are composed of glycosaminoglycans. In addition to chitin, we also identified amino (15%), neutral (12%) and acidic (3%) carbohydrates in the EC of R. prolixus. In addition carbohydrates, we also identified neutral lipids (64.12%) and phospholipids (35.88%). Proteomic analysis detected 68 proteins (55 were identified and 13 are hypothetical proteins) using the sequences in the R. prolixus genome (http://www.vectorbase.org). Among these proteins, 8 out of 15 are associated with cuticle metabolism. These proteins are unequivocally cuticle proteins, and they have been described in other insects. Approximately 35% of the total proteins identified were classified as having a structural function. Chitin-binding protein, amino peptidase, amino acid oxidase, oxidoreductase, catalase and peroxidase are all proteins associated with cuticle metabolism. Proteins known to be cuticle constituents may be related to the function of the EC in assisting the insect during eclosion. To our

  6. Embryonic skulls of titanosaur sauropod dinosaurs.

    PubMed

    Chiappe, L M; Salgado, L; Coria, R A

    2001-09-28

    Little is known about the cranial anatomy of the taxonomically diverse and geographically widespread titanosaurs, a paucity that has hindered inferences about the genealogical history and evolutionary development of the latest sauropod dinosaurs. Newly discovered fossil eggs containing embryonic remains from the Late Cretaceous of Argentina provide the first articulated skulls of titanosaur dinosaurs. The nearly complete fetal skulls shed light on the evolution of some of the most notable cranial features of sauropod dinosaurs, including the retraction of the external nares, the forward rotation of the braincase, and the abbreviation of the infraorbital region. PMID:11577234

  7. Automated maintenance of embryonic stem cell cultures.

    PubMed

    Terstegge, Stefanie; Laufenberg, Iris; Pochert, Jörg; Schenk, Sabine; Itskovitz-Eldor, Joseph; Endl, Elmar; Brüstle, Oliver

    2007-01-01

    Embryonic stem cell (ESC) technology provides attractive perspectives for generating unlimited numbers of somatic cells for disease modeling and compound screening. A key prerequisite for these industrial applications are standardized and automated systems suitable for stem cell processing. Here we demonstrate that mouse and human ESC propagated by automated culture maintain their mean specific growth rates, their capacity for multi-germlayer differentiation, and the expression of the pluripotency-associated markers SSEA-1/Oct-4 and Tra-1-60/Tra-1-81/Oct-4, respectively. The feasibility of ESC culture automation may greatly facilitate the use of this versatile cell source for a variety of biomedical applications.

  8. Dynamic Proteomic Profiling of Extra-Embryonic Endoderm Differentiation in Mouse Embryonic Stem Cells.

    PubMed

    Mulvey, Claire M; Schröter, Christian; Gatto, Laurent; Dikicioglu, Duygu; Fidaner, Isik Baris; Christoforou, Andy; Deery, Michael J; Cho, Lily T Y; Niakan, Kathy K; Martinez-Arias, Alfonso; Lilley, Kathryn S

    2015-09-01

    During mammalian preimplantation development, the cells of the blastocyst's inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra-embryonic tissues, respectively. Extra-embryonic endoderm (XEN) differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here, we use this GATA-inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo-derived XEN cells. Using mass spectrometry-based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and XEN differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin-modifying enzymes, the reorganization of membrane trafficking machinery, and the breakdown of cell-cell adhesion are successive steps of the extra-embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time-resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes.

  9. Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: What is the role of elective neck irradiation?

    SciTech Connect

    Chen, Allen M. . E-mail: allenmchen@yahoo.com; Garcia, Joaquin; Lee, Nancy Y.; Bucci, M. Kara; Eisele, David W.

    2007-03-15

    Purpose: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). Methods and Materials: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinoma (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3-267 months). Results: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. Conclusion: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.

  10. Role of Ultrasonography of Regional Nodal Basins in Staging Triple-Negative Breast Cancer and Implications For Local-Regional Treatment

    SciTech Connect

    Shaitelman, Simona F.; Tereffe, Welela; Dogan, Basak E.; Hess, Kenneth R.; Caudle, Abigail S.; Valero, Vicente; Stauder, Michael C.; Krishnamurthy, Savitri; Candelaria, Rosalind P.; Strom, Eric A.; Woodward, Wendy A.; Hunt, Kelly K.; Buchholz, Thomas A.; Whitman, Gary J.

    2015-09-01

    Purpose: We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. Methods and Materials: We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients' disease with and without ultrasonography of the regional nodal basins were compared using the Pearson χ{sup 2} test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. Results: A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P<.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P<.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P<.0001). Conclusions: Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning.

  11. Mechanical signaling coordinates the embryonic heart

    NASA Astrophysics Data System (ADS)

    Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea

    The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.

  12. Proteome analysis of chick embryonic cerebrospinal fluid.

    PubMed

    Parada, Carolina; Gato, Angel; Aparicio, Mariano; Bueno, David

    2006-01-01

    During early stages of embryo development, the brain cavity is filled with embryonic cerebrospinal fluid (E-CSF), a complex fluid containing different protein fractions that contributes to the regulation of the survival, proliferation and neurogenesis of the neuroectodermal stem cells. Using 2-DE, protein sequencing and database searches, we identified and analyzed the proteome of the E-CSF from chick embryos (Gallus gallus). We identified 26 different gene products, including proteins related to the extracellular matrix, proteins associated with the regulation of osmotic pressure and metal transport, proteins related to cell survival, MAP kinase activators, proteins involved in the transport of retinol and vitamin D, antioxidant and antimicrobial proteins, intracellular proteins and some unknown proteins. Most of these gene products are involved in the regulation of developmental processes during embryogenesis in systems other than E-CSF. Interestingly, 14 of them are also present in adult human CSF proteome, and it has been reported that they are altered in the CSF of patients suffering neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis is a key contribution to the general understanding of CNS development, and may also contribute to greater knowledge of these human diseases. PMID:16287170

  13. Pluripotent states of human embryonic stem cells.

    PubMed

    Chen, Yifei; Lai, Dongmei

    2015-02-01

    Since human embryonic stem cells (hESCs) were first isolated and successfully cultured in vitro, the pluripotent potential of hESCs has been underestimated. The pluripotency of mouse embryonic stem cells (mESCs) can be categorized as naïve and primed, depending on their corresponding in vivo developing phases. mESC morphology differs at distinct pluripotent states, which differ in signaling dependence, gene expression, epigenetic features, and developmental potential. hESCs resemble mouse stem cells at primed pluripotency, and consequently are believed to correspond to a later developmental stage in vivo than mESCs. Nevertheless, recent studies indicate that a naïve state of pluripotency may exist in hESCs, and the pluripotency of hESCs also can be enhanced by genetic modification or optimized culture systems. These findings provide novel insight into the properties and differentiation potential of hESCs. Here, we review the recent advances in characterization of ESC states and investigate the mechanisms regulating hESC pluripotency. PMID:25393391

  14. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

    PubMed Central

    Maurer, Maria; Ebner, Thomas; Puchner, Manuela; Mayer, Richard Bernhard; Shebl, Omar; Oppelt, Peter; Duba, Hans-Christoph

    2015-01-01

    Background Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF) technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH) with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting. PMID:26644858

  15. Disseminated Cerebrospinal Embryonal Tumor in the Adult

    PubMed Central

    Armocida, Daniele; Caporlingua, Federico; Lapadula, Gennaro; Elefante, Grazia Maria; Antonelli, Manila; Salvati, Maurizio

    2016-01-01

    Introduction. According to the 2016 World Health Organization classification of Tumors of the Central Nervous System, the term Primitive Neuroectodermal Tumor has been replaced by the term Embryonal Tumor (ET). We present a case of disseminated cerebrospinal ET presenting in an adult patient. Illustrative Case. A 49-year-old male presenting with low back pain, dysuria, and hypoesthesia of the lower extremities referred to our emergency department. Brain and whole spine contrast-enhanced MRI documented a diffusively disseminated heterogeneous neoplasm with intradural extra- and intramedullary involvement of the cervicothoracic tract and cauda equina. A primary biopsy of the lumbosacral localization was performed through L5 bilateral laminectomy. Histologic diagnosis was Embryonal Tumor Not Otherwise Specified. The patient underwent chemotherapy with postoperative adjuvant alternating Vincristine-Doxorubicin-Ifosfamide (VAI) and Ifosfamide-Etoposide (IE). Discussion. Spinal ETs are exceedingly rare especially when presenting in the adult patient. Neurosurgical and oncologic management is still unclear. When feasible, surgical removal should always be performed to obtain a histologic diagnosis. Postoperative adjuvant therapy might entail both chemo- and radiotherapy; however a consensus on this matter is still lacking.

  16. 4D embryonic cardiography using gated optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Jenkins, M. W.; Rothenberg, F.; Roy, D.; Nikolski, V. P.; Hu, Z.; Watanabe, M.; Wilson, D. L.; Efimov, I. R.; Rollins, A. M.

    2006-01-01

    Simultaneous imaging of very early embryonic heart structure and function has technical limitations of spatial and temporal resolution. We have developed a gated technique using optical coherence tomography (OCT) that can rapidly image beating embryonic hearts in four-dimensions (4D), at high spatial resolution (10-15 μm), and with a depth penetration of 1.5 - 2.0 mm that is suitable for the study of early embryonic hearts. We acquired data from paced, excised, embryonic chicken and mouse hearts using gated sampling and employed image processing techniques to visualize the hearts in 4D and measure physiologic parameters such as cardiac volume, ejection fraction, and wall thickness. This technique is being developed to longitudinally investigate the physiology of intact embryonic hearts and events that lead to congenital heart defects.

  17. Primed Pluripotent Cell Lines Derived from Various Embryonic Origins and Somatic Cells in Pig

    PubMed Central

    Park, Jin-Kyu; Kim, Hye-Sun; Uh, Kyung-Jun; Choi, Kwang-Hwan; Kim, Hyeong-Min; Lee, Taeheon; Yang, Byung-Chul; Kim, Hyun-Jong; Ka, Hak-Hyun; Kim, Heebal; Lee, Chang-Kyu

    2013-01-01

    Since pluripotent embryonic stem cell (ESC) lines were first derived from the mouse, tremendous efforts have been made to establish ESC lines in several domestic species including the pig; however, authentic porcine ESCs have not yet been established. It has proven difficult to maintain an ESC-like state in pluripotent porcine cell lines due to the frequent occurrence of spontaneous differentiation into an epiblast stem cell (EpiSC)-like state during culture. We have been able to derive EpiSC-like porcine ESC (pESC) lines from blastocyst stage porcine embryos of various origins, including in vitro fertilized (IVF), in vivo derived, IVF aggregated, and parthenogenetic embryos. In addition, we have generated induced pluripotent stem cells (piPSCs) via plasmid transfection of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) into porcine fibroblast cells. In this study, we analyzed characteristics such as marker expression, pluripotency and the X chromosome inactivation status in female of our EpiSC-like pESC lines along with our piPSC line. Our results show that these cell lines demonstrate the expression of genes associated with the Activin/Nodal and FGF2 pathways along with the expression of pluripotent markers Oct4, Sox2, Nanog, SSEA4, TRA 1–60 and TRA 1–81. Furthermore all of these cell lines showed in vitro differentiation potential, the X chromosome inactivation in female and a normal karyotype. Here we suggest that the porcine species undergoes reprogramming into a primed state during the establishment of pluripotent stem cell lines. PMID:23326334

  18. Transplantation of Neural Stem Cells Clonally Derived from Embryonic Stem Cells Promotes Recovery After Murine Spinal Cord Injury

    PubMed Central

    Salewski, Ryan P.; Mitchell, Robert A.; Shen, Carl

    2015-01-01

    The pathology of spinal cord injury (SCI) makes it appropriate for cell-based therapies. Treatments using neural stem cells (NSCs) in animal models of SCI have shown positive outcomes, although uncertainty remains regarding the optimal cell source. Pluripotent cell sources such as embryonic stem cells (ESCs) provide a limitless supply of therapeutic cells. NSCs derived using embryoid bodies (EB) from ESCs have shown tumorigenic potential. Clonal neurosphere generation is an alternative method to generate safer and more clinically relevant NSCs without the use of an EB stage for use in cell-based therapies. We generated clonally derived definitive NSCs (dNSCs) from ESC. These cells were transplanted into a mouse thoracic SCI model. Embryonic stem cell-derived definitive neural stem cell (ES-dNSC)-transplanted mice were compared with controls using behavioral measures and histopathological analysis of tissue. In addition, the role of remyelination in injury recovery was investigated using transmission electron microscopy. The SCI group that received ES-dNSC transplantation showed significant improvements in locomotor function compared with controls in open field and gait analysis. The cell treatment group had a significant enhancement of spared neural tissue. Immunohistological assessments showed that dNSCs differentiated primarily to oligodendrocytes. These cells were shown to express myelin basic protein, associate with axons, and support nodal architecture as well as display proper compact, multilayer myelination in electron microscopic analysis. This study provides strong evidence that dNSCs clonally derived from pluripotent cells using the default pathway of neuralization improve motor function after SCI and enhance sparing of neural tissue, while remaining safe and clinically relevant. PMID:25119334

  19. Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells

    PubMed Central

    Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

    2014-01-01

    Summary Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. PMID:24936448

  20. Nodal-line pairing with 1D-3D coupled Fermi surfaces: A model motivated by Cr-based superconductors

    NASA Astrophysics Data System (ADS)

    Wachtel, Gideon; Kim, Yong Baek

    2016-09-01

    Motivated by the recent discovery of a new family of chromium-based superconductors, we consider a two-band model, where a band of electrons dispersing only in one direction interacts with a band of electrons dispersing in all three directions. Strong 2 kf density fluctuations in the one-dimensional band induces attractive interactions between the three-dimensional electrons, which, in turn, makes the system superconducting. Solving the associated Eliashberg equations, we obtain a gap function which is peaked at the "poles" of the three-dimensional Fermi sphere, and decreases towards the "equator." When strong enough local repulsion is included, the gap actually changes sign around the equator and nodal rings are formed. These nodal rings manifest themselves in several experimentally observable quantities, some of which resemble unconventional observations in the newly discovered superconductors which motivated this work.