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Sample records for hedgehog ligand sequestration

  1. Dispatched and Scube Mediate the Efficient Secretion of the Cholesterol-Modified Hedgehog Ligand

    OpenAIRE

    Hanna Tukachinsky; Ryan P. Kuzmickas; Cindy Y. Jao; Jing Liu; Adrian Salic

    2012-01-01

    The Hedgehog signaling pathway plays critical roles in metazoan development and in cancer. How the Hedgehog ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hedgehog ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, one mediated by the membrane protein Dispatched and the other by a...

  2. Sex and hedgehog: roles of genes in the hedgehog signaling pathway in mammalian sexual differentiation.

    Science.gov (United States)

    Franco, Heather L; Yao, Humphrey H-C

    2012-01-01

    The chromosome status of the mammalian embryo initiates a multistage process of sexual development in which the bipotential reproductive system establishes itself as either male or female. These events are governed by intricate cell-cell and interorgan communication that is regulated by multiple signaling pathways. The hedgehog signaling pathway was originally identified for its key role in the development of Drosophila, but is now recognized as a critical developmental regulator in many species, including humans. In addition to its developmental roles, the hedgehog signaling pathway also modulates adult organ function, and misregulation of this pathway often leads to diseases, such as cancer. The hedgehog signaling pathway acts through its morphogenetic ligands that signal from ligand-producing cells to target cells over a specified distance. The target cells then respond in a graded manner based on the concentration of the ligands that they are exposed to. Through this unique mechanism of action, the hedgehog signaling pathway elicits cell fate determination, epithelial-mesenchymal interactions, and cellular homeostasis. Here, we review current findings on the roles of hedgehog signaling in the sexually dimorphic development of the reproductive organs with an emphasis on mammals and comparative evidence in other species.

  3. Dispatched and Scube Mediate the Efficient Secretion of the Cholesterol-Modified Hedgehog Ligand

    Directory of Open Access Journals (Sweden)

    Hanna Tukachinsky

    2012-08-01

    Full Text Available The Hedgehog (Hh signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified Hh ligand.

  4. Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog.

    Science.gov (United States)

    Tukachinsky, Hanna; Petrov, Kostadin; Watanabe, Miyako; Salic, Adrian

    2016-10-04

    The Hedgehog cell-cell signaling pathway is crucial for animal development, and its misregulation is implicated in numerous birth defects and cancers. In unstimulated cells, pathway activity is inhibited by the tumor suppressor membrane protein, Patched. Hedgehog signaling is triggered by the secreted Hedgehog ligand, which binds and inhibits Patched, thus setting in motion the downstream events in signal transduction. Despite its critical importance, the mechanism by which Hedgehog antagonizes Patched has remained unknown. Here, we show that vertebrate Patched1 inhibition is caused by direct, palmitate-dependent interaction with the Sonic Hedgehog ligand. We find that a short palmitoylated N-terminal fragment of Sonic Hedgehog binds Patched1 and, strikingly, is sufficient to inhibit it and to activate signaling. The rest of Sonic Hedgehog confers high-affinity Patched1 binding and internalization through a distinct binding site, but, surprisingly, it is not absolutely required for signaling. The palmitate-dependent interaction with Patched1 is specifically impaired in a Sonic Hedgehog mutant causing human holoprosencephaly, the most frequent congenital brain malformation, explaining its drastically reduced potency. The palmitate-dependent interaction is also abolished in constitutively inhibited Patched1 point mutants causing the Gorlin cancer syndrome, suggesting that they might adopt a conformation distinct from the wild type. Our data demonstrate that Sonic Hedgehog signals via the palmitate-dependent arm of a two-pronged contact with Patched1. Furthermore, our results suggest that, during Hedgehog signaling, ligand binding inhibits Patched by trapping it in an inactive conformation, a mechanism that explains the dramatically reduced activity of oncogenic Patched1 mutants.

  5. Dispatched and scube mediate the efficient secretion of the cholesterol-modified hedgehog ligand.

    Science.gov (United States)

    Tukachinsky, Hanna; Kuzmickas, Ryan P; Jao, Cindy Y; Liu, Jing; Salic, Adrian

    2012-08-30

    The Hedgehog (Hh) signaling pathway plays critical roles in metazoan development and in cancer. How the Hh ligand is secreted and spreads to distant cells is unclear, given its covalent modification with a hydrophobic cholesterol molecule, which makes it stick to membranes. We demonstrate that Hh ligand secretion from vertebrate cells is accomplished via two distinct and synergistic cholesterol-dependent binding events, mediated by two proteins that are essential for vertebrate Hh signaling: the membrane protein Dispatched (Disp) and a member of the Scube family of secreted proteins. Cholesterol modification is sufficient for a heterologous protein to interact with Scube and to be secreted in a Scube-dependent manner. Disp and Scube recognize different structural aspects of cholesterol similarly to how Niemann-Pick disease proteins 1 and 2 interact with cholesterol, suggesting a hand-off mechanism for transferring Hh from Disp to Scube. Thus, Disp and Scube cooperate to dramatically enhance the secretion and solubility of the cholesterol-modified Hh ligand. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Hedgehog signaling and therapeutics in pancreatic cancer.

    LENUS (Irish Health Repository)

    Kelleher, Fergal C

    2012-02-01

    OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

  7. A review of hedgehog signaling in cranial bone development

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    Angel ePan

    2013-04-01

    Full Text Available During craniofacial development, the Hedgehog (HH signaling pathway is essential for mesodermal tissue patterning and differentiation. The Hedgehog family consists of three protein ligands: Sonic Hedgehog (SHH, Indian Hedgehog (IHH, and Desert Hedgehog (DHH, of which two are expressed in the craniofacial complex (IHH and SHH. Dysregulations in HH signaling are well documented to result in a wide range of craniofacial abnormalities, including holoprosencephaly, hypotelorism, and cleft lip/palate. Furthermore, mutations in HH effectors, co-receptors, and ciliary proteins result in skeletal and craniofacial deformities. Cranial suture morphogenesis is a delicate developmental process that requires control of cell commitment, proliferation and differentiation. This review focuses on both what is known and what remains unknown regarding HH signaling in cranial suture morphogenesis and intramembranous ossification. As demonstrated from murine studies, expression of both SHH and IHH is critical to the formation and fusion of the cranial sutures and calvarial ossification. SHH expression has been observed in the cranial suture mesenchyme and its precise function is not fully defined, although some postulate SHH to delay cranial suture fusion. IHH expression is mainly found on the osteogenic fronts of the calvarial bones, and functions to induce cell proliferation and differentiation. Unfortunately, neonatal lethality of deficient mice precludes a detailed examination of their postnatal calvarial phenotype. In summary, a number of basic questions are yet to be answered regarding domains of expression, developmental role, and functional overlap of HH morphogens in the calvaria. Nevertheless, SHH and IHH ligands are integral to cranial suture development and regulation of calvarial ossification. When HH signaling goes awry, the resultant suite of morphologic abnormalities highlights the important roles of HH signaling in cranial development.

  8. The Binding Mode of the Sonic Hedgehog Inhibitor Robotnikinin, a Combined Docking and QM/MM MD Study

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    Manuel Hitzenberger

    2017-10-01

    Full Text Available Erroneous activation of the Hedgehog pathway has been linked to a great amount of cancerous diseases and therefore a large number of studies aiming at its inhibition have been carried out. One leverage point for novel therapeutic strategies targeting the proteins involved, is the prevention of complex formation between the extracellular signaling protein Sonic Hedgehog and the transmembrane protein Patched 1. In 2009 robotnikinin, a small molecule capable of binding to and inhibiting the activity of Sonic Hedgehog has been identified, however in the absence of X-ray structures of the Sonic Hedgehog-robotnikinin complex, the binding mode of this inhibitor remains unknown. In order to aid with the identification of novel Sonic Hedgehog inhibitors, the presented investigation elucidates the binding mode of robotnikinin by performing an extensive docking study, including subsequent molecular mechanical as well as quantum mechanical/molecular mechanical molecular dynamics simulations. The attained configurations enabled the identification of a number of key protein-ligand interactions, aiding complex formation and providing stabilizing contributions to the binding of the ligand. The predicted structure of the Sonic Hedgehog-robotnikinin complex is provided via a PDB file as Supplementary Material and can be used for further reference.

  9. Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response.

    Science.gov (United States)

    Westendorp, B Florien; Büller, Nikè V J A; Karpus, Olga N; van Dop, Willemijn A; Koster, Jan; Versteeg, Rogier; Koelink, Pim J; Snel, Clinton Y; Meisner, Sander; Roelofs, Joris J T H; Uhmann, Anja; Ver Loren van Themaat, Emiel; Heijmans, Jarom; Hahn, Heidi; Muncan, Vanesa; Wildenberg, Manon E; van den Brink, Gijs R

    2018-01-01

    Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation. Hedgehog activity was modulated genetically in both cell type-specific and body-wide models and the resulting animals were analyzed for gene expression profiles and sensitivity for dextran sodium sulfate (DSS) colitis. To characterize the Hedgehog target cell, Gli1-CreERT2-Rosa26-ZsGreen animals were generated, which express ZsGreen in all Hedgehog-responsive cells. These cells were characterized using flow cytometry and immunofluorescence. Loss of Indian Hedgehog from the intestinal epithelium resulted in a rapid increase in expression of inflammation-related genes, accompanied by increased influx of immune cells. Animals with epithelium-specific deletion of Ihh or lacking the Hedgehog receptor Smoothened from Hedgehog target cells were more sensitive to DSS colitis. In contrast, specific deletion of Smoothened in the myeloid compartment did not alter the response to DSS. This suggests that Hedgehog signaling does not repress intestinal immunity through an effect on myeloid cells. Indeed, we found that Hedgehog-responsive cells expressed gp38, smooth muscle actin, and desmin, indicating a fibroblastic nature. Ihh signaling inhibited expression of C-X-C motif chemokine ligand 12 (CXCL12) in fibroblasts in vitro and in vivo, thereby impairing the recruitment of immune cells. We show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast

  10. Hedgehog Protein Cholesterolysis: A New Therapeutic Target for Advanced Prostate Cancer

    Science.gov (United States)

    2016-10-01

    cholesterolysis, the oncogenic Hh polypeptide is generated through a peptide cleavage reaction involving cholesterol. Cholesterolysis represents an...ligand, HhN, is released from this precursor by peptide bond cholesterolysis, a cleavage/lipidation event unique to the Hh family[4] (Figure 1A...substrate activity of A and G through sec- ondary assays involving a chimeric Hh precursor, where the human sonic hedgehog ligand (20 kDa) is fused to the

  11. Hedgehog hives.

    Science.gov (United States)

    Fairley, J A; Suchniak, J; Paller, A S

    1999-05-01

    Hedgehogs are increasingly popular pets in the United States and Europe. A number of infections may be acquired from these animals, and hedgehogs are possible hosts of parasites. However, to our knowledge there arc no previous reports of urticarial reactions to hedgehogs. We describe 3 patients who developed an acute, transient, urticarial reaction after contact with the extended spines of pet hedgehogs. One patient also developed a more prolonged reaction at the site of contact. Interestingly, all 3 patients had documented allergies to cats and/or dogs. The results of prick testing in 1 patient to an extract of hedgehog dander produced an immediate wheal-and-flare reaction. A variety of dermatologic disorders may be seen in handlers of hedgehogs. Due to the increasing popularity of these animals as pets, it is likely that these reactions will be noted more frequently by dermatologists. The presence of allergies to other pets may be predictive of hedgehog hives and further investigation of the cross reaction of various animal antigens may clarify this relationship.

  12. Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

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    Alexandre N Ermilov

    2016-11-01

    Full Text Available For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings

  13. Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI Signaling.

    Science.gov (United States)

    Ermilov, Alexandre N; Kumari, Archana; Li, Libo; Joiner, Ariell M; Grachtchouk, Marina A; Allen, Benjamin L; Dlugosz, Andrzej A; Mistretta, Charlotte M

    2016-11-01

    For homeostasis, lingual taste papilla organs require regulation of epithelial cell survival and renewal, with sustained innervation and stromal interactions. To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a panel of conditional mouse models to manipulate GLI activity within epithelial cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression rapidly led to taste bud loss, papilla disruption, and decreased proliferation in domains of papilla epithelium that contribute to taste cells. Hedgehog responding cells were eliminated from the epithelium but retained in the papilla stromal core. Despite papilla disruption and loss of taste buds that are a major source of Hedgehog ligand, innervation to taste papillae was maintained, and not misdirected, even after prolonged GLI blockade. Further, vimentin-positive fibroblasts remained in the papilla core. However, retained innervation and stromal cells were not sufficient to maintain taste bud cells in the context of compromised epithelial Hedgehog signaling. Importantly taste organ disruption after GLI blockade was reversible in papillae that retained some taste bud cell remnants where reactivation of Hedgehog signaling led to regeneration of papilla epithelium and taste buds. Therefore, taste bud progenitors were either retained during epithelial GLI blockade or readily repopulated during recovery, and were poised to regenerate taste buds once Hedgehog signaling was restored, with innervation and papilla connective tissue elements in place. Our data argue that Hedgehog signaling is essential for adult tongue tissue maintenance and that taste papilla epithelial cells represent the key targets for physiologic Hedgehog-dependent regulation of taste organ homeostasis. Because disruption of GLI transcriptional activity in taste papilla epithelium is sufficient to drive taste organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings suggest that taste

  14. Aberrant Hedgehog ligands induce progressive pancreatic fibrosis by paracrine activation of myofibroblasts and ductular cells in transgenic zebrafish.

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    In Hye Jung

    Full Text Available Hedgehog (Hh signaling is frequently up-regulated in fibrogenic pancreatic diseases including chronic pancreatitis and pancreatic cancer. Although recent series suggest exclusive paracrine activation of stromal cells by Hh ligands from epithelial components, debates still exist on how Hh signaling works in pathologic conditions. To explore how Hh signaling affects the pancreas, we investigated transgenic phenotypes in zebrafish that over-express either Indian Hh or Sonic Hh along with green fluorescence protein (GFP to enable real-time observation, or GFP alone as control, at the ptf1a domain. Transgenic embryos and zebrafish were serially followed for transgenic phenotypes, and investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR, in situ hybridization, and immunohistochemistry. Over-expression of Ihh or Shh reveals virtually identical phenotypes. Hh induces morphologic changes in a developing pancreas without derangement in acinar differentiation. In older zebrafish, Hh induces progressive pancreatic fibrosis intermingled with proliferating ductular structures, which is accompanied by the destruction of the acinar structures. Both myofibroblasts and ductular are activated and proliferated by paracrine Hh signaling, showing restricted expression of Hh downstream components including Patched1 (Ptc1, Smoothened (Smo, and Gli1/2 in those Hh-responsive cells. Hh ligands induce matrix metalloproteinases (MMPs, especially MMP9 in all Hh-responsive cells, and transform growth factor-ß1 (TGFß1 only in ductular cells. Aberrant Hh over-expression, however, does not induce pancreatic tumors. On treatment with inhibitors, embryonic phenotypes are reversed by either cyclopamine or Hedgehog Primary Inhibitor-4 (HPI-4. Pancreatic fibrosis is only prevented by HPI-4. Our study provides strong evidence of Hh signaling which induces pancreatic fibrosis through paracrine activation of Hh-responsive cells in vivo. Induction of

  15. Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells

    OpenAIRE

    Chen, Weiwei; Tang, Tracy; Eastham-Anderson, Jeff; Dunlap, Debra; Alicke, Bruno; Nannini, Michelle; Gould, Stephen; Yauch, Robert; Modrusan, Zora; DuPree, Kelly J.; Darbonne, Walter C.; Plowman, Greg; de Sauvage, Frederic J.; Callahan, Christopher A.

    2011-01-01

    Hedgehog (Hh) signaling is critical to the patterning and development of a variety of organ systems, and both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligands, activation occurs within the stromal microenvironment. Testing whether ligand-driven Hh signaling promotes tumor angiogenesis, we found that Hh antagonism reduced the vascular density of Hh-producing LS180 and SW480 xenograf...

  16. Blocking Hedgehog release from pancreatic cancer cells increases paracrine signaling potency

    NARCIS (Netherlands)

    Damhofer, Helene; Veenstra, Veronique L.; Tol, Johanna A. M. G.; van Laarhoven, Hanneke W. M.; Medema, Jan Paul; Bijlsma, Maarten F.

    2015-01-01

    Members of the Hedgehog (Hh) family of morphogens play crucial roles in development but are also involved in the progression of certain types of cancer. Despite being synthesized as hydrophobic dually lipid-modified molecules, and thus being strongly membrane-associated, Hh ligands are able to

  17. Loss of Sonic hedgehog leads to alterations in intestinal secretory cell maturation and autophagy.

    Directory of Open Access Journals (Sweden)

    Jessica Gagné-Sansfaçon

    Full Text Available BACKGROUND: Intestinal epithelial cells express the Sonic and Indian hedgehog ligands. Despite the strong interest in gut hedgehog signaling in GI diseases, no studies have specifically addressed the singular role of intestinal epithelial cell Sonic hedgehog signaling. The aim of this study was to investigate the specific role of Sonic hedgehog in adult ileal epithelial homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: A Sonic hedgehog intestinal epithelial conditional knockout mouse model was generated. Assessment of ileal histological abnormalities, crypt epithelial cell proliferation, epithelial cell fate, junctional proteins, signaling pathways, as well as ultrastructural analysis of intracellular organelles were performed in control and mutant mice. Mice lacking intestinal epithelial Sonic Hedgehog displayed decreased ileal crypt/villus length, decreased crypt proliferation as well as a decrease in the number of ileal mucin-secreting goblet cells and antimicrobial peptide-secreting Paneth cells during adult life. These secretory cells also exhibited disruption of their secretory products in mutant mice. Ultrastructural microscopy analysis revealed a dilated ER lumen in secretory cells. This phenotype was also associated with a decrease in autophagy. CONCLUSIONS/SIGNIFICANCE: Altogether, these findings indicate that the loss of Sonic hedgehog can lead to ileal secretory cell modifications indicative of endoplasmic reticulum stress, accompanied by a significant reduction in autophagy.

  18. The vitamin D receptor is required for activation of cWnt and hedgehog signaling in keratinocytes.

    Science.gov (United States)

    Lisse, Thomas S; Saini, Vaibhav; Zhao, Hengguang; Luderer, Hilary F; Gori, Francesca; Demay, Marie B

    2014-10-01

    Alopecia (hair loss) in vitamin D receptor (VDR)-null mice is due to absence of ligand-independent actions of the VDR that are required for initiation of postmorphogenic hair cycles. Investigations were undertaken to determine whether the VDR is required for the induction of signaling pathways that play an important role in this process. The induction of cWnt and hedgehog target genes that characterizes early anagen was found to be dramatically attenuated in VDR(-/-) mice, relative to wild-type (WT) mice. To determine whether this reflects impaired responsiveness to cWnt ligands, in vitro studies were performed in primary keratinocytes. These studies demonstrated impaired induction of cWnt target genes in response to Wnt3a in VDR(-/-) keratinocytes, relative to wild-type keratinocytes. Chromatin immunoprecipitation analyses revealed that the VDR was recruited to the regulatory regions of cWnt and hedgehog target genes in WT keratinocytes but not in VDR(-/-) or Lef1(-/-) keratinocytes. Lef1 was enriched on these same regulatory regions in WT keratinocytes but not in VDR(-/-) keratinocytes. In vivo studies were performed to determine whether activation of the hedgehog pathway could bypass the defect in cWnt signaling observed in the absence of the unliganded VDR. In WT, but not VDR(-/-), mice, hedgehog agonist treatment resulted in an induction of cWnt and hedgehog target genes and the generation of mature anagen hair follicles. Thus, these studies demonstrate that the unliganded VDR interacts with regulatory regions in the cWnt and hedgehog target genes and is required for the induction of these pathways during the postnatal hair cycle.

  19. Processing and turnover of the Hedgehog protein in the endoplasmic reticulum

    OpenAIRE

    Chen, Xin; Tukachinsky, Hanna; Huang, Chih-Hsiang; Jao, Cindy; Chu, Yue-Ru; Tang, Hsiang-Yun; Mueller, Britta; Schulman, Sol; Rapoport, Tom A.; Salic, Adrian

    2011-01-01

    The Hedgehog (Hh) signaling pathway has important functions during metazoan development. The Hh ligand is generated from a precursor by self-cleavage, which requires a free cysteine in the C-terminal part of the protein and results in the production of the cholesterol-modified ligand and a C-terminal fragment. In this paper, we demonstrate that these reactions occur in the endoplasmic reticulum (ER). The catalytic cysteine needs to form a disulfide bridge with a conserved cysteine, which is s...

  20. A tale of three hedgehogs

    OpenAIRE

    Torres, Igor Arrieta

    2017-01-01

    [EN] In this work we study three topologies defined over the same set: the hedgehog. As the name suggests, the hedgehog can be described as a set of spines identified at a single point. The first topology on the hedgehog will be a quotient topology, and the resulting space will said to be the quotient hedgehog. The main feature of the next topology, which we shall refer to as the compact hedgehog, will, of course, be compactness. The third and last topology will be generated by a metric, and ...

  1. Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells

    Science.gov (United States)

    Chen, Weiwei; Tang, Tracy; Eastham-Anderson, Jeff; Dunlap, Debra; Alicke, Bruno; Nannini, Michelle; Gould, Stephen; Yauch, Robert; Modrusan, Zora; DuPree, Kelly J.; Darbonne, Walter C.; Plowman, Greg; de Sauvage, Frederic J.; Callahan, Christopher A.

    2011-01-01

    Hedgehog (Hh) signaling is critical to the patterning and development of a variety of organ systems, and both ligand-dependent and ligand-independent Hh pathway activation are known to promote tumorigenesis. Recent studies have shown that in tumors promoted by Hh ligands, activation occurs within the stromal microenvironment. Testing whether ligand-driven Hh signaling promotes tumor angiogenesis, we found that Hh antagonism reduced the vascular density of Hh-producing LS180 and SW480 xenografts. In addition, ectopic expression of sonic hedgehog in low-Hh–expressing DLD-1 xenografts increased tumor vascular density, augmented angiogenesis, and was associated with canonical Hh signaling within perivascular tumor stromal cells. To better understand the molecular mechanisms underlying Hh-mediated tumor angiogenesis, we established an Hh-sensitive angiogenesis coculture assay and found that fibroblast cell lines derived from a variety of human tissues were Hh responsive and promoted angiogenesis in vitro through a secreted paracrine signal(s). Affymetrix array analyses of cultured fibroblasts identified VEGF-A, hepatocyte growth factor, and PDGF-C as candidate secreted proangiogenic factors induced by Hh stimulation. Expression studies of xenografts and angiogenesis assays using combinations of Hh and VEGF-A inhibitors showed that it is primarily Hh-induced VEGF-A that promotes angiogenesis in vitro and augments tumor-derived VEGF to promote angiogenesis in vivo. PMID:21597001

  2. Hedgehog pathway regulators influence cervical cancer cell proliferation, survival and migration

    Energy Technology Data Exchange (ETDEWEB)

    Samarzija, Ivana [Ecole Polytechnique Federale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne (Switzerland); Beard, Peter, E-mail: peter.beard@epfl.ch [Ecole Polytechnique Federale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne (Switzerland)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer Unknown cellular mutations complement papillomavirus-induced carcinogenesis. Black-Right-Pointing-Pointer Hedgehog pathway components are expressed by cervical cancer cells. Black-Right-Pointing-Pointer Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. Black-Right-Pointing-Pointer Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.

  3. Hedgehog pathway regulators influence cervical cancer cell proliferation, survival and migration

    International Nuclear Information System (INIS)

    Samarzija, Ivana; Beard, Peter

    2012-01-01

    Highlights: ► Unknown cellular mutations complement papillomavirus-induced carcinogenesis. ► Hedgehog pathway components are expressed by cervical cancer cells. ► Hedgehog pathway activators and inhibitors regulate cervical cancer cell biology. ► Cell immortalization by papillomavirus and activation of Hedgehog are independent. -- Abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.

  4. Outfoxing the Hedgehog

    Science.gov (United States)

    Barbieri, Richard

    2011-01-01

    Jim Collins's "Good to Great" has attained near-scriptural status in organizations, including nonprofits, which Collins says constitute a third of his readers. The pivot point in "Good to Great" is the Hedgehog Concept. The "Hedgehog Concept" (HC), this author claims, is dangerous for schools because it distorts the nature of education. As Collins…

  5. Hedgehog-mediated paracrine interaction between hepatic stellate cells and marrow-derived mesenchymal stem cells

    International Nuclear Information System (INIS)

    Lin Nan; Tang Zhaofeng; Deng Meihai; Zhong Yuesi; Lin Jizong; Yang Xuhui; Xiang Peng; Xu Ruiyun

    2008-01-01

    During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis

  6. Hedgehog pathway mediates early acceleration of liver regeneration induced by a novel two-staged hepatectomy in mice.

    Science.gov (United States)

    Langiewicz, Magda; Schlegel, Andrea; Saponara, Enrica; Linecker, Michael; Borger, Pieter; Graf, Rolf; Humar, Bostjan; Clavien, Pierre A

    2017-03-01

    ALPPS, a novel two-staged approach for the surgical removal of large/multiple liver tumors, combines portal vein ligation (PVL) with parenchymal transection. This causes acceleration of compensatory liver growth, enabling faster and more extensive tumor removal. We sought to identify the plasma factors thought to mediate the regenerative acceleration following ALPPS. We compared a mouse model of ALPPS against PVL and additional control surgeries (n=6 per group). RNA deep sequencing was performed to identify candidate molecules unique to ALPPS liver (n=3 per group). Recombinant protein and a neutralizing antibody combined with appropriate surgeries were used to explore candidate functions in ALPPS (n=6 per group). Indian hedgehog (IHH/Ihh) levels were assessed in human ALPPS patient plasma (n=6). ALPPS in mouse confirmed significant acceleration of liver regeneration relative to PVL (pIhh mRNA, coding for a secreted ligand inducing hedgehog signaling, was uniquely upregulated in ALPPS liver (pIhh plasma levels rose 4h after surgery (pIhh alone was sufficient to induce ALPPS-like acceleration of liver growth. Conversely, blocking Ihh markedly inhibited the accelerating effects of ALPPS. In the small cohort of ALPPS patients, IHH tended to be elevated early after surgery. Ihh and hedgehog pathway activation provide the first mechanistic insight into the acceleration of liver regeneration triggered by ALPPS surgery. The accelerating potency of recombinant Ihh, and its potential effect in human ALPPS may lead to a clinical role for this protein. ALPPS, a novel two-staged hepatectomy, accelerates liver regeneration, thereby helping to treat patients with otherwise unresectable liver tumors. The molecular mechanisms behind this accelerated regeneration are unknown. Here, we elucidate that Indian hedgehog, a secreted ligand important for fetal development, is a crucial mediator of the regenerative acceleration triggered by ALPPS surgery. Copyright © 2016. Published by

  7. The role of the Hedgehog signaling pathway in cancer: A comprehensive review

    Directory of Open Access Journals (Sweden)

    Ana Marija Skoda

    2018-02-01

    Full Text Available The Hedgehog (Hh signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh], Patched receptor (Ptch1, Ptch2, Smoothened receptor (Smo, Suppressor of fused homolog (Sufu, kinesin protein Kif7, protein kinase A (PKA, and cyclic adenosine monophosphate (cAMP. The activator form of Gli travels to the nucleus and stimulates the transcription of the target genes by binding to their promoters. The main target genes of the Hh signaling pathway are PTCH1, PTCH2, and GLI1. Deregulation of the Hh signaling pathway is associated with developmental anomalies and cancer, including Gorlin syndrome, and sporadic cancers, such as basal cell carcinoma, medulloblastoma, pancreatic, breast, colon, ovarian, and small-cell lung carcinomas. The aberrant activation of the Hh signaling pathway is caused by mutations in the related genes (ligand-independent signaling or by the excessive expression of the Hh signaling molecules (ligand-dependent signaling – autocrine or paracrine. Several Hh signaling pathway inhibitors, such as vismodegib and sonidegib, have been developed for cancer treatment. These drugs are regarded as promising cancer therapies, especially for patients with refractory/advanced cancers.

  8. Activation of the hedgehog pathway in advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    McCormick Frank

    2004-10-01

    Full Text Available Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP, are detected in over 70% of prostate tumors with Gleason scores 8–10, but in only 22% of tumors with Gleason scores 3–6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu protein, a negative regulator of the hedgehog pathway. We find that Su(Fu protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu. Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27. High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3. We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. Conclusion Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have

  9. Detection of a pneumonia virus of mice (PVM) in an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS).

    Science.gov (United States)

    Madarame, Hiroo; Ogihara, Kikumi; Kimura, Moe; Nagai, Makoto; Omatsu, Tsutomu; Ochiai, Hideharu; Mizutani, Tetsyuya

    2014-09-17

    A pneumonia virus of mice (PVM) from an African hedgehog (Atelerix arbiventris) with suspected wobbly hedgehog syndrome (WHS) was detected and genetically characterized. The affected hedgehog had a nonsuppurative encephalitis with vacuolization of the white matter, and the brain samples yielded RNA reads highly homogeneous to PVM strain 15 (96.5% of full genomic sequence homology by analysis of next generation sequencing). PVM antigen was also detected in the brain and the lungs immunohistochemically. A PVM was strongly suggested as a causative agent of encephalitis of a hedgehog with suspected WHS. This is a first report of PVM infection in hedgehogs. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Metal ion sequestration: An exciting dimension for molecularly ...

    African Journals Online (AJOL)

    The use of a tight binding macrocyclic ligand to complex a metal ion so that this serves as receptee on the Molecularly Imprinted Polymer (MIP) receptor as described here affords a sequestration route for a targeted metal ion, with potential for environmental remediation and restoration applications. Ethylene glycol ...

  11. Sarcoptes scabiei on hedgehogs in New Zealand.

    Science.gov (United States)

    Kriechbaum, Caroline; Pomroy, William; Gedye, Kristene

    2018-03-01

    European hedgehogs (Erinaceus europaeus) were introduced into New Zealand from Britain during the period from 1869 to the early 1900s. The only mite found on New Zealand hedgehogs in early studies was Caparinia tripilis, with Sarcoptes scabiei first being reported in 1996. The aim of this study was to investigate the prevalence of Sarcoptes infestation on hedgehogs in New Zealand, the number of mites found and the degree of mange observed. Dead hedgehogs were collected from veterinary clinics, rescue centres, members of the public and from road-kill. Twenty-one (55.3%) of the animals examined had visible skin lesions. Both Caparinia and Sarcoptes mites were identified on microscopic examination with Sarcoptes the most common, being found on over 70% of animals examined (n = 38). The numbers of mites recovered after brushing the head and body ranged from 1 to 5659 (median = 341 mites) with only six animals (22.2%) having fewer than 10 Sarcoptes mites found. Caparinia mites were seen on fewer animals and generally in very low numbers. These findings indicate a change in the mite populations on hedgehogs in New Zealand and that infected animals develop the debilitating hyperkeratotic form of sarcoptic mange without an accompanying hypersensitivity response limiting numbers of mites. Analysis of the cox 1 gene of Sarcoptes from two hedgehogs showed close alignment to sequences derived from a pig with one and from a dog with the second. More work needs to be undertaken to identify the source(s) of the Sarcoptes found on hedgehogs in New Zealand and whether other mammalian hosts may be infected from contact with hedgehogs.

  12. Human Plasma Very Low Density Lipoprotein Carries Indian Hedgehog

    NARCIS (Netherlands)

    Queiroz, Karla C. S.; Tio, Rene A.; Zeebregts, Clark J.; Bijlsma, Maarten F.; Zijlstra, Felix; Badlou, Bahram; de Vries, Marcel; Ferreira, Carmen V.; Spek, C. Arnold; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2010-01-01

    Hedgehog is one of the major morphogens and fulfils critical functions in both the development and maintenance of the vasculature. Hedgehog is highly hydrophobic and its diffusion toward target tissues remains only partly understood. In Drosophila, hedgehog transport via lipophorins is relevant for

  13. Human Plasma Very Low Density Lipoprotein Carries Indian Hedgehog

    NARCIS (Netherlands)

    Queiroz, Karla C. S.; Tio, Rene A.; Zeebregts, Clark J.; Bijlsma, Maarten F.; Zijlstra, Felix; Badlou, Bahram; de Vries, Marcel; Ferreira, Carmen V.; Spek, C. Arnold; Peppelenbosch, Maikel P.; Rezaee, Farhad

    Hedgehog is one of the major morphogens and fulfils critical functions in both the development and maintenance of the vasculature. Hedgehog is highly hydrophobic and its diffusion toward target tissues remains only partly understood. In Drosophila, hedgehog transport via lipophorins is relevant for

  14. Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Promote Tumor Growth Through Hedgehog Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jin Qi

    2017-08-01

    Full Text Available Background/Aims: Mesenchymal stem/stromal cells (MSCs are known to home to sites of tumor microenvironments where they participate in the formation of the tumor microenvironment and to interplay with tumor cells. However, the potential functional effects of MSCs on tumor cell growth are controversial. Here, we, from the view of bone marrow MSC-derived exosomes, study the molecular mechanism of MSCs on the growth of human osteosarcoma and human gastric cancer cells. Methods: MSCs derived from human bone marrow (hBMSCs were isolated and cultured in complete DMEM/F12 supplemented with 10% exosome-depleted fetal bovine serum and 1% penicillin-streptomycin, cell culture supernatants containing exosomes were harvested and exosome purification was performed by ultracentrifugation. Osteosarcoma (MG63 and gastric cancer (SGC7901 cells, respectively, were treated with hBMSC-derived exosomes in the presence or absence of a small molecule inhibitor of Hedgehog pathway. Cell viability was measured by transwell invasion assay, scratch migration assay and CCK-8 test. The expression of the signaling molecules Smoothened, Patched-1, Gli1 and the ligand Shh were tested by western blot and RT-PCR. Results: In this study, we found that hBMSC-derived exosomes promoted MG63 and SGC7901 cell growth through the activation of Hedgehog signaling pathway. Inhibition of Hedgehog signaling pathway significantly suppressed the process of hBMSC-derived exosomes on tumor growth. Conclusion: Our findings demonstrated the new roles of hedgehog signaling pathway in the hBMSCs-derived exosomes induced tumor progression.

  15. Intestinal Hedgehog signaling in tumors and inflammation

    NARCIS (Netherlands)

    Büller, N.V.J.A.

    2015-01-01

    In this thesis we investigated the role of Hedgehog signaling in tumors and inflammation. By using an inducible Indian Hedgehog (Ihh) knockout mouse we show that Ihh signals via the mesenchyme to the proliferating cells in the crypt to attenuate proliferation. Despite its anti-proliferative role in

  16. Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

    Science.gov (United States)

    Lin, Neng-Yu; Distler, Alfiya; Beyer, Christian; Philipi-Schöbinger, Ariella; Breda, Silvia; Dees, Clara; Stock, Michael; Tomcik, Michal; Niemeier, Andreas; Dell'Accio, Francesco; Gelse, Kolja; Mattson, Mark P; Schett, Georg; Distler, Jörg Hw

    2016-11-01

    Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Mechanism of inhibition of the tumor suppressor Patched by Sonic Hedgehog

    OpenAIRE

    Tukachinsky, Hanna; Petrov, Kostadin; Watanabe, Miyako; Salic, Adrian

    2016-01-01

    The Hedgehog-signaling pathway plays key roles in animal development and physiology. Insufficient Hedgehog signaling causes birth defects, whereas uncontrolled signaling is implicated in cancer. Signaling is triggered by the secreted protein, Sonic Hedgehog, which inhibits the membrane protein Patched1, leading to pathway activation. Despite its fundamental importance, we do not understand how Sonic Hedgehog inhibits Patched1. Here, we uncover a critical interaction between the fatty-acid?mod...

  18. Processing and turnover of the Hedgehog protein in the endoplasmic reticulum.

    Science.gov (United States)

    Chen, Xin; Tukachinsky, Hanna; Huang, Chih-Hsiang; Jao, Cindy; Chu, Yue-Ru; Tang, Hsiang-Yun; Mueller, Britta; Schulman, Sol; Rapoport, Tom A; Salic, Adrian

    2011-03-07

    The Hedgehog (Hh) signaling pathway has important functions during metazoan development. The Hh ligand is generated from a precursor by self-cleavage, which requires a free cysteine in the C-terminal part of the protein and results in the production of the cholesterol-modified ligand and a C-terminal fragment. In this paper, we demonstrate that these reactions occur in the endoplasmic reticulum (ER). The catalytic cysteine needs to form a disulfide bridge with a conserved cysteine, which is subsequently reduced by protein disulfide isomerase. Generation of the C-terminal fragment is followed by its ER-associated degradation (ERAD), providing the first example of an endogenous luminal ERAD substrate that is constitutively degraded. This process requires the ubiquitin ligase Hrd1, its partner Sel1, the cytosolic adenosine triphosphatase p97, and degradation by the proteasome. Processing-defective mutants of Hh are degraded by the same ERAD components. Thus, processing of the Hh precursor competes with its rapid degradation, explaining the impaired Hh signaling of processing-defective mutants, such as those causing human holoprosencephaly.

  19. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

    Directory of Open Access Journals (Sweden)

    Brigitte Teissedre

    Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

  20. Sonic hedgehog from both nerves and epithelium is a key trophic factor for taste bud maintenance.

    Science.gov (United States)

    Castillo-Azofeifa, David; Losacco, Justin T; Salcedo, Ernesto; Golden, Erin J; Finger, Thomas E; Barlow, Linda A

    2017-09-01

    The integrity of taste buds is intimately dependent on an intact gustatory innervation, yet the molecular nature of this dependency is unknown. Here, we show that differentiation of new taste bud cells, but not progenitor proliferation, is interrupted in mice treated with a hedgehog (Hh) pathway inhibitor (HPI), and that gustatory nerves are a source of sonic hedgehog (Shh) for taste bud renewal. Additionally, epithelial taste precursor cells express Shh transiently, and provide a local supply of Hh ligand that supports taste cell renewal. Taste buds are minimally affected when Shh is lost from either tissue source. However, when both the epithelial and neural supply of Shh are removed, taste buds largely disappear. We conclude Shh supplied by taste nerves and local taste epithelium act in concert to support continued taste bud differentiation. However, although neurally derived Shh is in part responsible for the dependence of taste cell renewal on gustatory innervation, neurotrophic support of taste buds likely involves a complex set of factors. © 2017. Published by The Company of Biologists Ltd.

  1. Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pengxiang; Nedelcu, Daniel; Watanabe, Miyako; Jao, Cindy; Kim, Youngchang; Liu, Jing; Salic, Adrian

    2016-08-01

    In vertebrates, sterols are necessary for Hedgehog signaling, a pathway critical in embryogenesis and cancer. Sterols activate the membrane protein Smoothened by binding its extracellular, cysteine-rich domain (CRD). Major unanswered questions concern the nature of the endogenous, activating sterol and the mechanism by which it regulates Smoothened. We report crystal structures of CRD complexed with sterols and alone, revealing that sterols induce a dramatic conformational change of the binding site, which is sufficient for Smoothened activation and is unique among CRD-containing receptors. We demonstrate that Hedgehog signaling requires sterol binding to Smoothened and define key residues for sterol recognition and activity. We also show that cholesterol itself binds and activates Smoothened. Furthermore, the effect of oxysterols is abolished in Smoothened mutants that retain activation by cholesterol and Hedgehog. We propose that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol.

  2. Megalin functions as an endocytic sonic hedgehog receptor.

    Science.gov (United States)

    McCarthy, Robert A; Barth, Jeremy L; Chintalapudi, Mastan R; Knaak, Christian; Argraves, W Scott

    2002-07-12

    Embryos deficient in the morphogen Sonic hedgehog (Shh) or the endocytic receptor megalin exhibit common neurodevelopmental abnormalities. Therefore, we have investigated the possibility that a functional relationship exists between the two proteins. During embryonic development, megalin was found to be expressed along the apical surfaces of neuroepithelial cells and was coexpressed with Shh in the ventral floor plate of the neural tube. Using enzyme-linked immunosorbent assay, homologous ligand displacement, and surface plasmon resonance techniques, it was found that the amino-terminal fragment of Shh (N-Shh) bound to megalin with high affinity. Megalin-expressing cells internalized N-Shh through a mechanism that was inhibited by antagonists of megalin, viz. anti-receptor-associated protein and anti-megalin antibodies. Heparin also inhibited N-Shh endocytosis, implicating proteoglycans in the internalization process, as has been described for other megalin ligands. Use of chloroquine to inhibit lysosomal proteinase activity showed that N-Shh endocytosed via megalin was not efficiently targeted to the lysosomes for degradation. The ability of megalin-internalized N-Shh to bypass lysosomes may relate to the finding that the interaction between N-Shh and megalin was resistant to dissociation with low pH. Together, these findings show that megalin is an efficient endocytic receptor for N-Shh. Furthermore, they implicate megalin as a new regulatory component of the Shh signaling pathway.

  3. Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.

    Science.gov (United States)

    Thorpe, Stephen D; Gambassi, Silvia; Thompson, Clare L; Chandrakumar, Charmilie; Santucci, Annalisa; Knight, Martin M

    2017-09-01

    Alkaptonuria (AKU) is a rare inherited disease resulting from a deficiency of the enzyme homogentisate 1,2-dioxygenase which leads to the accumulation of homogentisic acid (HGA). AKU is characterized by severe cartilage degeneration, similar to that observed in osteoarthritis. Previous studies suggest that AKU is associated with alterations in cytoskeletal organization which could modulate primary cilia structure/function. This study investigated whether AKU is associated with changes in chondrocyte primary cilia and associated Hedgehog signaling which mediates cartilage degradation in osteoarthritis. Human articular chondrocytes were obtained from healthy and AKU donors. Additionally, healthy chondrocytes were treated with HGA to replicate AKU pathology (+HGA). Diseased cells exhibited shorter cilia with length reductions of 36% and 16% in AKU and +HGA chondrocytes respectively, when compared to healthy controls. Both AKU and +HGA chondrocytes demonstrated disruption of the usual cilia length regulation by actin contractility. Furthermore, the proportion of cilia with axoneme breaks and bulbous tips was increased in AKU chondrocytes consistent with defective regulation of ciliary trafficking. Distribution of the Hedgehog-related protein Arl13b along the ciliary axoneme was altered such that its localization was increased at the distal tip in AKU and +HGA chondrocytes. These changes in cilia structure/trafficking in AKU and +HGA chondrocytes were associated with a complete inability to activate Hedgehog signaling in response to exogenous ligand. Thus, we suggest that altered responsiveness to Hedgehog, as a consequence of cilia dysfunction, may be a contributing factor in the development of arthropathy highlighting the cilium as a novel target in AKU. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

  4. WHEN AND WHY DO HEDGEHOGS AND FOXES DIFFER?

    Science.gov (United States)

    Keil, Frank C

    2010-01-01

    Philip E. Tetlock's finding that "hedgehog" experts (those with one big theory) are worse predictors than "foxes" (those with multiple, less comprehensive theories) offers fertile ground for future research. Are experts as likely to exhibit hedgehog- or fox-like tendencies in areas that call for explanatory, diagnostic, and skill-based expertise-as they did when Tetlock called on experts to make predictions? Do particular domains of expertise curtail or encourage different styles of expertise? Can we trace these different styles to childhood? Finally, can we nudge hedgehogs to be more like foxes? Current research can only grope at the answers to these questions, but they are essential to gauging the health of expert political judgment.

  5. Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

    OpenAIRE

    Caminero, A A; Machín, C; Sanchez-Toscano, F

    1992-01-01

    A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connecti...

  6. The radial-hedgehog solution in Landau–de Gennes' theory for nematic liquid crystals

    KAUST Repository

    MAJUMDAR, APALA

    2011-09-06

    We study the radial-hedgehog solution in a three-dimensional spherical droplet, with homeotropic boundary conditions, within the Landau-de Gennes theory for nematic liquid crystals. The radial-hedgehog solution is a candidate for a global Landau-de Gennes minimiser in this model framework and is also a prototype configuration for studying isolated point defects in condensed matter physics. The static properties of the radial-hedgehog solution are governed by a non-linear singular ordinary differential equation. We study the analogies between Ginzburg-Landau vortices and the radial-hedgehog solution and demonstrate a Ginzburg-Landau limit for the Landau-de Gennes theory. We prove that the radial-hedgehog solution is not the global Landau-de Gennes minimiser for droplets of finite radius and sufficiently low temperatures and prove the stability of the radial-hedgehog solution in other parameter regimes. These results contain quantitative information about the effect of geometry and temperature on the properties of the radial-hedgehog solution and the associated biaxial instabilities. © Copyright Cambridge University Press 2011.

  7. The radial-hedgehog solution in Landau–de Gennes' theory for nematic liquid crystals

    KAUST Repository

    MAJUMDAR, APALA

    2011-01-01

    We study the radial-hedgehog solution in a three-dimensional spherical droplet, with homeotropic boundary conditions, within the Landau-de Gennes theory for nematic liquid crystals. The radial-hedgehog solution is a candidate for a global Landau-de Gennes minimiser in this model framework and is also a prototype configuration for studying isolated point defects in condensed matter physics. The static properties of the radial-hedgehog solution are governed by a non-linear singular ordinary differential equation. We study the analogies between Ginzburg-Landau vortices and the radial-hedgehog solution and demonstrate a Ginzburg-Landau limit for the Landau-de Gennes theory. We prove that the radial-hedgehog solution is not the global Landau-de Gennes minimiser for droplets of finite radius and sufficiently low temperatures and prove the stability of the radial-hedgehog solution in other parameter regimes. These results contain quantitative information about the effect of geometry and temperature on the properties of the radial-hedgehog solution and the associated biaxial instabilities. © Copyright Cambridge University Press 2011.

  8. Generalidades de la señalización molecular durante el desarrollo embrionario: El caso del Sonic Hedgehog

    Directory of Open Access Journals (Sweden)

    David Arias

    2016-12-01

    Full Text Available Histogenesis and organogenesis of the vertebrates –including humans– involves the interaction of an epithelium (derived from the ectoderm and endoderm and the underlying mesenchyme (derived from the intraembryonic mesoderm. This interaction is regulated by a paracrine signaling network that includes several ligands and their respective receptors, in addition to a series of transcription factors that control the whole system. Among these factors are fibroblast growth factors (Fgf, Hedgehog family (Hh, Wingless family (Wnt and beta-fibroblast growth factor superfamily (Tgf-β, which act to organize the morphogenetic pattern of a tissue, an organ, an apparatus and a morphofunctional system. One of the most studied factors is Sonic hedgehog (Shh, which is essential for regulating the formation of morphogenetic fields in specific places of the embryo’s body schema through cell proliferation, differentiation, migration and cell survival processes –in development or in the adult–. Therefore, the purpose of this literature review is to describe the role of Shh in the embryonic development of the neural tube, the limbs and the teeth.

  9. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

    Science.gov (United States)

    Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

    2009-01-01

    Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

  10. The you gene encodes an EGF-CUB protein essential for Hedgehog signaling in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ian G Woods

    2005-03-01

    Full Text Available Hedgehog signaling is required for many aspects of development in vertebrates and invertebrates. Misregulation of the Hedgehog pathway causes developmental abnormalities and has been implicated in certain types of cancer. Large-scale genetic screens in zebrafish have identified a group of mutations, termed you-class mutations, that share common defects in somite shape and in most cases disrupt Hedgehog signaling. These mutant embryos exhibit U-shaped somites characteristic of defects in slow muscle development. In addition, Hedgehog pathway mutations disrupt spinal cord patterning. We report the positional cloning of you, one of the original you-class mutations, and show that it is required for Hedgehog signaling in the development of slow muscle and in the specification of ventral fates in the spinal cord. The you gene encodes a novel protein with conserved EGF and CUB domains and a secretory pathway signal sequence. Epistasis experiments support an extracellular role for You upstream of the Hedgehog response mechanism. Analysis of chimeras indicates that you mutant cells can appropriately respond to Hedgehog signaling in a wild-type environment. Additional chimera analysis indicates that wild-type you gene function is not required in axial Hedgehog-producing cells, suggesting that You is essential for transport or stability of Hedgehog signals in the extracellular environment. Our positional cloning and functional studies demonstrate that You is a novel extracellular component of the Hedgehog pathway in vertebrates.

  11. Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole.

    Science.gov (United States)

    Taniguchi, Yuka; Watanabe, Kenji; Mochii, Makoto

    2014-06-18

    Appendage regeneration in amphibians is regulated by the combinatorial actions of signaling molecules. The requirement of molecules secreted from specific tissues is reflected by the observation that the whole process of regeneration can be inhibited if a certain tissue is removed from the amputated stump. Interestingly, urodeles and anurans show different tissue dependencies during tail regeneration. The spinal cord is essential for tail regeneration in urodele but not in anuran larva, whereas the notochord but not the spinal cord is essential for tail regeneration in anuran tadpoles. Sonic hedgehog is one of the signaling molecules responsible for such phenomenon in axolotl, as hedgehog signaling is essential for overall tail regeneration and sonic hedgehog is exclusively expressed in the spinal cord. In order to know whether hedgehog signaling is involved in the molecular mechanism underlying the inconsistent tissue dependency for tail regeneration between anurans and urodeles, we investigated expression of hedgehog signal-related genes in the regenerating tail of Xenopus tadpole and examined the effect of the hedgehog signal inhibitor, cyclopamine, on the tail regeneration. In Xenopus, sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate. Overall regeneration was severely impaired in cyclopamine-treated tadpoles. Notochord maturation in the regenerate, including cell alignment and vacuolation, and myofiber formation were inhibited. Proliferation of spinal cord cells in the neural ampulla and of mesenchymal cells was also impaired. As in the axolotl, hedgehog signaling is required for multiple steps in tail regeneration in the Xenopus tadpole, although the location of the Shh source is quite different between the two species. This difference in Shh localization is the likely basis for the differing tissue requirement for tail regeneration between urodeles and anurans.

  12. Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-05-01

    Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

  13. Differential involvement of Hedgehog signaling in butterfly wing and eyespot development.

    Science.gov (United States)

    Tong, Xiaoling; Lindemann, Anna; Monteiro, Antónia

    2012-01-01

    Butterfly eyespots may have evolved from the recruitment of pre-existent gene circuits or regulatory networks into novel locations on the wing. Gene expression data suggests one such circuit, the Hedgehog (Hh) signaling pathway and its target gene engrailed (en), was recruited from a role in patterning the anterior-posterior insect wing axis to a role patterning butterfly eyespots. However, while Junonia coenia expresses hh and en both in the posterior compartment of the wing and in eyespot centers, Bicyclus anynana lacks hh eyespot-specific expression. This suggests that Hh signaling may not be functioning in eyespot development in either species or that it functions in J. coenia but not in B. anynana. In order to test these hypotheses, we performed functional tests of Hh signaling in these species. We investigated the effects of Hh protein sequestration during the larval stage on en expression levels, and on wing size and eyespot size in adults. Hh sequestration led to significantly reduced en expression and to significantly smaller wings and eyespots in both species. But while eyespot size in B. anynana was reduced proportionately to wing size, in J. coenia, eyespots were reduced disproportionately, indicating an independent role of Hh signaling in eyespot development in J. coenia. We conclude that while Hh signaling retains a conserved role in promoting wing growth across nymphalid butterflies, it plays an additional role in eyespot development in some, but not all, lineages of nymphalid butterflies. We discuss our findings in the context of alternative evolutionary scenarios that led to the differential expression of hh and other Hh pathway signaling members across nymphalid species.

  14. Differential involvement of Hedgehog signaling in butterfly wing and eyespot development.

    Directory of Open Access Journals (Sweden)

    Xiaoling Tong

    Full Text Available Butterfly eyespots may have evolved from the recruitment of pre-existent gene circuits or regulatory networks into novel locations on the wing. Gene expression data suggests one such circuit, the Hedgehog (Hh signaling pathway and its target gene engrailed (en, was recruited from a role in patterning the anterior-posterior insect wing axis to a role patterning butterfly eyespots. However, while Junonia coenia expresses hh and en both in the posterior compartment of the wing and in eyespot centers, Bicyclus anynana lacks hh eyespot-specific expression. This suggests that Hh signaling may not be functioning in eyespot development in either species or that it functions in J. coenia but not in B. anynana. In order to test these hypotheses, we performed functional tests of Hh signaling in these species. We investigated the effects of Hh protein sequestration during the larval stage on en expression levels, and on wing size and eyespot size in adults. Hh sequestration led to significantly reduced en expression and to significantly smaller wings and eyespots in both species. But while eyespot size in B. anynana was reduced proportionately to wing size, in J. coenia, eyespots were reduced disproportionately, indicating an independent role of Hh signaling in eyespot development in J. coenia. We conclude that while Hh signaling retains a conserved role in promoting wing growth across nymphalid butterflies, it plays an additional role in eyespot development in some, but not all, lineages of nymphalid butterflies. We discuss our findings in the context of alternative evolutionary scenarios that led to the differential expression of hh and other Hh pathway signaling members across nymphalid species.

  15. Sonic Hedgehog Signaling Regulates Hematopoietic Stem/Progenitor Cell Activation during the Granulopoietic Response to Systemic Bacterial Infection.

    Science.gov (United States)

    Shi, Xin; Wei, Shengcai; Simms, Kevin J; Cumpston, Devan N; Ewing, Thomas J; Zhang, Ping

    2018-01-01

    Activation and reprogramming of hematopoietic stem/progenitor cells play a critical role in the granulopoietic response to bacterial infection. Our current study determined the significance of Sonic hedgehog (SHH) signaling in the regulation of hematopoietic precursor cell activity during the host defense response to systemic bacterial infection. Bacteremia was induced in male Balb/c mice via intravenous injection (i.v.) of Escherichia coli (5 × 10 7 CFUs/mouse). Control mice received i.v. saline. SHH protein level in bone marrow cell (BMC) lysates was markedly increased at both 24 and 48 h of bacteremia. By contrast, the amount of soluble SHH ligand in marrow elutes was significantly reduced. These contrasting alterations suggested that SHH ligand release from BMCs was reduced and/or binding of soluble SHH ligand to BMCs was enhanced. At both 12 and 24 h of bacteremia, SHH mRNA expression by BMCs was significantly upregulated. This upregulation of SHH mRNA expression was followed by a marked increase in SHH protein expression in BMCs. Activation of the ERK1/2-SP1 pathway was involved in mediating the upregulation of SHH gene expression. The major cell type showing the enhancement of SHH expression in the bone marrow was lineage positive cells. Gli1 positioned downstream of the SHH receptor activation serves as a key component of the hedgehog (HH) pathway. Primitive hematopoietic precursor cells exhibited the highest level of baseline Gli1 expression, suggesting that they were active cells responding to SHH ligand stimulation. Along with the increased expression of SHH in the bone marrow, expression of Gli1 by marrow cells was significantly upregulated at both mRNA and protein levels following bacteremia. This enhancement of Gli1 expression was correlated with activation of hematopoietic stem/progenitor cell proliferation. Mice with Gli1 gene deletion showed attenuation in activation of marrow hematopoietic stem/progenitor cell proliferation and inhibition

  16. Loss of Pin1 Suppresses Hedgehog-Driven Medulloblastoma Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Tao Xu

    2017-03-01

    Full Text Available Medulloblastoma is the most common malignant brain tumor in children. Therapeutic approaches to medulloblastoma (combination of surgery, radiotherapy, and chemotherapy have led to significant improvements, but these are achieved at a high cost to quality of life. Alternative therapeutic approaches are needed. Genetic mutations leading to the activation of the Hedgehog pathway drive tumorigenesis in ~30% of medulloblastoma. In a yeast two-hybrid proteomic screen, we discovered a novel interaction between GLI1, a key transcription factor for the mediation of Hedgehog signals, and PIN1, a peptidylprolyl cis/trans isomerase that regulates the postphosphorylation fate of its targets. The GLI1/PIN1 interaction was validated by reciprocal pulldowns using epitope-tagged proteins in HEK293T cells as well as by co-immunoprecipiations of the endogenous proteins in a medulloblastoma cell line. Our results support a molecular model in which PIN1 promotes GLI1 protein abundance, thus contributing to the positive regulation of Hedgehog signals. Most importantly, in vivo functional analyses of Pin1 in the GFAP-tTA;TRE-SmoA1 mouse model of Hedgehog-driven medulloblastoma demonstrate that the loss of Pin1 impairs tumor development and dramatically increases survival. In summary, the discovery of the GLI1/PIN1 interaction uncovers PIN1 as a novel therapeutic target in Hedgehog-driven medulloblastoma tumorigenesis.

  17. The hedgehog system in ovarian follicles of cattle selected for twin ovulations and births: evidence of a link between the IGF and hedgehog systems

    Science.gov (United States)

    Hedgehog signaling is involved in regulation of ovarian function in Drosophila but its role in regulating mammalian ovarian folliculogenesis is less clear. Therefore, gene expression of Indian hedgehog (IHH) and its type 1 receptor, patched 1 (PTCH1), were quantified in bovine granulosa (GC) or the...

  18. TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy.

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F; Tang, Jen-Yang; Chang, Hsueh-Wei

    2017-07-14

    Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer.

  19. TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy

    Science.gov (United States)

    Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F.; Tang, Jen-Yang

    2017-01-01

    Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer. PMID:28708091

  20. Hedgehog signaling in development and homeostasis of the gastrointestinal tract

    NARCIS (Netherlands)

    van den Brink, Gijs R.

    2007-01-01

    The Hedgehog family of secreted morphogenetic proteins acts through a complex evolutionary conserved signaling pathway to regulate patterning events during development and in the adult organism. In this review I discuss the role of Hedgehog signaling in the development, postnatal maintenance, and

  1. Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniel L. Suzman

    2015-09-01

    Full Text Available Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.

  2. Discovery and characterization of a potent Wnt and hedgehog signaling pathways dual inhibitor.

    Science.gov (United States)

    Ma, Haikuo; Chen, Qin; Zhu, Fang; Zheng, Jiyue; Li, Jiajun; Zhang, Hongjian; Chen, Shuaishuai; Xing, Haimei; Luo, Lusong; Zheng, Long Tai; He, Sudan; Zhang, Xiaohu

    2018-04-10

    Embryonic stem cell pathways such as hedgehog and Wnt pathways are central to the tumorigenic properties of cancer stem cells (CSC). Since CSCs are characterized by their ability to self-renew, form differentiated progeny, and develop resistance to anticancer therapies, targeting the Wnt and hedgehog signaling pathways has been an important strategy for cancer treatment. Although molecules targeting either Wnt or hedgehog are common, to the best of our knowledge, those targeting both pathways have not been documented. Here we report a small molecule (compound 1) that inhibits both Wnt (IC 50  = 0.5 nM) and hedgehog (IC 50  = 71 nM) pathways based on reporter gene assays. We further identified that the molecular target of 1 for Wnt pathway inhibition was porcupine (a member of the membrane-bound O-acyltransferase family of proteins), a post-translational modification node in Wnt signaling; while the target of 1 mitigating hedgehog pathway was Smoothened, a key G protein coupled receptor (GPCR) mediating hedgehog signal transduction. Preliminary analysis of structure-activity-relationship identified key functional elements for hedgehog/Wnt inhibition. In in vivo studies, compound 1 demonstrated good oral exposure and bioavailability while eliciting no overt toxicity in mice. An important consideration in cancer treatment is the potential therapeutic escape through compensatory activation of an interconnected pathway when only one signaling pathway is inhibited. Toward this end, compound 1 may not only lead to the development of new therapeutics for Wnt and hedgehog related cancers, but may also help to develop potential cancer treatment which needs to target Wnt and hedgehog signaling simultaneously. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. The imidazopyridine derivative JK184 reveals dual roles for microtubules in Hedgehog signaling.

    Science.gov (United States)

    Cupido, Tommaso; Rack, Paul G; Firestone, Ari J; Hyman, Joel M; Han, Kyuho; Sinha, Surajit; Ocasio, Cory A; Chen, James K

    2009-01-01

    Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation (see figure).

  4. Static flexural properties of hedgehog spines conditioned in coupled temperature and relative humidity environments.

    Science.gov (United States)

    Kennedy, Emily B; Hsiung, Bor-Kai; Swift, Nathan B; Tan, Kwek-Tze

    2017-11-01

    Hedgehogs are agile climbers, scaling trees and plants to heights exceeding 10m while foraging insects. Hedgehog spines (a.k.a. quills) provide fall protection by absorbing shock and could offer insights for the design of lightweight, material-efficient, impact-resistant structures. There has been some study of flexural properties of hedgehog spines, but an understanding of how this keratinous biological material is affected by various temperature and relative humidity treatments, or how spine color (multicolored vs. white) affects mechanics, is lacking. To bridge this gap in the literature, we use three-point bending to analyze the effect of temperature, humidity, spine color, and their interactions on flexural strength and modulus of hedgehog spines. We also compare specific strength and stiffness of hedgehog spines to conventional engineered materials. We find hedgehog spine flexural properties can be finely tuned by modifying environmental conditioning parameters. White spines tend to be stronger and stiffer than multicolored spines. Finally, for most temperature and humidity conditioning parameters, hedgehog spines are ounce for ounce stronger than 201 stainless steel rods of the same diameter but as pliable as styrene rods with a slightly larger diameter. This unique combination of strength and elasticity makes hedgehog spines exemplary shock absorbers, and a suitable reference model for biomimicry. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Novel Hedgehog pathway targets against basal cell carcinoma

    International Nuclear Information System (INIS)

    Tang, Jean Y.; So, P.-L.; Epstein, Ervin H.

    2007-01-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence

  6. CO2 sequestration

    International Nuclear Information System (INIS)

    Favre, E.; Jammes, L.; Guyot, F.; Prinzhofer, A.; Le Thiez, P.

    2009-01-01

    This document presents the summary of a conference-debate held at the Academie des Sciences (Paris, France) on the topic of CO 2 sequestration. Five papers are reviewed: problems and solutions for the CO 2 sequestration; observation and surveillance of reservoirs; genesis of carbonates and geological storage of CO 2 ; CO 2 sequestration in volcanic and ultra-basic rocks; CO 2 sequestration, transport and geological storage: scientific and economical perspectives

  7. Radiological investigations of the hedgehog (Erinaceus concolor) appendicular skeleton.

    Science.gov (United States)

    Hashemi, Mohammad; Javadi, Shahram; Hadian, Mojtaba; Pourreza, Behzad; Behfar, Mahdi

    2009-03-01

    The normal radiographic anatomy of the healthy hedgehog can help to identify anatomic features unique to the hedgehog while comparing it with other small mammals, such as the dog and cat. Radiographic examination is a method that can play an important role in the diagnosis of a wide variety of skeletal diseases. Seven (2 males, 5 females) free-living hedgehogs (Erinaceus concolor) from the Urmia region of Iran were selected for this study. Lateral and craniocaudal radiographs from the front and hind limbs were obtained. The radiographs from these hedgehogs were compared with the normal canine and feline skeletal radiographic anatomy. On the forelimb radiographs, the clavicle was observed as a complete bone connected to the scapula and manubrium. There are three and five carpal bones in the proximal and distal rows, respectively, as in the dog and cat. The pelvis has a larger obturator foramen when compared with the dog and cat. In the lateral view, the pubis and ischium are relatively larger than in the dog and cat and have a more ventral position. The tarsal bones are similar to those of the dog and cat. The number of phalanges and sesamoid bones in the forelimb and hindlimb are likewise similar to those found in the dog and cat.

  8. Sonic Hedgehog Signaling Promotes Tumor Growth

    National Research Council Canada - National Science Library

    Bushman, Wade

    2007-01-01

    ... of the DOD New Investigator award indicate that Shh signaling promotes tumor growth. This proposal addresses the hypothesis that Sonic hedgehog signaling promotes tumor growth by activating stromal cell gene expression...

  9. Effects of a natural fire on a Kuenzler's hedgehog cactus (Echinocereus fendleri var. kuenzleri) and nylon hedgehog cactus (Echinocereus viridiflorus) population in Southeastern New Mexico

    Science.gov (United States)

    Robert C. Sivinski

    2007-01-01

    During the summer of 1992, a natural wildfire burned 250 acres of juniper savanna on Rawhide Ridge in the Guadalupe Mountains of southeastern New Mexico. This fire burned through the center of a Kuenzler's hedgehog cactus population. This threatened cactus is locally sympatric with the more abundant nylon hedgehog cactus, which has similar growth form and stature...

  10. Hedgehog pathway does not play a role in hidradenitis suppurativa pathogenesis

    DEFF Research Database (Denmark)

    Mozeika, E.; Jemec, G.B.E.; Nürnberg, B.M.

    2011-01-01

    in normal embryonic skin, hair follicle, sebaceous and sweat gland development. Mutations of hedgehog pathway in adult skin have previously been found in basal cell carcinomas and in alopecia as well as in epidermal cysts and in odontogenic keratocysts. Therefore, we suggested that the hedgehog pathway...

  11. Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development.

    Science.gov (United States)

    Nguyen, Duy; Fayol, Olivier; Buisine, Nicolas; Lecorre, Pierrette; Uguen, Patricia

    2016-01-01

    Studying the dynamic of gene regulatory networks is essential in order to understand the specific signals and factors that govern cell proliferation and differentiation during development. This also has direct implication in human health and cancer biology. The general transcriptional elongation regulator P-TEFb regulates the transcriptional status of many developmental genes. Its biological activity is controlled by an inhibitory complex composed of HEXIM and the 7SK snRNA. Here, we examine the function of HEXIM during Drosophila development. Our key finding is that HEXIM affects the Hedgehog signaling pathway. HEXIM knockdown flies display strong phenotypes and organ failures. In the wing imaginal disc, HEXIM knockdown initially induces ectopic expression of Hedgehog (Hh) and its transcriptional effector Cubitus interuptus (Ci). In turn, deregulated Hedgehog signaling provokes apoptosis, which is continuously compensated by apoptosis-induced cell proliferation. Thus, the HEXIM knockdown mutant phenotype does not result from the apoptotic ablation of imaginal disc; but rather from the failure of dividing cells to commit to a proper developmental program due to Hedgehog signaling defects. Furthermore, we show that ci is a genetic suppressor of hexim. Thus, HEXIM ensures the integrity of Hedgehog signaling in wing imaginal disc, by a yet unknown mechanism. To our knowledge, this is the first time that the physiological function of HEXIM has been addressed in such details in vivo.

  12. Functional Interaction between HEXIM and Hedgehog Signaling during Drosophila Wing Development.

    Directory of Open Access Journals (Sweden)

    Duy Nguyen

    Full Text Available Studying the dynamic of gene regulatory networks is essential in order to understand the specific signals and factors that govern cell proliferation and differentiation during development. This also has direct implication in human health and cancer biology. The general transcriptional elongation regulator P-TEFb regulates the transcriptional status of many developmental genes. Its biological activity is controlled by an inhibitory complex composed of HEXIM and the 7SK snRNA. Here, we examine the function of HEXIM during Drosophila development. Our key finding is that HEXIM affects the Hedgehog signaling pathway. HEXIM knockdown flies display strong phenotypes and organ failures. In the wing imaginal disc, HEXIM knockdown initially induces ectopic expression of Hedgehog (Hh and its transcriptional effector Cubitus interuptus (Ci. In turn, deregulated Hedgehog signaling provokes apoptosis, which is continuously compensated by apoptosis-induced cell proliferation. Thus, the HEXIM knockdown mutant phenotype does not result from the apoptotic ablation of imaginal disc; but rather from the failure of dividing cells to commit to a proper developmental program due to Hedgehog signaling defects. Furthermore, we show that ci is a genetic suppressor of hexim. Thus, HEXIM ensures the integrity of Hedgehog signaling in wing imaginal disc, by a yet unknown mechanism. To our knowledge, this is the first time that the physiological function of HEXIM has been addressed in such details in vivo.

  13. To Sequestrate or not to Sequestrate in View of the National Credit ...

    African Journals Online (AJOL)

    Keywords: Advantage of creditors; civil suit; compulsory sequestration; concursus creditorum; credit agreements; debt counsellor; debt enforcement; debt relief measures; debt restructuring; debt review; discretion of court; National Credit Act; NCA; reckless credit; Section 129 notice; sequestration; sequestration applications; ...

  14. [Hedgehog fungi in a dermatological office in Munich : Case reports and review].

    Science.gov (United States)

    Kargl, A; Kosse, B; Uhrlaß, S; Koch, D; Krüger, C; Eckert, K; Nenoff, P

    2018-02-12

    Patient 1: After contact to a central European hedgehog (Erinaceus europaeus), a 50-year-old female with atopy developed erythrosquamous tinea manus on the thumb and thenar eminence of the right hand. The patient had previously been scalded by hot steam at the affected site. The zoophilic dermatophyte Trichophyton erinacei could be cultured from the hedgehog as well as from scrapings from the woman's skin. Antifungal treatment of the hedgehog was initiated using 2 weekly cycles of itraconazole solution (0.1 ml/kg body weight, BW). In addition, every other day enilconazole solution was used for topical treatment. The patient was treated with ciclopirox olamine cream and oral terbinafine 250 mg daily for 2 weeks, which led to healing of the Tinea manus .Patient 2: An 18-year-old woman presented for emergency consultation with rimmed, papulous, vesicular and erosive crusted skin lesions of the index finger, and an erythematous dry scaling round lesion on the thigh. The patient worked at an animal care facility, specifically caring for hedgehogs. One of the hedgehogs suffered from a substantial loss of spines. Fungal cultures from skin scrapings of both lesions yielded T. erinacei. Treatment with ciclopirox olamine cream and oral terbinafine 250 mg for 14 days was initiated which led to healing of the lesions. Identification of all three T. erinacei isolates from both patients and from the hedgehog was confirmed by sequencing of the internal transcribed spacer (ITS) region of the ribosomal DNA, and of the translation elongation factor (TEF)-1-alpha gene. Using ITS sequencing discrimination between T. erinacei strains from European and from African hedgehogs is possible. T. erinacei should be considered a so-called emerging pathogen. In Germany the zoophilic dermatophyte T. erinacei should be taken into account as causative agent of dermatomycoses in humans after contact to hedgehogs.

  15. Ectopic Overexpression of Sonic Hedgehog (Shh Induces Stromal Expansion and Metaplasia in the Adult Murine Pancreas

    Directory of Open Access Journals (Sweden)

    Volker Fendrich

    2011-10-01

    Full Text Available Ligand-dependent activation of the Hedgehog (Hh signaling pathway has been implicated in both tumor initiation and metastasis of pancreatic ductal adenocarcinoma (PDAC. Prior studies in genetically engineered mouse models (GEMMs have assessed the role of Hh signaling by cell autonomous expression of a constitutively active Gli2 within epithelial cells. On the contrary, aberrant pathway reactivation in the human exocrine pancreas occurs principally as a consequence of Sonic Hh ligand (Shh overexpression from epithelial cells. To recapitulate the cognate pathophysiology of Hh signaling observed in the human pancreas, we examined GEMM where Hh ligand is conditionally overexpressed within the mature exocrine pancreas using a tamoxifen-inducible Elastase-Cre promoter (Ela-CreERT2;LSL-mShh. We also facilitated potential cell autonomous epithelial responsiveness to secreted Hh ligand by generating compound transgenic mice with concomitant expression of the Hh receptor Smoothened (Ela-CreERT2;LSL-mShh;LSL-mSmo. Of interest, none of these mice developed intraductal precursor lesions or PDAC during the follow-up period of up to 12 months after tamoxifen induction. Instead, all animals demonstrated marked expansion of stromal cells, consistent with the previously described epithelial-to-stromal paracrine Hh signaling. Hh responsiveness was mirrored by the expression of primary cilia within the expanded mesenchymal compartment and the absence within mature acinar cells. In the absence of cooperating mutations, Hh ligand overexpression in the mature exocrine pancreas is insufficient to induce neoplasia, even when epithelial cells coexpress the Smo receptor. This autochthonous model serves as a platform for studying epithelial stromal interactions in pancreatic carcinogenesis.

  16. Participation of Polycomb group gene extra sex combs in hedgehog signaling pathway

    International Nuclear Information System (INIS)

    Shindo, Norihisa; Sakai, Atsushi; Yamada, Kouji; Higashinakagawa, Toru

    2004-01-01

    Polycomb group (PcG) genes are required for stable inheritance of epigenetic states across cell divisions, a phenomenon termed cellular memory. PcG proteins form multimeric nuclear complex which modifies the chromatin structure of target site. Drosophila PcG gene extra sex combs (esc) and its vertebrate orthologs constitute a member of ESC-E(Z) complex, which possesses histone methyltransferase activity. Here we report isolation and characterization of medaka esc homolog, termed oleed. Hypomorphic knock-down of oleed using morpholino antisense oligonucleotides resulted in the fusion of eyes, termed cyclopia. Prechordal plate formation was not substantially impaired, but expression of hedgehog target genes was dependent on oleed, suggesting some link with hedgehog signaling. In support of this implication, histone methylation, which requires the activity of esc gene product, is increased in hedgehog stimulated mouse NIH-3T3 cells. Our data argue for the novel role of esc in hedgehog signaling and provide fundamental insight into the epigenetic mechanisms in general

  17. Arsenic inhibits hedgehog signaling during P19 cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jui Tung [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Bain, Lisa J., E-mail: lbain@clemson.edu [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States)

    2014-12-15

    Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and altered locomotor activity, while in vitro studies have shown that arsenite decreased muscle and neuronal cell differentiation. The sonic hedgehog (Shh) signaling pathway plays an important role during the differentiation of both neurons and skeletal muscle. The purpose of this study was to investigate whether arsenic can disrupt Shh signaling in P19 mouse embryonic stem cells, leading to changes muscle and neuronal cell differentiation. P19 embryonic stem cells were exposed to 0, 0.25, or 0.5 μM of sodium arsenite for up to 9 days during cell differentiation. We found that arsenite exposure significantly reduced transcript levels of genes in the Shh pathway in both a time and dose-dependent manner. This included the Shh ligand, which was decreased 2- to 3-fold, the Gli2 transcription factor, which was decreased 2- to 3-fold, and its downstream target gene Ascl1, which was decreased 5-fold. GLI2 protein levels and transcriptional activity were also reduced. However, arsenic did not alter GLI2 primary cilium accumulation or nuclear translocation. Moreover, additional extracellular SHH rescued the inhibitory effects of arsenic on cellular differentiation due to an increase in GLI binding activity. Taken together, we conclude that arsenic exposure affected Shh signaling, ultimately decreasing the expression of the Gli2 transcription factor. These results suggest a mechanism by which arsenic disrupts cell differentiation. - Highlights: • Arsenic exposure decreases sonic hedgehog pathway-related gene expression. • Arsenic decreases GLI2 protein levels and transcriptional activity in P19 cells. • Arsenic exposure does not alter the levels of SHH

  18. Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling

    Science.gov (United States)

    Luchetti, Giovanni; Sircar, Ria; Kong, Jennifer H; Nachtergaele, Sigrid; Sagner, Andreas; Byrne, Eamon FX; Covey, Douglas F; Siebold, Christian; Rohatgi, Rajat

    2016-01-01

    Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility. DOI: http://dx.doi.org/10.7554/eLife.20304.001 PMID:27705744

  19. OSTEOSARCOMA IN AFRICAN HEDGEHOGS (ATELERIX ALBIVENTRIS): FIVE CASES.

    Science.gov (United States)

    Reyes-Matute, Alonso; Méndez-Bernal, Adriana; Ramos-Garduño, Liliana-Aurora

    2017-06-01

    Osteosarcomas are unusual neoplasms in African hedgehogs ( Atelerix albiventris ) and have been reported in extraskeletal and skeletal locations, including mandible, ribs, and vertebra. Five hedgehogs with osteosarcoma submitted to the Pathology Department at Facultad de Medicina Veterinaria y Zootecnia, National Autonomous University of Mexico are reported. In two cases, the neoplasm arose from the skull; one case arose from the ribs with associated compression of the thoracic and abdominal cavity, and another case involved the vertebrae. In the last case, the neoplasm arose from the scapula. Histologic lesions were similar in all cases and consisted of well-demarcated nodules in which neoplastic cells were arranged in sheets of polyhedral to spindle-shaped cells with interspersed areas of necrosis. Numerous trabeculae of osteoid were present throughout the tumors. No metastases were detected. The predominant histologic pattern was osteoblastic, but a telangiectatic-like pattern was observed in the vertebral osteosarcoma. Electron microscopy was performed in two cases, and malignant osteoblasts had features consistent with descriptions in other species, including deposits of hydroxyapatite in osteoid. According to these cases and previously published data, axial osteosarcomas are more frequent in contrast to appendicular osteosarcomas in African hedgehogs, and metastases are rare.

  20. The Zn Finger protein Iguana impacts Hedgehog signaling by promoting ciliogenesis

    Science.gov (United States)

    Glazer, Andrew; Wilkinson, Alex; Backer, Chelsea B.; Lapan, Sylvain; Gutzman, Jennifer H.; Cheeseman, Iain M.; Reddien, Peter W.

    2009-01-01

    Hedgehog signaling is critical for metazoan development and requires cilia for pathway activity. The gene iguana was discovered in zebrafish as required for Hedgehog signaling, and encodes a novel Zn finger protein. Planarians are flatworms with robust regenerative capacities and that utilize epidermal cilia for locomotion. RNA interference of Smed-iguana in the planarian S. mediterranea caused cilia loss and failure to regenerate new cilia, but did not cause defects similar to those observed in hedgehog(RNAi) animals. Smed-iguana gene expression was also similar in pattern to the expression of multiple other ciliogenesis genes, but was not required for expression of these ciliogenesis genes. iguana-defective zebrafish had too few motile cilia in pronephric ducts and in Kupffer's vesicle. Kupffer's vesicle promotes left-right asymmetry and iguana mutant embryos had left-right asymmetry defects. Finally, human Iguana proteins (dZIP1 and dZIP1L) localize to the basal bodies of primary cilia and, together, are required for primary cilia formation. Our results indicate that a critical and broadly conserved function for Iguana is in ciliogenesis and that this function has come to be required for Hedgehog signaling in vertebrates. PMID:19852954

  1. Absolute requirement of cholesterol binding for Hedgehog gradient formation in Drosophila

    Directory of Open Access Journals (Sweden)

    Antoine Ducuing

    2013-05-01

    How morphogen gradients are shaped is a major question in developmental biology, but remains poorly understood. Hedgehog (Hh is a locally secreted ligand that reaches cells at a distance and acts as a morphogen to pattern the Drosophila wing and the vertebrate neural tube. The proper patterning of both structures relies on the precise control over the slope of Hh activity gradient. A number of hypotheses have been proposed to explain Hh movement and hence graded activity of Hh. A crux to all these models is that the covalent binding of cholesterol to Hh N-terminus is essential to achieve the correct slope of the activity gradient. Still, the behavior of cholesterol-free Hh (Hh-N remains controversial: cholesterol has been shown to either increase or restrict Hh range depending on the experimental setting. Here, in fly embryos and wing imaginal discs, we show that cholesterol-free Hh diffuses at a long-range. This unrestricted diffusion of cholesterol-free Hh leads to an absence of gradient while Hh signaling strength remains uncompromised. These data support a model where cholesterol addition restricts Hh diffusion and can transform a leveled signaling activity into a gradient. In addition, our data indicate that the receptor Patched is not able to sequester cholesterol-free Hh. We propose that a morphogen gradient does not necessarily stem from the active transfer of a poorly diffusing molecule, but can be achieved by the restriction of a highly diffusible ligand.

  2. Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, John [Univ. of California, Berkeley, CA (United States)

    2015-01-21

    The uranyl cation (UO₂²⁺) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 Å) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration. The goal of this research is thus to broaden the coordination chemistry of the uranyl ion by studying new ligand systems via synthetic, structural, thermodynamic and computational methods. It is anticipated that this fundamental science will find use beyond actinide separation technologies in areas such as nuclear waste remediation and nuclear materials. The focus of this study is to synthesize uranyl complexes incorporating amidinate and guanidinate ligands. Both synthetic and computational methods are used to investigate novel equatorial ligand coordination and how this affects the basicity of the oxo ligands. Such an understanding will later apply to designing ligands incorporating functionalities that can bind uranyl both equatorially and axially for highly selective sequestration. Efficient and durable chromatography supports for lanthanide separation will be generated by (1) identifying robust peptoid-based ligands capable of binding different lanthanides with variable affinities, and (2) developing practical synthetic methods for the attachment of these ligands to Dowex ion exchange resins.

  3. Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

    International Nuclear Information System (INIS)

    Arnold, John

    2015-01-01

    The uranyl cation (UO 2 2+ ) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 Å) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration. The goal of this research is thus to broaden the coordination chemistry of the uranyl ion by studying new ligand systems via synthetic, structural, thermodynamic and computational methods. It is anticipated that this fundamental science will find use beyond actinide separation technologies in areas such as nuclear waste remediation and nuclear materials. The focus of this study is to synthesize uranyl complexes incorporating amidinate and guanidinate ligands. Both synthetic and computational methods are used to investigate novel equatorial ligand coordination and how this affects the basicity of the oxo ligands. Such an understanding will later apply to designing ligands incorporating functionalities that can bind uranyl both equatorially and axially for highly selective sequestration. Efficient and durable chromatography supports for lanthanide separation will be generated by (1) identifying robust peptoid-based ligands capable of binding different lanthanides with variable affinities, and (2) developing practical synthetic methods for the attachment of these ligands to Dowex ion exchange resins.

  4. Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

    Science.gov (United States)

    Caminero, A A; Machín, C; Sanchez-Toscano, F

    1992-02-01

    A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences.

  5. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

    International Nuclear Information System (INIS)

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-01-01

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration

  6. The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

    DEFF Research Database (Denmark)

    Clement, Christian A; Kristensen, Stine G; Møllgård, Kjeld

    2009-01-01

    Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent...... P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine...... development. These data support the conclusion that cardiac primary cilia are crucial in early heart development, where they partly coordinate hedgehog signaling....

  7. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

    International Nuclear Information System (INIS)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-01-01

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17α-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERα-selective agonist), diarylpropionitrile (DPN, an ERβ-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERα-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERβ-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

  8. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

    Science.gov (United States)

    Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-12-15

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17alpha-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERalpha-selective agonist), diarylpropionitrile (DPN, an ERbeta-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERalpha-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERbeta-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

  9. The Pathology of Wobbly Hedgehog Syndrome.

    Science.gov (United States)

    Díaz-Delgado, Josué; Whitley, Derick B; Storts, Ralph W; Heatley, Jill J; Hoppes, Sharman; Porter, Brian F

    2018-01-01

    Wobbly hedgehog syndrome (WHS) is a leading cause of neurologic disease in African pygmy hedgehogs (APHs; Atelerix albiventris). This study describes the signalment, clinical signs, gross, microscopic, and ultrastructural lesions of WHS in a cohort of 12 pet APHs. Microscopically, lesions consisted of status spongiosus of the white matter, typically bilateral and symmetrical, with myelin degeneration and loss that was accompanied by neuronal/axonal degeneration plus reactive microgliosis and mild, focal astrocytosis and astrogliosis. Lesions were most severe in the cerebellum and medulla oblongata, as well as cervical and thoracic spinal cord. Less affected areas were the corona radiata, corpus callosum, corpus striatum, internal capsule, and the mesencephalon. Ultrastructurally, the lesions consisted of splitting of the myelin sheath at the intraperiod line with subsequent focal expansion, resulting in status spongiosus, disruption, dilatation, rhexis, and phagocytosis. Based on these results, WHS is best described as a "spongy myelinopathy" with widespread central nervous system involvement.

  10. Ticks and Fleas Infestation on East Hedgehogs (Erinaceus concolor in Van Province, Eastern Region of Turkey

    Directory of Open Access Journals (Sweden)

    Yaşar Goz

    2015-10-01

    Full Text Available Background: Ixodid ticks (Acari: İxodidae and fleas (Siphonaptera are the major vectors of pathogens threatening animals and human healths. The aim of our study was to detect the infestation rates of East Hedgehogs (Erinaceus concolor with ticks and fleas in Van Province, eastern region of Turkey.Methods: We examined fleas and ticks infestation patterns in 21 hedgehogs, collected from three suburbs with the greater of number gardens. In order to estimate flea and tick infestation of hedgehogs, we immobilized the ectoparasites by treatment the body with a insecticide trichlorphon (Neguvon®-Bayer.Results: On the hedgehogs, 60 ixodid ticks and 125 fleas were detected. All of the ixodid ticks were Rhipicephalus turanicus and all of the fleas were Archaeopsylla erinacei. Infestation rate for ticks and fleas was detected 66.66 % and 100 %, respectively.Conclusion: We detected ticks (R. turanicus and fleas (A. erinacei in hedgehogs at fairly high rates. Since many ticks and fleas species may harbor on hedgehogs and transmit some tick-borne and flea-borne patogens, this results are the important in terms of veterinary and public health. 

  11. The hedgehog-signaling pathway is repressed during the osteogenic differentiation of dental follicle cells

    DEFF Research Database (Denmark)

    Morsczeck, Christian; Reck, A; Beck, H C

    2017-01-01

    of repressors of the hedgehog-signaling pathway such as Patched 1 (PTCH1), Suppressor of Fused (SUFU), and Parathyroid Hormone-Related Peptide (PTHrP). Previous studies suggested that hedgehog proteins induce the osteogenic differentiation of mesenchymal stem cells via a paracrine pathway. Indian hedgehog (IHH......) induced the expression of the osteogenic transcription factor RUNX2. However, a supplementation of the BMP2-based osteogenic differentiation medium with IHH did not induce the expression of RUNX2. Moreover, IHH inhibited slightly the ALP activity and the mineralization of osteogenic-differentiated DFCs...

  12. First report of acariasis by Caparinia tripilis in African hedgehogs, (Atelerix albiventris), in Costa Rica

    OpenAIRE

    Moreira, Andrés; Troyo, Adriana; Calderón-Arguedas, Olger

    2013-01-01

    The African hedgehog is one of the newly imported exotic pets which have been observed with increasing regularity in veterinary clinics in Costa Rica. Despite their popularity, information about their diseases is scarce. Within skin diseases of hedgehogs, mange caused by Capariniaspp. is a common diagnosis in other countries. Two adult African hedgehogs, one male and one female, were brought to a private clinic in Heredia, Costa Rica, with chronic pruritic dermatitis, scabs, nearly complete l...

  13. First report of acariasis by Caparinia tripilis in African hedgehogs, (Atelerix albiventris), in Costa Rica

    OpenAIRE

    Moreira,Andrés; Troyo,Adriana; Calderón-Arguedas,Olger

    2013-01-01

    The African hedgehog is one of the newly imported exotic pets which have been observed with increasing regularity in veterinary clinics in Costa Rica. Despite their popularity, information about their diseases is scarce. Within skin diseases of hedgehogs, mange caused by Caparinia spp. is a common diagnosis in other countries. Two adult African hedgehogs, one male and one female, were brought to a private clinic in Heredia, Costa Rica, with chronic pruritic dermatitis, scabs, nearly complete ...

  14. In vivo imaging of Hedgehog pathway activation with a nuclear fluorescent reporter.

    Directory of Open Access Journals (Sweden)

    John K Mich

    Full Text Available The Hedgehog (Hh pathway is essential for embryonic development and tissue regeneration, and its dysregulation can lead to birth defects and tumorigenesis. Understanding how this signaling mechanism contributes to these processes would benefit from an ability to visualize Hedgehog pathway activity in live organisms, in real time, and with single-cell resolution. We report here the generation of transgenic zebrafish lines that express nuclear-localized mCherry fluorescent protein in a Gli transcription factor-dependent manner. As demonstrated by chemical and genetic perturbations, these lines faithfully report Hedgehog pathway state in individual cells and with high detection sensitivity. They will be valuable tools for studying dynamic Gli-dependent processes in vertebrates and for identifying new chemical and genetic regulators of the Hh pathway.

  15. Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

    Science.gov (United States)

    Caminero, A A; Machín, C; Sanchez-Toscano, F

    1992-01-01

    A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences. Images Fig. 2 Fig. 3 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1452481

  16. Ophthalmological abnormalities in wild European hedgehogs ...

    African Journals Online (AJOL)

    In this study we aimed to examine wild European hedgehogs (Erinaceus europaeus) in rescue centres and to determine ocular abnormalities in this animal population. Three hundred animals varying in age from 2 months to 5 years were examined, 147 being male and 153 female. All animals were evaluated with direct ...

  17. Smoothened-antagonists reverse homogentisic acid-induced alterations of Hedgehog signaling and primary cilium length in alkaptonuria.

    Science.gov (United States)

    Gambassi, Silvia; Geminiani, Michela; Thorpe, Stephen D; Bernardini, Giulia; Millucci, Lia; Braconi, Daniela; Orlandini, Maurizio; Thompson, Clare L; Petricci, Elena; Manetti, Fabrizio; Taddei, Maurizio; Knight, Martin M; Santucci, Annalisa

    2017-11-01

    Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated with HGA (66 µM) to replicate AKU cartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. © 2016 Wiley Periodicals, Inc.

  18. G-Protein Gαs controls medulloblastoma initiation by suppressing sonic hedgehog signaling.

    Science.gov (United States)

    He, Xuelian; Lu, Q Richard

    2015-01-01

    We identify Gαs as a novel tumor suppressor in medulloblastoma that functions principally by inhibition of sonic hedgehog signaling. Gαs not only stimulates cyclic adenosine monophosphate (cAMP)-dependent signaling but also inhibits ciliary trafficking of hedgehog components. Elevation of cAMP inhibits medulloblastoma growth and augments inhibition of smoothened to decrease tumor cell proliferation, thus highlighting Gαs as a potential therapeutic target.

  19. Hedgehog Signalling is Downregulated in Celiac Disease

    Directory of Open Access Journals (Sweden)

    Rui Liang

    2013-01-01

    Full Text Available BACKGROUND: Celiac disease (CD is a common autoimmune disorder of the small intestine that occurs in genetically predisposed individuals. Animal studies have suggested that the hedgehog (Hh signalling pathway is involved in gut inflammation, injury and repair.

  20. Integument Mycobiota of Wild European Hedgehogs (Erinaceus europaeus) from Catalonia, Spain.

    Science.gov (United States)

    Molina-López, R A; Adelantado, C; Arosemena, E L; Obón, E; Darwich, L; Calvo, M A

    2012-01-01

    There are some reports about the risk of manipulating wild hedgehogs since they can be reservoirs of potential zoonotic agents like dermatophytes. The aim of this study was to describe the integument mycobiota, with special attention to dermatophytes of wild European hedgehogs. Samples from spines and fur were cultured separately in Sabouraud dextrose agar (SDA) with antibiotic and dermatophyte test medium (DTM) plates. Nineteen different fungal genera were isolated from 91 cultures of 102 hedgehogs. The most prevalent genera were Cladosporium (79.1%), Penicillium (74.7%), Alternaria (64.8%), and Rhizopus (63.7%). A lower prevalence of Aspergillus (P = 0,035; χ (2) = 8,633) and Arthrinium (P = 0,043; χ (2) = 8,173) was isolated during the spring time and higher frequencies of Fusarium (P = 0,015; χ (2) = 10,533) during the autumn. The prevalence of Acremonium was significantly higher in young animals (70%, 26/37) than in adults (30%, 11/37) (P = 0,019; χ (2) = 5,915). Moreover, the majority of the saprophytic species that grew at the SDA culture were also detected at the DTM. Finally, no cases of ringworm were diagnosed and no dermatophytes spp. were isolated. Concluding, this study provides the first description of fungal mycobiota of the integument of wild European hedgehogs in Spain, showing a large number of saprophytic species and the absence of dermatophytes.

  1. Attenuation of hedgehog acyltransferase-catalyzed sonic Hedgehog palmitoylation causes reduced signaling, proliferation and invasiveness of human carcinoma cells

    DEFF Research Database (Denmark)

    Konitsiotis, Antonios D; Chang, Shu-Chun; Jovanović, Biljana

    2014-01-01

    ) cell line PANC-1 and transfected HEK293a cells Hhat localized to the endoplasmic reticulum. siRNA knockdown showed that Hhat is required for Sonic hedgehog (Shh) palmitoylation, for its assembly into high molecular weight extracellular complexes and for functional activity. Hhat knockdown inhibited Hh...

  2. Morphometrics of foramen magnum in African four-toed hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Girgiri, I; Olopade, J O; Yahaya, A

    The purpose of this study was to examine the morphometry of the foramen magnum of African four-toed hedgehog (Atelerix albiventris) in Maiduguri. Fourteen hedgehog skulls (7 male and 7 female each) were used for this study. The overall mean value of foramen magnum height and width were 0.51 ± 0.05 cm and 0.64 ± 0.04 cm while occipital condylar and interparacondylar widths were 1.00 ± 0.12 cm and 1.62 ± 0.07 cm, respectively. There was no significant difference between the two sexes. The foramen magnum index was 83.4 ± 5.51 cm in males and was significantly higher than 76.3 ± 6.37 cm observed in females. The presences of dorsal notches (occipital dysplasia) were observed, that were of three distinct types. It is envisaged, that the study will provide a valuable database on the anatomy of foramen magnum of hedgehogs in Nigeria for morphological, neurological, zooarchaeological, and comparative anatomical studies.

  3. Hedgehogs and Foxes at the Crossroads: Leadership and Diversity at the University of California

    Science.gov (United States)

    González, Cristina

    2011-01-01

    Following Clark Kerr's distinction between hedgehogs, or visionary leaders who know "one big thing," and foxes, or shrewd leaders who know "many things," this paper studies Kerr, an archetypical hedgehog, and David Gardner, a quintessential fox, as models for these two types of leaders. The paper also analyzes the hedgehog…

  4. Home Range Characteristics and Habitat Selection by Daurian Hedgehogs ( Mesechinus dauuricus in Ikh Nart Nature Reserve, Mongolia

    Directory of Open Access Journals (Sweden)

    Mirka Zapletal

    2012-12-01

    Full Text Available We examined home range characteristics and habitat selection of Daurian hedgehogs in Ikh Nart Nature Reserve, Mongolia. Home ranges of hedgehogs varied from 113.15 ha to 2,171.97 ha, and were larger in early summer than late summer. Hedgehogs showed relative preference for rocky outcrops and low-density shrub habitats, and relative avoidance of high- density shrub areas. Habitat selection also changed between early and late summer, shifting to greater use of low-density shrub areas and decreased use of forb-dominated short grass. Our baseline data on home ranges and habitat selection expand understanding of hedgehog ecology and provide guidance for future management decisions in Ikh Nart Nature Reserve and elsewhere in Mongolia.

  5. Hedgehog Signaling in Endochondral Ossification

    Directory of Open Access Journals (Sweden)

    Shinsuke Ohba

    2016-06-01

    Full Text Available Hedgehog (Hh signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects. Endochondral ossification is one of the notable developmental events in which Hh signaling acts as a master regulator. Among three Hh proteins in mammals, Indian hedgehog (Ihh is known to work as a major Hh input that induces biological impact of Hh signaling on the endochondral ossification. Ihh is expressed in prehypertrophic and hypertrophic chondrocytes of developing endochondral bones. Genetic studies so far have demonstrated that the Ihh-mediated activation of Hh signaling synchronizes chondrogenesis and osteogenesis during endochondral ossification by regulating the following processes: (1 chondrocyte differentiation; (2 chondrocyte proliferation; and (3 specification of bone-forming osteoblasts. Ihh not only forms a negative feedback loop with parathyroid hormone-related protein (PTHrP to maintain the growth plate length, but also directly promotes chondrocyte propagation. Ihh input is required for the specification of progenitors into osteoblast precursors. The combinatorial approaches of genome-wide analyses and mouse genetics will facilitate understanding of the regulatory mechanisms underlying the roles of Hh signaling in endochondral ossification, providing genome-level evidence of the potential of Hh signaling for the treatment of skeletal disorders.

  6. Hedgehog Signaling in Endochondral Ossification

    Science.gov (United States)

    Ohba, Shinsuke

    2016-01-01

    Hedgehog (Hh) signaling plays crucial roles in the patterning and morphogenesis of various organs within the bodies of vertebrates and insects. Endochondral ossification is one of the notable developmental events in which Hh signaling acts as a master regulator. Among three Hh proteins in mammals, Indian hedgehog (Ihh) is known to work as a major Hh input that induces biological impact of Hh signaling on the endochondral ossification. Ihh is expressed in prehypertrophic and hypertrophic chondrocytes of developing endochondral bones. Genetic studies so far have demonstrated that the Ihh-mediated activation of Hh signaling synchronizes chondrogenesis and osteogenesis during endochondral ossification by regulating the following processes: (1) chondrocyte differentiation; (2) chondrocyte proliferation; and (3) specification of bone-forming osteoblasts. Ihh not only forms a negative feedback loop with parathyroid hormone-related protein (PTHrP) to maintain the growth plate length, but also directly promotes chondrocyte propagation. Ihh input is required for the specification of progenitors into osteoblast precursors. The combinatorial approaches of genome-wide analyses and mouse genetics will facilitate understanding of the regulatory mechanisms underlying the roles of Hh signaling in endochondral ossification, providing genome-level evidence of the potential of Hh signaling for the treatment of skeletal disorders. PMID:29615586

  7. Gravitational black-holes-hedgehogs and two degenerate vacua of the Universe

    Science.gov (United States)

    Sidharth, B. G.; Das, C. R.; Laperashvili, L. V.; Nielsen, H. B.

    In the present paper, assuming the Multiple Point Principle (MPP) as a new law of Nature, we considered the existence of the two degenerate vacua of the Universe: the first Electroweak (EW) vacuum at v1 ≈ 246GeV — “true vacuum”, and the second Planck scale “false vacuum” at v2 ˜ 1018 GeV. In these vacua, we investigated different topological defects. The main aim of this paper is an investigation of the black-hole-hedgehogs configurations as defects of the false vacuum. In the framework of the f(R) gravity, described by the Gravi-Weak unification model, we considered a black-hole solution, which corresponds to a “hedgehog” — global monopole, that has been “swallowed” by the black-hole with mass core MBH ˜ 1018GeV and radius δ ˜ 10‑21GeV‑1. Considering the results of the hedgehog lattice theory in the framework of the SU(2) Yang-Mills gauge-invariant theory with hedgehogs in the Wilson loops, we have used the critical value of temperature for the hedgehogs confinement phase (Tc ˜ 1018GeV). This result gave us the possibility to conclude that the SM shows a new physics with contributions of the SU(2)-triplet Higgs bosons at the scale ˜10TeV. Theory predicts the stability of the EW-vacuum and the accuracy of the MPP.

  8. The generalized hedgehog and the projected chiral soliton model

    International Nuclear Information System (INIS)

    Fiolhais, M.; Kernforschungsanlage Juelich G.m.b.H.; Goeke, K.; Bochum Univ.; Gruemmer, F.; Urbano, J.N.

    1988-01-01

    The linear chiral soliton model with quark fields and elementary pion and sigma fields is solved in order to describe static properties of the nucleon and the delta resonance. To this end a Fock state of the system is constructed which consists of three valence quarks in a 1s orbit with a generalized hedgehog spin-flavour configuration cosηvertical strokeu↓> - sin ηvertical stroked↑>. Coherent states are used to provide a quantum description for the mesonic parts of the total wave function. The corresponding classical pion field also exhibits a generalized hedgehog structure. Various nucleon properties are calculated. These include proton and neutron charge raii, and the mangnetic moment of the proton for which experiment is obtained. (orig./HSI)

  9. Sox11 is required to maintain proper levels of Hedgehog signaling during vertebrate ocular morphogenesis.

    Directory of Open Access Journals (Sweden)

    Lakshmi Pillai-Kastoori

    2014-07-01

    Full Text Available Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders.

  10. The phylogenetic relationships of insectivores with special reference to the lesser hedgehog tenrec as inferred from the complete sequence of their mitochondrial genome.

    Science.gov (United States)

    Nikaido, Masato; Cao, Ying; Okada, Norihiro; Hasegawa, Masami

    2003-02-01

    The complete mitochondrial genome of a lesser hedgehog tenrec Echinops telfairi was determined in this study. It is an endemic African insectivore that is found specifically in Madagascar. The tenrec's back is covered with hedgehog-like spines. Unlike other spiny mammals, such as spiny mice, spiny rats, spiny dormice and porcupines, lesser hedgehog tenrecs look amazingly like true hedgehogs (Erinaceidae). However, they are distinguished morphologically from hedgehogs by the absence of a jugal bone. We determined the complete sequence of the mitochondrial genome of a lesser hedgehog tenrec and analyzed the results phylogenetically to determine the relationships between the tenrec and other insectivores (moles, shrews and hedgehogs), as well as the relationships between the tenrec and endemic African mammals, classified as Afrotheria, that have recently been shown by molecular analysis to be close relatives of the tenrec. Our data confirmed the afrotherian status of the tenrec, and no direct relation was recovered between the tenrec and the hedgehog. Comparing our data with those of others, we found that within-species variations in the mitochondrial DNA of lesser hedgehog tenrecs appear to be the largest recognized to date among mammals, apart from orangutans, which might be interesting from the view point of evolutionary history of tenrecs on Madagascar.

  11. Final Activity Report: The Effects of Iron Complexing Ligands on the Long Term Ecosystem Response to Iron Enrichment of HNLC waters

    Energy Technology Data Exchange (ETDEWEB)

    Trick, Charles Gordon [Western University

    2013-07-30

    Substantial increases in the concentrations of the stronger of two Fe(III) complexing organic ligand classes measured during the mesoscale Fe enrichment studies IronEx II and SOIREE appeared to sharply curtailed Fe availability to diatoms and thus limited the efficiency of carbon sequestration to the deep. Detailed observations during IronEx II (equatorial Pacific Ocean) and SOIREE (Southern Ocean –Pacific sector) indicate that the diatoms began re-experiencing Fe stress even though dissolved Fe concentrations remained elevated in the patch. This surprising outcome likely is related to the observed increased concentrations of strong Fe(III)-complexing ligands in seawater. Preliminary findings from other studies indicate that diatoms may not readily obtain Fe from these chemical species whereas Fe bound by strong ligands appears to support growth of cyanobacteria and nanoflagellates. The difficulty in assessing the likelihood of these changes with in-situ mesoscale experiments is the extended monitoring period needed to capture the long-term trajectory of the carbon cycle. A more detailed understanding of Fe complexing ligand effects on long-term ecosystem structure and carbon cycling is essential to ascertain not only the effect of Fe enrichment on short-term carbon sequestration in the oceans, but also the potential effect of Fe enrichment in modifying ecosystem structure and trajectory.

  12. Efficacy of a combination of 10% imidacloprid and 1% moxidectin against Caparinia tripilis in African pygmy hedgehog (Atelerix albiventris

    Directory of Open Access Journals (Sweden)

    Kim Kyu-Rim

    2012-08-01

    Full Text Available Abstract Background The efficacy and safety of a combination formulation of 10% imidacloprid + 1.0% moxidectin spot-on (Advocate® for Cats, Bayer Animal Health GmbH, Leverkusen, Germany was tested in 40 African pygmy hedgehogs (Atelerix albiventris naturally infested with Caparinia tripilis. Methods The optimal dosage level of the combination for hedgehogs was determined by assigning 20 hedgehogs into three treatment groups (0.1, 0.4 and 1.6 ml/Kg b.w., and one untreated control group of 5 hedgehogs each. Twenty naturally infested hedgehogs were then randomly assigned to either treatment or control group with 10 animals each, and the number of live mites was counted from 13 body regions on day 0, 3, 9, 16, and 30 after single treatment at the dosage level of 0.1 ml/Kg. Results Before the chemotherapy, the highest density of mite was observed in external ear canals followed by the dorsal and the lowest in the ventral regions of the body surface. The dosage level of 0.1 ml/Kg, which corresponded to the recommended dosage level for cats, containing 10 mg imidacloprid and 1 mg moxidectin was also the optimal dosage level for hedgehogs. No hedgehogs in the treatment group showed live mites from day 3 post treatment. Side effects such as ataxia, depression, nausea, and weight fluctuation were not observed during the whole period of study. Conclusions This report suggests that a combination formulation of 0.1 ml/Kg of 10% imidacloprid + 1% moxidectin spot-on for cats is also useful for the control of Caparinia tripilis infestation in hedgehogs.

  13. Hedgehogs (Erinaceus europaeus as a Source of Ectoparasites in Urban-suburban Areas of Northwest of Iran

    Directory of Open Access Journals (Sweden)

    Nasser Hajipour

    2015-10-01

    Full Text Available Background: Hedgehogs are small, nocturnal mammals which become popular in the world and have important role in transmission of zoonotic agents. Thus, the present study aimed to survey ectoparasite infestation from April 2010 to December 2011 in urban and suburban parts of Urmia and Tabriz Cities, Northwest of Iran.Methods: A total number of 84 hedgehogs (40 females and 44 males were examined. They have been carefully inspected for ectoparasites and collected arthropods were stored in 70% ethanol solution. The identification of arthropods was carried out using morphological diagnostic keys.Results: The occurrence of ticks on hedgehogs was 23 (67.7% with Rhipicephalus turanicus in Urmia and 11 (22% as well as 1(2% with Rh. turanicus and Hyalomma anatolicum anatolicum in Tabriz, respectively. One flea species, Archaeopsylla erinacei, was found with prevalence of 19 (55.9% and 27 (54% in Urmia and Tabriz Cities, respectively. Prevalence of infestation with Rh. turanicus and A. erinacei were not different (P> 0.05 between sexes of hedgehogs in two study areas. Highest prevalence of tick and flea infestation was in June in Urmia, whereas it was observed in August in Tabriz. Both tick and flea parasitizing hedgehogs showed seasonal difference in prevalence (P< 0.05 in Urmia, but it was not detected in Tabriz (P> 0.05.Conclusion: The result showed the high occurrence of ectoparasites in hedgehog population and according to the zoonotic potential of these animals as vector of some agents further studies are needed to investigate in different parts of Iran.

  14. The gross anatomy of the male reproductive system of the European hedgehog (Erinaceus Europaeus).

    Science.gov (United States)

    Akbari, G; Babaei, M; Kianifard, D; Mohebi, D

    2018-01-01

    Hedgehogs are small spiny-coated insectivores. Due to their low body weight, calm character, and easy maintenance, they are kept as pets. It is therefore worthwhile to care about hedgehogs' health problems and to provide pet owners with information about their reproduction. Moreover, it is necessary to be familiar with their anatomy so as to satisfy the need to improve nutrition and medical care, even surgery. This study was carried out on five adult male European hedgehogs euthanased in a chloroform chamber. The European hedgehog's oval testes are invisible in inguinal region because they have no true scrotal sac. The testes are located in the craniocaudal direction with dorsolateral epididymal attachments. The vesicular glands, the European hedgehog's largest accessory sex glands, are lobulated structures containing dorsomedial and ventrolateral parts on each side. The prostate is an oval gland with right and left lobes. The paired bulbourethral glands are laid on the ischiocavernosus muscle. Histologically the vesicular, prostate gland ducts and ductus deferens as well as urethra separately were discharged in a diverticlum at the level of the pelvic urethra end. A sigmoid flexure exists in the proximal part of shaft body of the penis. There are two retractor penile muscles. In dorsal end of the penile glans, there is a small urethral process with two nail- -like, needle-shaped structures. They are on both sides of the urethral process. Furthermore, there are two intromittent sacs (Sacculus urethralis) in the ventral part of the end of the penis. (Folia Morphol 2018; 77, 1: 36-43).

  15. Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea

    Science.gov (United States)

    Chen, Yan; Lu, Xiaoling; Guo, Luo; Ni, Wenli; Zhang, Yanping; Zhao, Liping; Wu, Lingjie; Sun, Shan; Zhang, Shasha; Tang, Mingliang; Li, Wenyan; Chai, Renjie; Li, Huawei

    2017-01-01

    Hair cell (HC) loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh) protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway. PMID:29311816

  16. Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2017-12-01

    Full Text Available Hair cell (HC loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway.

  17. Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

    Science.gov (United States)

    Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

    2017-12-01

    African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

  18. Topological spin-hedgehog crystals of a chiral magnet as engineered with magnetic anisotropy

    Science.gov (United States)

    Kanazawa, N.; White, J. S.; Rønnow, H. M.; Dewhurst, C. D.; Morikawa, D.; Shibata, K.; Arima, T.; Kagawa, F.; Tsukazaki, A.; Kozuka, Y.; Ichikawa, M.; Kawasaki, M.; Tokura, Y.

    2017-12-01

    We report the engineering of spin-hedgehog crystals in thin films of the chiral magnet MnGe by tailoring the magnetic anisotropy. As evidenced by neutron scattering on films with different thicknesses and by varying a magnetic field, we can realize continuously deformable spin-hedgehog crystals, each of which is described as a superposition state of a different set of three spin spirals (a triple-q state). The directions of the three propagation vectors q vary systematically, gathering from the three orthogonal 〈100 〉 directions towards the film normal as the strength of the uniaxial magnetic anisotropy and/or the magnetic field applied along the film normal increase. The formation of triple-q states coincides with the onset of topological Hall signals, that are ascribed to skew scattering by an emergent magnetic field originating in the nontrivial topology of spin hedgehogs. These findings highlight how nanoengineering of chiral magnets makes possible the rational design of unique topological spin textures.

  19. RANGELAND SEQUESTRATION POTENTIAL ASSESSMENT

    Energy Technology Data Exchange (ETDEWEB)

    Lee Spangler; George F. Vance; Gerald E. Schuman; Justin D. Derner

    2012-03-31

    Rangelands occupy approximately half of the world's land area and store greater than 10% of the terrestrial biomass carbon and up to 30% of the global soil organic carbon. Although soil carbon sequestration rates are generally low on rangelands in comparison to croplands, increases in terrestrial carbon in rangelands resulting from management can account for significant carbon sequestration given the magnitude of this land resource. Despite the significance rangelands can play in carbon sequestration, our understanding remains limited. Researchers conducted a literature review to identify sustainably management practices that conserve existing rangeland carbon pools, as well as increase or restore carbon sequestration potentials for this type of ecosystem. The research team also reviewed the impact of grazing management on rangeland carbon dynamics, which are not well understood due to heterogeneity in grassland types. The literature review on the impact of grazing showed a wide variation of results, ranging from positive to negative to no response. On further review, the intensity of grazing appears to be a major factor in controlling rangeland soil organic carbon dynamics. In 2003, researchers conducted field sampling to assess the effect of several drought years during the period 1993-2002. Results suggested that drought can significantly impact rangeland soil organic carbon (SOC) levels, and therefore, carbon sequestration. Resampling was conducted in 2006; results again suggested that climatic conditions may have overridden management effects on SOC due to the ecological lag of the severe drought of 2002. Analysis of grazing practices during this research effort suggested that there are beneficial effects of light grazing compared to heavy grazing and non-grazing with respect to increased SOC and nitrogen contents. In general, carbon storage in rangelands also increases with increased precipitation, although researchers identified threshold levels of

  20. Sex, age, and tissue specific accumulation of eight metals, arsenic, and selenium in the European hedgehog (Erinaceus europaeus).

    Science.gov (United States)

    Rautio, Anni; Kunnasranta, Mervi; Valtonen, Anu; Ikonen, Mirva; Hyvärinen, Heikki; Holopainen, Ismo J; Kukkonen, Jussi V K

    2010-11-01

    Many insectivores have been shown to be sensitive to heavy metals and therefore suitable for biomonitoring purposes. In Finland, the hibernation period of the European hedgehog (Erinaceus europaeus) is long, and during hibernation the stress caused by environmental toxins may be crucial. Concentrations of cadmium (Cd), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), arsenic (As), and selenium (Se) were measured in a population of hedgehogs in the town of Joensuu in eastern Finland during the summers of 2004 and 2005. The analyzed tissues were kidney, liver, hair, and spine. The sampled hedgehogs (n = 65) were mainly road-killed animals. As expected, the concentrations of heavy metals were low because the hedgehogs were living in a comparatively unpolluted area. Significant increases with age were found in Cd concentrations (kidney, liver, and spine) and some essential elements (Se in spine, kidney, and liver; Mo in kidney and liver; Cu in spine; Fe in liver; and Mn in spine). Age accumulation and correlations between Se and Cd and between Mo and Cd may indicate the protective roles of Se and Mo against Cd toxicity in hedgehogs, in which Cd is already at comparatively low concentrations. Sex had no significant effect on concentrations of the elements studied. In conclusion, age is an important parameter to be taken into account when studying heavy-metal concentrations in hedgehogs and other insectivores.

  1. Cryptosporidium erinacei n. sp. (Apicomplexa: Cryptosporidiidae) in hedgehogs

    Czech Academy of Sciences Publication Activity Database

    Kváč, Martin; Hofmannová, L.; Hlásková, Lenka; Květoňová, Dana; Vitovec, J.; McEvoy, J.; Sak, Bohumil

    2014-01-01

    Roč. 201, 1-2 (2014), s. 9-17 ISSN 0304-4017 R&D Projects: GA MŠk(CZ) LH11061 Institutional support: RVO:60077344 Keywords : Cryptosporidium erinacei * taxonomy * morphology * molecular analyses * transmission studies * Cryptosporidium hedgehog genotype Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.460, year: 2014

  2. Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey.

    Science.gov (United States)

    Schüz, A; Demianenko, G P

    1995-01-01

    Synapses and dendritic spines were investigated in the parietal cortex of the hedgehog (Erinaceus europaeus) and the monkey (Macaca mulatta). There was no significant difference in the density of synapses between the two species (14 synapses/100 microns2 in the hedgehog, 15/100 microns2 in the monkey), neither in the size of the synaptic junctions, in the proportion of Type I and Type II synapses (8-10% were of Type II in the hedgehog, 10-14% in the monkey) nor in the proportion of perforated synapses (8% in the hedgehog, 5% in the monkey). The only striking difference at the electron microscopic level concerned the frequency of synapses in which the postsynaptic profile was deeply indented into the presynaptic terminal. Such synapses were 10 times more frequent in the monkey. Dendritic spines were investigated in Golgi-preparations. The density of spines along dendrites was similar in both species. The results are discussed with regard to connectivity in the cortex of small and large brains.

  3. Making carbon sequestration a paying proposition

    Science.gov (United States)

    Han, Fengxiang X.; Lindner, Jeff S.; Wang, Chuji

    2007-03-01

    Atmospheric carbon dioxide (CO2) has increased from a preindustrial concentration of about 280 ppm to about 367 ppm at present. The increase has closely followed the increase in CO2 emissions from the use of fossil fuels. Global warming caused by increasing amounts of greenhouse gases in the atmosphere is the major environmental challenge for the 21st century. Reducing worldwide emissions of CO2 requires multiple mitigation pathways, including reductions in energy consumption, more efficient use of available energy, the application of renewable energy sources, and sequestration. Sequestration is a major tool for managing carbon emissions. In a majority of cases CO2 is viewed as waste to be disposed; however, with advanced technology, carbon sequestration can become a value-added proposition. There are a number of potential opportunities that render sequestration economically viable. In this study, we review these most economically promising opportunities and pathways of carbon sequestration, including reforestation, best agricultural production, housing and furniture, enhanced oil recovery, coalbed methane (CBM), and CO2 hydrates. Many of these terrestrial and geological sequestration opportunities are expected to provide a direct economic benefit over that obtained by merely reducing the atmospheric CO2 loading. Sequestration opportunities in 11 states of the Southeast and South Central United States are discussed. Among the most promising methods for the region include reforestation and CBM. The annual forest carbon sink in this region is estimated to be 76 Tg C/year, which would amount to an expenditure of 11.1-13.9 billion/year. Best management practices could enhance carbon sequestration by 53.9 Tg C/year, accounting for 9.3% of current total annual regional greenhouse gas emission in the next 20 years. Annual carbon storage in housing, furniture, and other wood products in 1998 was estimated to be 13.9 Tg C in the region. Other sequestration options

  4. First report of acariasis by Caparinia tripilis in African hedgehogs, (Atelerix albiventris), in Costa Rica.

    Science.gov (United States)

    Moreira, Andrés; Troyo, Adriana; Calderón-Arguedas, Olger

    2013-01-01

    The African hedgehog is one of the newly imported exotic pets which have been observed with increasing regularity in veterinary clinics in Costa Rica. Despite their popularity, information about their diseases is scarce. Within skin diseases of hedgehogs, mange caused by Caparinia spp. is a common diagnosis in other countries. Two adult African hedgehogs, one male and one female, were brought to a private clinic in Heredia, Costa Rica, with chronic pruritic dermatitis, scabs, nearly complete loss of spines, lethargy, dehydration, and weight loss. During physical exam, deposits of dry seborrhea were taken and processed for diagnosis. Microscopic examination revealed psoroptid mites identified as Caparinia tripilis. This is the first report of the presence of Caparinia tripilis in Costa Rica and, to the authors' knowledge, the rest of Central America.

  5. Hedgehog signaling in tumor cells facilitates osteoblast-enhanced osteolytic metastases.

    Directory of Open Access Journals (Sweden)

    Shamik Das

    Full Text Available The remodeling process in bone yields numerous cytokines and chemokines that mediate crosstalk between osteoblasts and osteoclasts and also serve to attract and support metastatic tumor cells. The metastatic tumor cells disturb the equilibrium in bone that manifests as skeletal complications. The Hedgehog (Hh pathway plays an important role in skeletogenesis. We hypothesized that the Hh pathway mediates an interaction between tumor cells and osteoblasts and influences osteoblast differentiation in response to tumor cells. We have determined that breast tumor cells have an activated Hh pathway characterized by upregulation of the ligand, IHH and transcription factor GLI1. Breast cancer cells interact with osteoblasts and cause an enhanced differentiation of pre-osteoblasts to osteoblasts that express increased levels of the osteoclastogenesis factors, RANKL and PTHrP. There is sustained expression of osteoclast-promoting factors, RANKL and PTHrP, even after the osteoblast differentiation ceases and apoptosis sets in. Moreover, tumor cells that are deficient in Hh signaling are compromised in their ability to induce osteoblast differentiation and consequently are inefficient in causing osteolysis. The stimulation of osteoblast differentiation sets the stage for osteoclast differentiation and overall promotes osteolysis. Thus, in the process of developing newer therapeutic strategies against breast cancer metastasis to bone it would worthwhile to keep in mind the role of the Hh pathway in osteoblast differentiation in an otherwise predominant osteolytic phenomenon.

  6. Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.

    Science.gov (United States)

    Renault, Marie-Ange; Chapouly, Candice; Yao, Qinyu; Larrieu-Lahargue, Frédéric; Vandierdonck, Soizic; Reynaud, Annabel; Petit, Myriam; Jaspard-Vinassa, Béatrice; Belloc, Isabelle; Traiffort, Elisabeth; Ruat, Martial; Duplàa, Cécile; Couffinhal, Thierry; Desgranges, Claude; Gadeau, Alain-Pierre

    2013-03-01

    Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle. This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.

  7. Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation

    International Nuclear Information System (INIS)

    Cherry, Amy L.; Finta, Csaba; Karlström, Mikael; Jin, Qianren; Schwend, Thomas; Astorga-Wells, Juan; Zubarev, Roman A.; Del Campo, Mark; Criswell, Angela R.; Sanctis, Daniele de; Jovine, Luca; Toftgård, Rune

    2013-01-01

    Crystal and small-angle X-ray scattering structures of full-length human SUFU alone and in complex with the conserved SYGHL motif from GLI transcription factors show major conformational changes associated with binding and reveal an intrinsically disordered region crucial for pathway activation. Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics

  8. Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation

    Energy Technology Data Exchange (ETDEWEB)

    Cherry, Amy L.; Finta, Csaba; Karlström, Mikael; Jin, Qianren; Schwend, Thomas [Karolinska Institutet, Novum, Hälsovägen 7, SE-141 83 Huddinge (Sweden); Astorga-Wells, Juan [Karolinska Institutet, Scheeles väg 2, SE-171 77 Stockholm (Sweden); Biomotif AB, Enhagsvägen 7, SE-182 12 Danderyd (Sweden); Zubarev, Roman A. [Karolinska Institutet, Scheeles väg 2, SE-171 77 Stockholm (Sweden); Del Campo, Mark; Criswell, Angela R. [Rigaku Americas Corporation, 9009 New Trails Drive, The Woodlands, TX 77381 (United States); Sanctis, Daniele de [European Synchrotron Radiation Facility, 6 Rue Jules Horowitz, 38043 Grenoble (France); Jovine, Luca, E-mail: luca.jovine@ki.se; Toftgård, Rune, E-mail: luca.jovine@ki.se [Karolinska Institutet, Novum, Hälsovägen 7, SE-141 83 Huddinge (Sweden)

    2013-12-01

    Crystal and small-angle X-ray scattering structures of full-length human SUFU alone and in complex with the conserved SYGHL motif from GLI transcription factors show major conformational changes associated with binding and reveal an intrinsically disordered region crucial for pathway activation. Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.

  9. Carbon sequestration.

    Science.gov (United States)

    Lal, Rattan

    2008-02-27

    Developing technologies to reduce the rate of increase of atmospheric concentration of carbon dioxide (CO2) from annual emissions of 8.6PgCyr-1 from energy, process industry, land-use conversion and soil cultivation is an important issue of the twenty-first century. Of the three options of reducing the global energy use, developing low or no-carbon fuel and sequestering emissions, this manuscript describes processes for carbon (CO2) sequestration and discusses abiotic and biotic technologies. Carbon sequestration implies transfer of atmospheric CO2 into other long-lived global pools including oceanic, pedologic, biotic and geological strata to reduce the net rate of increase in atmospheric CO2. Engineering techniques of CO2 injection in deep ocean, geological strata, old coal mines and oil wells, and saline aquifers along with mineral carbonation of CO2 constitute abiotic techniques. These techniques have a large potential of thousands of Pg, are expensive, have leakage risks and may be available for routine use by 2025 and beyond. In comparison, biotic techniques are natural and cost-effective processes, have numerous ancillary benefits, are immediately applicable but have finite sink capacity. Biotic and abiotic C sequestration options have specific nitches, are complementary, and have potential to mitigate the climate change risks.

  10. The role of nutraceuticals in the regulation of Wnt and Hedgehog signaling in cancer

    Science.gov (United States)

    Li, Yiwei; Wang, Zhiwei; Kong, Dejuan

    2010-01-01

    Multiple cellular signaling pathways have been involved in the processes of cancer cell invasion and metastasis. Among many signaling pathways, Wnt and Hedgehog (Hh) signaling pathways are critically involved in embryonic development, in the biology of cancer stem cells (CSCs) and in the acquisition of epithelial to mesenchymal transition (EMT), and thus this article will remain focused on Wnt and Hh signaling. Since CSCs and EMT are also known to be responsible for cancer cell invasion and metastasis, the Wnt and Hedgehog signaling pathways are also intimately associated with cancer invasion and metastasis. Emerging evidence suggests the beneficial role of chemopreventive agents commonly known as nutraceutical in cancer. Among many such agents, soy isoflavones, curcumin, green tea polyphenols, 3,3′-diindolylmethane, resveratrol, lycopene, vitamin D, etc. have been found to prevent, reverse, or delay the carcinogenic process. Interestingly, these agents have also shown to prevent or delay the progression of cancer, which could in part be due to their ability to attack CSCs or EMT-type cells by attenuating the Wnt and Hedgehog signaling pathways. In this review, we summarize the current state of our knowledge on the role of Wnt and Hedgehog signaling pathways, and their targeted inactivation by chemopreventive agents (nutraceuticals) for the prevention of tumor progression and/or treatment of human malignancies. PMID:20711635

  11. Zebrafish genetics gets the Scube on Hedgehog secretion.

    Science.gov (United States)

    Ingham, Philip W

    2012-11-15

    Inspired by a zebrafish mutation, two recent studies by Creanga and colleagues (pp. 1312-1325) and Tukachinsky and colleagues have shed new light on the way in which lipidated Hedgehog proteins are secreted and released from expressing cells, suggesting a model for the sequential action of the Disp and Scube2 proteins in this process.

  12. Dynamic impact testing of hedgehog spines using a dual-arm crash pendulum.

    Science.gov (United States)

    Swift, Nathan B; Hsiung, Bor-Kai; Kennedy, Emily B; Tan, Kwek-Tze

    2016-08-01

    Hedgehog spines are a potential model for impact resistant structures and material. While previous studies have examined static mechanical properties of individual spines, actual collision tests on spines analogous to those observed in the wild have not previously been investigated. In this study, samples of roughly 130 keratin spines were mounted vertically in thin substrates to mimic the natural spine layout on hedgehogs. A weighted crash pendulum was employed to induce and measure the effects of repeated collisions against samples, with the aim to evaluate the influence of various parameters including humidity effect, impact energy, and substrate hardness. Results reveal that softer samples-due to humidity conditioning and/or substrate material used-exhibit greater durability over multiple impacts, while the more rigid samples exhibit greater energy absorption performance at the expense of durability. This trend is exaggerated during high-energy collisions. Comparison of the results to baseline tests with industry standard impact absorbing foam, wherein the spines exhibit similar energy absorption, verifies the dynamic impact absorption capabilities of hedgehog spines and their candidacy as a structural model for engineered impact technology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. CO{sub 2} sequestration; Sequestration du CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Acket, C

    2008-04-15

    The carbon dioxide is the main gas associated to the human activity, generating consequences on the greenhouse effect. By the use of fossil fuels, the human activity generates each year, about 26 milliards of tons. Only the half of theses releases is absorbed by the nature, the rest reinforces the greenhouse effect. To reduce the emissions two actions are proposed: a better energy consumption and the development of technologies which do not produce, or weakly, greenhouse effect gases. Another way is studied: the carbon sequestration and geological storage. This document details the different technologies of sequestration, the transport and the underground storage. It discusses also the economical and legislative aspects, providing examples and projects. (A.L.B.)

  14. Comparison of two systemic antifungal agents, itraconazole and terbinafine, for the treatment of dermatophytosis in European hedgehogs (Erinaceus europaeus).

    Science.gov (United States)

    Bexton, Steve; Nelson, Helen

    2016-12-01

    Dermatophytosis caused by Trichophyton erinacei is a common scaling and crusting skin disease affecting European hedgehogs (Erinaceus europaeus) admitted to wildlife rescue centres. The application of topical therapy can be challenging because wild hedgehogs are subject to stress and often roll into a ball when handled. Systemic antifungal therapy is more convenient but has not been evaluated in this species. To compare the efficacy of oral itraconazole versus oral terbinafine for the treatment of dermatophytosis affecting hedgehogs. A treatment trial was undertaken in a wildlife hospital involving 165 hedgehogs with naturally occurring dermatophytosis. Animals were randomly divided into two groups and treated with either itraconazole or terbinafine orally for 28 days. The therapeutic efficacy was evaluated after 14 and 28 days by mycological culture and clinical dermatological lesion scores. Both drugs were well tolerated and clinically effective. After 14 and 28 days of treatment, the respective mycological cure rate was 36.6% and 65.9% for the itraconazole-treated group and 92.8% and 98.8% for the terbinafine-treated group. Itraconazole and terbinafine were both effective for the treatment of dermatophytosis affecting hedgehogs; however, terbinafine was more effective. © 2016 ESVD and ACVD.

  15. Membrane topology of hedgehog acyltransferase.

    Science.gov (United States)

    Matevossian, Armine; Resh, Marilyn D

    2015-01-23

    Hedgehog acyltransferase (Hhat) is a multipass transmembrane enzyme that mediates the covalent attachment of the 16-carbon fatty acid palmitate to the N-terminal cysteine of Sonic Hedgehog (Shh). Palmitoylation of Shh by Hhat is critical for short and long range signaling. Knowledge of the topological organization of Hhat transmembrane helices would enhance our understanding of Hhat-mediated Shh palmitoylation. Bioinformatics analysis of transmembrane domains within human Hhat using 10 different algorithms resulted in highly consistent predictions in the C-terminal, but not in the N-terminal, region of Hhat. To empirically determine the topology of Hhat, we designed and exploited Hhat constructs containing either terminal or 12 different internal epitope tags. We used selective permeabilization coupled with immunofluorescence as well as a protease protection assay to demonstrate that Hhat contains 10 transmembrane domains and 2 re-entrant loops. The invariant His and highly conserved Asp residues within the membrane-bound O-acyltransferase (MBOAT) homology domain are segregated on opposite sides of the endoplasmic reticulum membrane. The localization of His-379 on the lumenal membrane surface is consistent with a role for this invariant residue in catalysis. Analysis of the activity and stability of the Hhat constructs revealed that the C-terminal MBOAT domain is especially sensitive to manipulation. Moreover, there was remarkable similarity in the overall topological organization of Hhat and ghrelin O-acyltransferase, another MBOAT family member. Knowledge of the topological organization of Hhat could serve as an important tool for further design of selective Hhat inhibitors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. The long noncoding RNA TUG1 acts as a competing endogenous RNA to regulate the Hedgehog pathway by targeting miR-132 in hepatocellular carcinoma.

    Science.gov (United States)

    Li, Jingjing; Zhang, Qinghui; Fan, Xiaoming; Mo, Wenhui; Dai, Weiqi; Feng, Jiao; Wu, Liwei; Liu, Tong; Li, Sainan; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Yu, Qiang; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Xu, Ling; Guo, Chuanyong

    2017-09-12

    Emerging evidence shows that the Hedgehog pathway and the long noncoding RNA TUG1 play pivotal roles in cell proliferation, migration, and invasion in tumors. However, the mechanism underlying the effect of TUG1 and the Hedgehog pathway in hepatoma remains undefined. In the present study, we showed that the expression of TUG1 was negatively correlated with that of microRNA (miR)-132, and depletion of TUG1 inhibited the activation of the Hedgehog pathway in vitro and in vivo . We showed that TUG1 functions as a competing endogenous (ceRNA) by competing with miR-132 for binding to the sonic hedgehog protein in HCC, thereby suppressing the activation of Hedgehog signaling and its tumorigenic effect. These data indicate that targeting the TUG1-miR132-Hedgehog network could be a new strategy for the treatment of HCC.

  17. Reproductive characteristics of the african pygmy hedgehog, atelerix albiventris.

    Science.gov (United States)

    Bedford, J M; Mock, O B; Nagdas, S K; Winfrey, V P; Olson, G E

    2000-09-01

    To obtain further perspective on reproduction and particularly gamete function among so-called primitive mammals presently grouped in the Order Insectivora, we have examined the African hedgehog, Atelerix albiventris, in light of unusual features reported in shrews and moles. Atelerix proves to share many but not all of the characteristics seen in these other insectivores. The penis of Atelerix has a 'snail-like' form, but lacks the surface spines common in insectivores and a number of other mammals. Hedgehog spermatozoa display an eccentric insertion of the tail on the sperm head, and they manifest the barbs on the perforatorium that, in shrews, probably effect the initial binding of the sperm head to the zona pellucida. As a possible correlate, the structural matrix of the hedgehog acrosome comprises only two main components, as judged by immunoblotting, rather than the complex of peptides seen in the matrix of some higher mammals. The Fallopian tube of Atelerix is relatively simple; it displays only minor differences in width and in the arborized epithelium between the isthmus and ampulla, and shows no evidence of the unusual sperm crypts that characterize the isthmus or ampulla, depending on the species, in shrews and moles. In common with other insectivores, Atelerix appears to be an induced ovulator, as judged by the ovulation of some 6-8 eggs by about 23 h after injection of hCG. The dense cumulus oophorus appeared to have little matrix, in keeping with the modest dimensions of the tubal ampulla and, while it was not quite as discrete as that of soricids, it did show the same insensitivity to 0.5% (w/v) ovine or bovine hyaluronidase.

  18. The anatomy and histology of the atrioventricular conducting system in the hedgehog (Hemiechinus auritus) heart

    OpenAIRE

    NABIPOUR, Abolghasem

    2014-01-01

    This study examined the atrioventricular conducting system in 4 adult male hedgehogs (Hemiechinus auritus). The histological structure of these components was studied using routine histological methods. The AVN was located at the lower and anterior part of the interatrial septum, near the root of the aorta. It was almost oval and consisted of twisted cells. Internodal pathways in the hedgehog heart were not observed, but there were numerous purkinje-like fibers within the myocardium of the at...

  19. Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.

    Science.gov (United States)

    Bakshi, Anshika; Chaudhary, Sandeep C; Rana, Mehtab; Elmets, Craig A; Athar, Mohammad

    2017-12-01

    Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. © 2017 Wiley Periodicals, Inc.

  20. Precipitation kinetics of Mg-carbonates, influence of organic ligands and consequences for CO2 mineral sequestration

    International Nuclear Information System (INIS)

    Gautier, Q.

    2012-01-01

    Forming magnesium carbonate minerals through carbonation of magnesium silicates has been proposed as a safe and durable way to store carbon dioxide, with a possibly high potential to offset anthropogenic CO 2 emissions. To date however, chemical reactions involved in this process are facing strong kinetic limitations, which originate in the low reactivity of both Mg-silicates and Mg-carbonates. Numerous studies have focused on the dissolution of Mg-silicates, under the questionable hypothesis that this step limits the whole process. This thesis work focuses instead on the mechanisms and rates of formation of magnesium carbonates, which are the final products of carbonation reactions. The first part of the work is dedicated to studying the influence on magnesite precipitation kinetics of three organic ligands known to accelerate Mg-silicates dissolution rates: oxalate, citrate and EDTA. With help of mixed-flow reactor experiments performed between 100 and 150 C, we show that these ligands significantly reduce magnesite growth rates, through two combined mechanisms: (1) complexation of Mg 2+ cations in aqueous solution, which was rigorously estimated from a thermodynamic database established through a critical review of the literature, and (2) adsorption of ligands to a limited number of surface sites, leading to a decrease of the precipitation rate constant. The observed growth inhibition is maximal with citrate. We then used hydrothermal atomic force microscopy to probe the origin of the documented growth inhibition. Our observations show that citrate and oxalate interact with the crystal growth process on magnesite surface, modifying the shape of growth hillocks as well as the step generation frequency through spiral growth. We also show that the ligands adsorb preferentially on different kink-sites, which is probably related to their different structures and chemical properties. We propose that the stronger magnesite growth inhibition caused by citrate is related

  1. Hedgehog Signalling in the Embryonic Mouse Thymus

    Directory of Open Access Journals (Sweden)

    Alessandro Barbarulo

    2016-07-01

    Full Text Available 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.

  2. Indian Hedgehog Suppresses a Stromal Cell–Driven Intestinal Immune Response

    Directory of Open Access Journals (Sweden)

    B. Florien Westendorp

    2018-01-01

    Conclusions: We show that epithelium-derived Indian Hedgehog signals exclusively to fibroblasts in the intestine. Loss of Ihh leads to a rapid immune response with up-regulation of fibroblast-derived CXCL12, and migration of immune cells into the lamina propria.

  3. Indian Hedgehog Suppresses a Stromal Cell-Driven Intestinal Immune Response

    NARCIS (Netherlands)

    Westendorp, B. Florien; Büller, Nikè V. J. A.; Karpus, Olga N.; van Dop, Willemijn A.; Koster, Jan; Versteeg, Rogier; Koelink, Pim J.; Snel, Clinton Y.; Meisner, Sander; Roelofs, Joris J. T. H.; Uhmann, Anja; Ver Loren van Themaat, Emiel; Heijmans, Jarom; Hahn, Heidi; Muncan, Vanesa; Wildenberg, Manon E.; van den Brink, Gijs R.

    2018-01-01

    Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor

  4. Morpholoical Study of the Brandt’s Hedgehog, Paraechinus hypomelas (Eulipotyphla, Erinaceidae, Tongue

    Directory of Open Access Journals (Sweden)

    Goodarzi N.

    2016-10-01

    Full Text Available The morphology and histological structure of two adult Brandt’s hedgehog, Paraechinus hypomelas, (Brandt, 1836 tongue were examined by light and scanning electron microscopy. On the dorsal surface of the tongue, three types of papillae were observed: filiform, fungiform and vallate papillae. Apex and corpus of the tongue as well as the lateral surface of the corpus were covered with numerous filiform papillae with bifurcated tip, while the epithelium lining the ventral lingual surface was free from papillae. Discoid shape fungiform papillae were scattered over the entire surface of the lingual apex, corpus and lateral surface uniformly between the filiform ones without regional variation in number and size. Three elliptical or oval vallate papillae in an inverted triangle form were found on the root of the tongue. Each papilla had a lobulated and very irregular dorsal surface. Both fungiform and vallate papillae contain taste buds. The foliate papillae was absent. Overall, the present findings reveal that despite some similarities, the lingual papillae of the Brandt’s hedgehog as an omnivore animal has spices-specific characteristics compare to the Erinaceous auritus as an insectivore species. This finding provides a set of basic data about the morphology of tongue and its lingual papillae in Brandt’s hedgehog.

  5. Chrysotile dissolution rates: Implications for carbon sequestration

    International Nuclear Information System (INIS)

    Thom, James G.M.; Dipple, Gregory M.; Power, Ian M.; Harrison, Anna L.

    2013-01-01

    Highlights: • Uncertainties in serpentine dissolution kinetics hinder carbon sequestration models. • A pH dependent, far from equilibrium dissolution rate law for chrysotile. • F chrysotile (mol/m 2 /s) = 10 −0.21pH−10.57 at 22 °C over pH 2–10. • Laboratory dissolution rates consistent with mine waste weathering observations. • Potential for carbon sequestration in mine tailings and aquifers is assessed. - Abstract: Serpentine minerals (e.g., chrysotile) are a potentially important medium for sequestration of CO 2 via carbonation reactions. The goals of this study are to report a steady-state, far from equilibrium chrysotile dissolution rate law and to better define what role serpentine dissolution kinetics will have in constraining rates of carbon sequestration via serpentine carbonation. The steady-state dissolution rate of chrysotile in 0.1 m NaCl solutions was measured at 22 °C and pH ranging from 2 to 8. Dissolution experiments were performed in a continuously stirred flow-through reactor with the input solutions pre-equilibrated with atmospheric CO 2 . Both Mg and Si steady-state fluxes from the chrysotile surface, and the overall chrysotile flux were regressed and the following empirical relationships were obtained: F Mg =-0.22pH-10.02;F Si =-0.19pH-10.37;F chrysotile =-0.21pH-10.57 where F Mg , F Si , and F chrysotile are the log 10 Mg, Si, and molar chrysotile fluxes in mol/m 2 /s, respectively. Element fluxes were used in reaction-path calculations to constrain the rate of CO 2 sequestration in two geological environments that have been proposed as potential sinks for anthropogenic CO 2 . Carbon sequestration in chrysotile tailings at 10 °C is approximately an order of magnitude faster than carbon sequestration in a serpentinite-hosted aquifer at 60 °C on a per kilogram of water basis. A serpentinite-hosted aquifer, however, provides a larger sequestration capacity. The chrysotile dissolution rate law determined in this study has

  6. Foxf genes integrate tbx5 and hedgehog pathways in the second heart field for cardiac septation.

    Directory of Open Access Journals (Sweden)

    Andrew D Hoffmann

    2014-10-01

    Full Text Available The Second Heart Field (SHF has been implicated in several forms of congenital heart disease (CHD, including atrioventricular septal defects (AVSDs. Identifying the SHF gene regulatory networks required for atrioventricular septation is therefore an essential goal for understanding the molecular basis of AVSDs. We defined a SHF Hedgehog-dependent gene regulatory network using whole genome transcriptional profiling and GLI-chromatin interaction studies. The Forkhead box transcription factors Foxf1a and Foxf2 were identified as SHF Hedgehog targets. Compound haploinsufficiency for Foxf1a and Foxf2 caused atrioventricular septal defects, demonstrating the biological relevance of this regulatory network. We identified a Foxf1a cis-regulatory element that bound the Hedgehog transcriptional regulators GLI1 and GLI3 and the T-box transcription factor TBX5 in vivo. GLI1 and TBX5 synergistically activated transcription from this cis-regulatory element in vitro. This enhancer drove reproducible expression in vivo in the posterior SHF, the only region where Gli1 and Tbx5 expression overlaps. Our findings implicate Foxf genes in atrioventricular septation, describe the molecular underpinnings of the genetic interaction between Hedgehog signaling and Tbx5, and establish a molecular model for the selection of the SHF gene regulatory network for cardiac septation.

  7. Algae-Based Carbon Sequestration

    Science.gov (United States)

    Haoyang, Cai

    2018-03-01

    Our civilization is facing a series of environmental problems, including global warming and climate change, which are caused by the accumulation of green house gases in the atmosphere. This article will briefly analyze the current global warming problem and propose a method that we apply algae cultivation to absorb carbon and use shellfish to sequestrate it. Despite the importance of decreasing CO2 emissions or developing carbon-free energy sources, carbon sequestration should be a key issue, since the amount of carbon dioxide that already exists in the atmosphere is great enough to cause global warming. Algae cultivation would be a good choice because they have high metabolism rates and provides shellfish with abundant food that contains carbon. Shellfish’s shells, which are difficult to be decomposed, are reliable storage of carbon, compared to dead organisms like trees and algae. The amount of carbon that can be sequestrated by shellfish is considerable. However, the sequestrating rate of algae and shellfish is not high enough to affect the global climate. Research on algae and shellfish cultivation, including gene technology that aims to create “super plants” and “super shellfish”, is decisive to the solution. Perhaps the baton of history will shift to gene technology, from nuclear physics that has lost appropriate international environment after the end of the Cold War. Gene technology is vital to human survival.

  8. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  9. Hedgehog Signaling and Maintenance of Homeostasis in the Intestinal Epithelium

    NARCIS (Netherlands)

    Büller, Nikè V. J. A.; Rosekrans, Sanne L.; Westerlund, Jessica; van den Brink, Gijs R.

    2012-01-01

    Homeostasis of the rapidly renewing intestinal epithelium depends on a balance between cell proliferation and loss. Indian hedgehog (Ihh) acts as a negative feedback signal in this dynamic equilibrium. We discuss recent evidence that Ihh may be one of the key epithelial signals that indicates

  10. Learning to Play: A "Hedgehog Concept" for Physical Education

    Science.gov (United States)

    Johnson, Tyler

    2014-01-01

    What is physical education and why does it exist? Despite its relatively long and storied history, consensus about the main purpose of physical education remains minimal. This article explores three questions, developed by Jim Collins in his best-selling book Good to Great, to help organizations identify a hedgehog concept, or primary reason for…

  11. Hedgehog Signaling Inhibitors as Anti-Cancer Agents in Osteosarcoma

    International Nuclear Information System (INIS)

    Ram Kumar, Ram Mohan; Fuchs, Bruno

    2015-01-01

    Osteosarcoma is a rare type of cancer associated with a poor clinical outcome. Even though the pathologic characteristics of OS are well established, much remains to be understood, particularly at the molecular signaling level. The molecular mechanisms of osteosarcoma progression and metastases have not yet been fully elucidated and several evolutionary signaling pathways have been found to be linked with osteosarcoma pathogenesis, especially the hedgehog signaling (Hh) pathway. The present review will outline the importance and targeting the hedgehog signaling (Hh) pathway in osteosarcoma tumor biology. Available data also suggest that aberrant Hh signaling has pro-migratory effects and leads to the development of osteoblastic osteosarcoma. Activation of Hh signaling has been observed in osteosarcoma cell lines and also in primary human osteosarcoma specimens. Emerging data suggests that interference with Hh signal transduction by inhibitors may reduce osteosarcoma cell proliferation and tumor growth thereby preventing osteosarcomagenesis. From this perspective, we outline the current state of Hh pathway inhibitors in osteosarcoma. In summary, targeting Hh signaling by inhibitors promise to increase the efficacy of osteosarcoma treatment and improve patient outcome

  12. Studies on enhancing carbon sequestration in soils

    International Nuclear Information System (INIS)

    Marland, G.; Garten, C.T.; Post, W.M.; West, T.O.

    2004-01-01

    Studies of carbon and nitrogen dynamics in ecosystems are leading to an understanding of the factors and mechanisms that affect the inputs to and outputs from soils and how these might be manipulated to enhance C sequestration. Both the quantity and the quality of soil C inputs influence C storage and the potential for C sequestration. Changes in tillage intensity and crop rotations can also affect C sequestration by changing the soil physical and biological conditions and by changing the amounts and types of organic inputs to the soil. Analyses of changes in soil C and N balances are being supplemented with studies of the management practices needed to manage soil carbon and the implications for fossil-fuel use, emission of other greenhouse gases (such as N 2 O and CH 4 ), and impacts on agricultural productivity. The Consortium for Research on Enhancing Carbon Sequestration in Terrestrial Ecosystems (CSiTE) was created in 1999 to perform fundamental research that will lead to methods to enhance C sequestration as one component of a C management strategy. Research to date at one member of this consortium, Oak Ridge National Laboratory, has focused on C sequestration in soils and we begin here to draw together some of the results

  13. Epigenetic regulation of the Hedgehog and Wnt pathways in cancer

    NARCIS (Netherlands)

    Wils, Leon J.; Bijlsma, Maarten F.

    2018-01-01

    The Hedgehog (Hh) and wingless-Int1 (Wnt) pathways are important for tissue patterning in the developing embryo. In adult tissue, both pathways are typically dormant but are activated under certain conditions such as tissue damage. Aberrant activation of these pathways by mutations in key pathway

  14. Bmi1 is required for hedgehog pathway-driven medulloblastoma expansion

    NARCIS (Netherlands)

    Michael, Lowell Evan; Westerman, Bart A.; Ermilov, Alexandre N.; Wang, Aiqin; Ferris, Jennifer; Liu, Jianhong; Blom, Marleen; Ellison, David W.; van Lohuizen, Maarten; Dlugosz, Andrzej A.

    2008-01-01

    Inappropriate Hedgehog (Hh) signaling underlies development of a subset of medulloblastomas, and tumors with elevated HH signaling activity express the stem cell self-renewal gene BMI1. To test whether Bmi1 is required for Hh-driven medulloblastoma development, we varied Bmi1 gene dosage in

  15. Impact of the Smoothened inhibitor, IPI-926, on smoothened ciliary localization and Hedgehog pathway activity.

    Directory of Open Access Journals (Sweden)

    Marisa O Peluso

    Full Text Available A requisite step for canonical Hedgehog (Hh pathway activation by Sonic Hedgehog (Shh ligand is accumulation of Smoothened (Smo to the primary cilium (PC. Activation of the Hh pathway has been implicated in a broad range of cancers, and several Smo antagonists are being assessed clinically, one of which is approved for the treatment of advanced basal cell carcinoma. Recent reports demonstrate that various Smo antagonists differentially impact Smo localization to the PC while still exerting inhibitory activity. In contrast to other synthetic small molecule Smo antagonists, the natural product cyclopamine binds to and promotes ciliary accumulation of Smo and "primes" cells for Hh pathway hyper-responsiveness after compound withdrawal. We compared the properties of IPI-926, a semi-synthetic cyclopamine analog, to cyclopamine with regard to potency, ciliary Smo accumulation, and Hh pathway activity after compound withdrawal. Like cyclopamine, IPI-926 promoted accumulation of Smo to the PC. However, in contrast to cyclopamine, IPI-926 treatment did not prime cells for hyper-responsiveness to Shh stimulation after compound withdrawal, but instead demonstrated continuous inhibition of signaling. By comparing the levels of drug-induced ciliary Smo accumulation with the degree of Hh pathway activity after compound withdrawal, we propose that a critical threshold of ciliary Smo is necessary for "priming" activity to occur. This "priming" appears achievable with cyclopamine, but not IPI-926, and is cell-line dependent. Additionally, IPI-926 activity was evaluated in a murine tumor xenograft model and a pharmacokinetic/pharmacodynamic relationship was examined to assess for in vivo evidence of Hh pathway hyper-responsiveness. Plasma concentrations of IPI-926 correlated with the degree and duration of Hh pathway suppression, and pathway activity did not exceed baseline levels out to 96 hours post dose. The overall findings suggest that IPI-926 possesses

  16. ECONOMIC EVALUATION OF CO2 SEQUESTRATION TECHNOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    Bert R. Bock; Richard G. Rhudy; David E. Nichols

    2001-07-01

    In order to plan for potential CO{sub 2} mitigation mandates, utilities need better information on CO{sub 2} mitigation options, especially carbon sequestration options that involve non-utility operations. One of the major difficulties in evaluating CO{sub 2} sequestration technologies and practices, both geologic storage of captured CO{sub 2} and storage in biological sinks, is obtaining consistent, transparent, accurate, and comparable economics. This project is comparing the economics of major technologies and practices under development for CO{sub 2} sequestration, including captured CO{sub 2} storage options such as active oil reservoirs, depleted oil and gas reservoirs, deep aquifers, coal beds, and oceans, as well as the enhancement of biological sinks such as forests and croplands. An international group of experts has been assembled to compare on a consistent basis the economics of this diverse array of CO{sub 2} sequestration options. Designs and data collection are nearly complete for each of the CO{sub 2} sequestration options being compared. Initial spreadsheet development has begun on concepts involving storage of captured CO{sub 2}. No significant problems have been encountered, but some additional outside expertise will be accessed to supplement the team's expertise in the areas of life cycle analysis, oil and gas exploration and production, and comparing CO{sub 2} sequestration options that differ in timing and permanence of CO{sub 2} sequestration. Plans for the next reporting period are to complete data collection and a first approximation of the spreadsheet. We expect to complete this project on time and on budget.

  17. Equine cryptosporidial infection associated with Cryptosporidium hedgehog genotype in Algeria

    Czech Academy of Sciences Publication Activity Database

    Laatamna, A.E.; Wágnerová, P.; Sak, Bohumil; Květoňová, Dana; Aissi, M.; Rost, M.; Kváč, Martin

    2013-01-01

    Roč. 197, 1-2 (2013), s. 350-353 ISSN 0304-4017 Grant - others:GAJU(CZ) 022/2010/Z; GAJU(CZ) 011/2013/Z Institutional support: RVO:60077344 Keywords : horses * Cryptosporidium hedgehog genotype * PCR * SSU * GP60 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.545, year: 2013

  18. Southwest Regional Partnership on Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Brian McPherson

    2006-03-31

    The Southwest Partnership on Carbon Sequestration completed its Phase I program in December 2005. The main objective of the Southwest Partnership Phase I project was to evaluate and demonstrate the means for achieving an 18% reduction in carbon intensity by 2012. Many other goals were accomplished on the way to this objective, including (1) analysis of CO{sub 2} storage options in the region, including characterization of storage capacities and transportation options, (2) analysis and summary of CO{sub 2} sources, (3) analysis and summary of CO{sub 2} separation and capture technologies employed in the region, (4) evaluation and ranking of the most appropriate sequestration technologies for capture and storage of CO{sub 2} in the Southwest Region, (5) dissemination of existing regulatory/permitting requirements, and (6) assessing and initiating public knowledge and acceptance of possible sequestration approaches. Results of the Southwest Partnership's Phase I evaluation suggested that the most convenient and practical ''first opportunities'' for sequestration would lie along existing CO{sub 2} pipelines in the region. Action plans for six Phase II validation tests in the region were developed, with a portfolio that includes four geologic pilot tests distributed among Utah, New Mexico, and Texas. The Partnership will also conduct a regional terrestrial sequestration pilot program focusing on improved terrestrial MMV methods and reporting approaches specific for the Southwest region. The sixth and final validation test consists of a local-scale terrestrial pilot involving restoration of riparian lands for sequestration purposes. The validation test will use desalinated waters produced from one of the geologic pilot tests. The Southwest Regional Partnership comprises a large, diverse group of expert organizations and individuals specializing in carbon sequestration science and engineering, as well as public policy and outreach. These partners

  19. Dichotomy in Hedgehog Signaling between Human Healthy Vessel and Atherosclerotic Plaques

    NARCIS (Netherlands)

    Queiroz, Karla C. S.; Bijlsma, Maarten F.; Tio, René A.; Zeebregts, Clark J.; Dunaeva, Marina; Ferreira, Carmen V.; Fuhler, Gwenny M.; Kuipers, Ernst J.; Alves, Maria M.; Rezaee, Farhad; Spek, C. Arnold; Peppelenbosch, Maikel P.

    2012-01-01

    The major cause for plaque instability in atherosclerotic disease is neoangiogenic revascularization, but the factors controlling this process remain only partly understood. Hedgehog (HH) is a morphogen with important functions in revascularization, but its function in human healthy vessel biology

  20. Technological Development in Carbon Sequestration at Petrobras

    Energy Technology Data Exchange (ETDEWEB)

    Castello Branco, R.; Vazquez Sebastian, G.; Murce, T.; Cunha, P.; Dino, R.; Sartori Santarosa, C.

    2007-07-01

    Petrobras defined, in its mission, the intention to act in a safe and profitable way, with social and environmental responsibility. In its vision, the company decided to be an oil and energy company, taking into account climate change mitigation. These changes were partially caused, without the company's knowledge, for many years, by the burning of fossil fuels. Among many technologies available for this mitigation, carbon sequestration is the one that, in a short space of time, can avoid the collapse of earth's climate. In order to meet this carbon sequestration challenge, there has been established, at CENPES, three strategies for its technological development: (i) establishment of a Systemic Project for Carbon Sequestration within the scope of the Environmental Technology Program - PROAMB; (ii) creation of a Group of Carbon Sequestration Technologies for Climate Change Mitigation - formation of team and qualification program, which includes the realization of the International Seminar on Carbon Sequestration and Climate Change at Petrobras in October 2006; and (iii) Implementation of the Technological Network of Technologies for Climate Change Mitigation. (auth)

  1. Identification of conserved regions and residues within Hedgehog acyltransferase critical for palmitoylation of Sonic Hedgehog.

    Directory of Open Access Journals (Sweden)

    John A Buglino

    2010-06-01

    Full Text Available Sonic hedgehog (Shh is a palmitoylated protein that plays key roles in mammalian development and human cancers. Palmitoylation of Shh is required for effective long and short range Shh-mediated signaling. Attachment of palmitate to Shh is catalyzed by Hedgehog acyltransferase (Hhat, a member of the membrane bound O-acyl transferase (MBOAT family of multipass membrane proteins. The extremely hydrophobic composition of MBOAT proteins has limited their biochemical characterization. Except for mutagenesis of two conserved residues, there has been no structure-function analysis of Hhat, and the regions of the protein required for Shh palmitoylation are unknown.Here we undertake a systematic approach to identify residues within Hhat that are required for protein stability and/or enzymatic activity. We also identify a second, novel MBOAT homology region (residues 196-234 that is required for Hhat activity. In total, ten deletion mutants and eleven point mutants were generated and analyzed. Truncations at the N- and C-termini of Hhat yielded inactive proteins with reduced stability. Four Hhat mutants with deletions within predicted loop regions and five point mutants retained stability but lost palmitoylation activity. We purified two point mutants, W378A and H379A, with defective Hhat activity. Kinetic analyses revealed alterations in apparent K(m and V(max for Shh and/or palmitoyl CoA, changes that likely explain the catalytic defects observed for these mutants.This study has pinpointed specific regions and multiple residues that regulate Hhat stability and catalysis. Our findings should be applicable to other MBOAT proteins that mediate lipid modification of Wnt proteins and ghrelin, and should serve as a model for understanding how secreted morphogens are modified by palmitoyl acyltransferases.

  2. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels

    Science.gov (United States)

    Ma, Gang; Yu, Jiang; Xiao, Yue; Chan, Danny; Gao, Bo; Hu, Jianxin; He, Yongxing; Guo, Shengzhen; Zhou, Jian; Zhang, Lingling; Gao, Linghan; Zhang, Wenjuan; Kang, Yan; Cheah, Kathryn SE; Feng, Guoyin; Guo, Xizhi; Wang, Yujiong; Zhou, Cong-zhao; He, Lin

    2011-01-01

    Brachydactyly type A1 (BDA1), the first recorded Mendelian autosomal dominant disorder in humans, is characterized by a shortening or absence of the middle phalanges. Heterozygous missense mutations in the Indian Hedgehog (IHH) gene have been identified as a cause of BDA1; however, the biochemical consequences of these mutations are unclear. In this paper, we analyzed three BDA1 mutations (E95K, D100E, and E131K) in the N-terminal fragment of Indian Hedgehog (IhhN). Structural analysis showed that the E95K mutation changes a negatively charged area to a positively charged area in a calcium-binding groove, and that the D100E mutation changes the local tertiary structure. Furthermore, we showed that the E95K and D100E mutations led to a temperature-sensitive and calcium-dependent instability of IhhN, which might contribute to an enhanced intracellular degradation of the mutant proteins via the lysosome. Notably, all three mutations affected Hh binding to the receptor Patched1 (PTC1), reducing its capacity to induce cellular differentiation. We propose that these are common features of the mutations that cause BDA1, affecting the Hh tertiary structure, intracellular fate, binding to the receptor/partners, and binding to extracellular components. The combination of these features alters signaling capacity and range, but the impact is likely to be variable and mutation-dependent. The potential variation in the signaling range is characterized by an enhanced interaction with heparan sulfate for IHH with the E95K mutation, but not the E131K mutation. Taken together, our results suggest that these IHH mutations affect Hh signaling at multiple levels, causing abnormal bone development and abnormal digit formation. PMID:21537345

  3. Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling

    Science.gov (United States)

    Makrythanasis, Periklis; Bernard, Pascal; Kurosaka, Hiroshi; Vannier, Anne; Thauvin-Robinet, Christel; Borel, Christelle; Mazaud-Guittot, Séverine; Rolland, Antoine; Desdoits-Lethimonier, Christèle; Guipponi, Michel; Zimmermann, Céline; Stévant, Isabelle; Kuhne, Françoise; Conne, Béatrice; Santoni, Federico; Lambert, Sandy; Huet, Frederic; Mugneret, Francine; Jaruzelska, Jadwiga; Faivre, Laurence; Wilhelm, Dagmar; Jégou, Bernard; Trainor, Paul A.; Resh, Marilyn D.; Antonarakis, Stylianos E.; Nef, Serge

    2014-01-01

    The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development. PMID:24784881

  4. Simultaneous sequestration of uranyl and arsenate at the goethite/water interface

    International Nuclear Information System (INIS)

    Fang Yuan; Yawen Cai; Shitong Yang; Zhiyong Liu; Lanhua Chen; Yue Lang; Shuao Wang; Xiangke Wang; Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou; North China Electric Power University, Beijing

    2017-01-01

    This study highlights the simultaneous sequestration of U(VI) and arsenate at the goethite/water interface. The uptake trends and speciation of these two components were related with molar arsenate/U(VI) ratio, solution pH, contact order and aging time. A metastable [UO_2(H_2AsO_4)_2·H_2O] was observed after 3 days and then this solid completely transformed into Na_2(UO_2AsO_4)_2·3H_2O after 7 days. The disodium ethylenediamine tetraacetate ligand gave rise to the complete dissolution of Na_2(UO_2AsO_4)_2·3H_2O phase and the release of U(VI) and arsenate back into the solution. The experimental findings facilitated us better comprehend the migration and fate of coexisting U(VI) and arsenate in the aquatic environment. (author)

  5. Cryptosporidium erinacei and C. parvum in a group of overwintering hedgehogs

    Czech Academy of Sciences Publication Activity Database

    Hofmannová, L.; Hauptman, K.; Huclová, K.; Květoňová, Dana; Sak, Bohumil; Kváč, Martin

    2016-01-01

    Roč. 56, č. 1 (2016), s. 15-20 ISSN 0932-4739 R&D Projects: GA ČR GA15-01090S Institutional support: RVO:60077344 Keywords : Cryptosporidiosis * Erinaceus europaeus * European hedgehog Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.581, year: 2016

  6. LncRNA EGOT Promotes Tumorigenesis Via Hedgehog Pathway in Gastric Cancer.

    Science.gov (United States)

    Peng, Wei; Wu, Jianzhong; Fan, Hong; Lu, Jianwei; Feng, Jifeng

    2017-12-05

    Gastric cancer (GC) is one of the mostly terminal malignancies with poor prognosis. Long noncoding RNA EGOT (EGOT) acts as a crucial regulator in the breast cancer. However, the function of EGOT in GC remains unknown. This work was to explore the clinical value and biological significance of EGOT in GC. EGOT levels in GC tissue and cell were analyzed by qRT-PCR. After knockdown of EGOT, GC cell growth and cycle progression were detected. The expression of EGOT was observably elevated in GC. Upregulation of EGOT was related with lymphatic metastasis and TNM stage. In addition, knockdown of EGOT by siRNA could significantly inhibit GC cell proliferation and arrest cycle progression in G1 phase. Moreover, EGOT mediated cyclin D1 expression in GC cells which was regulated by Hedgehog pathway. Further, loss of EGOT downregulated Hedgehog signaling pathway in GC cells. EGOT functions as an oncogene in GC, and may be useful as a conceivable diagnostic and prognostic biomarker for GC tumorigenesis.

  7. Non-destructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): II. Hair and spines as indicators of endogenous metal and As concentrations

    International Nuclear Information System (INIS)

    D'Have, Helga; Scheirs, Jan; Mubiana, Valentine Kayawe; Verhagen, Ron; Blust, Ronny; Coen, Wim de

    2006-01-01

    The role of hair and spines of the European hedgehog as non-destructive monitoring tools of metal (Ag, Al, Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn) and As pollution in terrestrial ecosystems was investigated. Our results showed that mean pollution levels of a random sample of hedgehogs in Flanders are low to moderate. Yet, individual hedgehogs may be at risk for metal toxicity. Tissue distribution analyses (hair, spines, liver, kidney, muscle and fat tissue) indicated that metals and As may reach considerable concentrations in external tissues, such as hair and spines. Positive relationships were observed between concentrations in hair and those in liver, kidney and muscle for Al, Co, Cr, Cu, and Pb (0.43 < r < 0.85). Spine concentrations were positively related to liver, kidney and muscle concentrations for Cd, Co, Cr, Cu and Pb (0.37 < r < 0.62). Hair Ag, As, Fe and Zn and spine Ag, Al, As and Fe were related to metal concentrations in one or two of the investigated internal tissues (0.31 < r < 0.45). The regression models presented here may be used to predict metal and As concentrations in internal tissues of hedgehogs when concentrations in hair or spines are available. The present study demonstrated the possibility of using hair and spines for non-destructive monitoring of metal and As pollution in hedgehogs. - Hedgehog hair and spines are promising non-destructive biomonitoring tools of terrestrial metal pollution

  8. Non-destructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): II. Hair and spines as indicators of endogenous metal and As concentrations

    Energy Technology Data Exchange (ETDEWEB)

    D' Have, Helga [Ecophysiology, Biochemistry and Toxicology Group, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)]. E-mail: helga.dhave@ua.ac.be; Scheirs, Jan [Evolutionary Biology Group, Department of Biology, University of Antwerp, B-2020 Antwerp (Belgium); Mubiana, Valentine Kayawe [Ecophysiology, Biochemistry and Toxicology Group, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Verhagen, Ron [Evolutionary Biology Group, Department of Biology, University of Antwerp, B-2020 Antwerp (Belgium); Blust, Ronny [Ecophysiology, Biochemistry and Toxicology Group, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Coen, Wim de [Ecophysiology, Biochemistry and Toxicology Group, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)

    2006-08-15

    The role of hair and spines of the European hedgehog as non-destructive monitoring tools of metal (Ag, Al, Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn) and As pollution in terrestrial ecosystems was investigated. Our results showed that mean pollution levels of a random sample of hedgehogs in Flanders are low to moderate. Yet, individual hedgehogs may be at risk for metal toxicity. Tissue distribution analyses (hair, spines, liver, kidney, muscle and fat tissue) indicated that metals and As may reach considerable concentrations in external tissues, such as hair and spines. Positive relationships were observed between concentrations in hair and those in liver, kidney and muscle for Al, Co, Cr, Cu, and Pb (0.43 < r < 0.85). Spine concentrations were positively related to liver, kidney and muscle concentrations for Cd, Co, Cr, Cu and Pb (0.37 < r < 0.62). Hair Ag, As, Fe and Zn and spine Ag, Al, As and Fe were related to metal concentrations in one or two of the investigated internal tissues (0.31 < r < 0.45). The regression models presented here may be used to predict metal and As concentrations in internal tissues of hedgehogs when concentrations in hair or spines are available. The present study demonstrated the possibility of using hair and spines for non-destructive monitoring of metal and As pollution in hedgehogs. - Hedgehog hair and spines are promising non-destructive biomonitoring tools of terrestrial metal pollution.

  9. Non-destructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): II. Hair and spines as indicators of endogenous metal and As concentrations.

    Science.gov (United States)

    D'Havé, Helga; Scheirs, Jan; Mubiana, Valentine Kayawe; Verhagen, Ron; Blust, Ronny; De Coen, Wim

    2006-08-01

    The role of hair and spines of the European hedgehog as non-destructive monitoring tools of metal (Ag, Al, Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn) and As pollution in terrestrial ecosystems was investigated. Our results showed that mean pollution levels of a random sample of hedgehogs in Flanders are low to moderate. Yet, individual hedgehogs may be at risk for metal toxicity. Tissue distribution analyses (hair, spines, liver, kidney, muscle and fat tissue) indicated that metals and As may reach considerable concentrations in external tissues, such as hair and spines. Positive relationships were observed between concentrations in hair and those in liver, kidney and muscle for Al, Co, Cr, Cu, and Pb (0.43 Spine concentrations were positively related to liver, kidney and muscle concentrations for Cd, Co, Cr, Cu and Pb (0.37 spine Ag, Al, As and Fe were related to metal concentrations in one or two of the investigated internal tissues (0.31 hedgehogs when concentrations in hair or spines are available. The present study demonstrated the possibility of using hair and spines for non-destructive monitoring of metal and As pollution in hedgehogs.

  10. An Overview of Geologic Carbon Sequestration Potential in California

    Energy Technology Data Exchange (ETDEWEB)

    Cameron Downey; John Clinkenbeard

    2005-10-01

    As part of the West Coast Regional Carbon Sequestration Partnership (WESTCARB), the California Geological Survey (CGS) conducted an assessment of geologic carbon sequestration potential in California. An inventory of sedimentary basins was screened for preliminary suitability for carbon sequestration. Criteria included porous and permeable strata, seals, and depth sufficient for critical state carbon dioxide (CO{sub 2}) injection. Of 104 basins inventoried, 27 met the criteria for further assessment. Petrophysical and fluid data from oil and gas reservoirs was used to characterize both saline aquifers and hydrocarbon reservoirs. Where available, well log or geophysical information was used to prepare basin-wide maps showing depth-to-basement and gross sand distribution. California's Cenozoic marine basins were determined to possess the most potential for geologic sequestration. These basins contain thick sedimentary sections, multiple saline aquifers and oil and gas reservoirs, widespread shale seals, and significant petrophysical data from oil and gas operations. Potential sequestration areas include the San Joaquin, Sacramento, Ventura, Los Angeles, and Eel River basins, followed by the smaller Salinas, La Honda, Cuyama, Livermore, Orinda, and Sonoma marine basins. California's terrestrial basins are generally too shallow for carbon sequestration. However, the Salton Trough and several smaller basins may offer opportunities for localized carbon sequestration.

  11. ECONOMIC EVALUATION OF CO2 SEQUESTRATION TECHNOLOGIES; SEMIANNUAL

    International Nuclear Information System (INIS)

    Bert R. Bock; Richard G. Rhudy; David E. Nichols

    2001-01-01

    In order to plan for potential CO(sub 2) mitigation mandates, utilities need better information on CO(sub 2) mitigation options, especially carbon sequestration options that involve non-utility operations. One of the major difficulties in evaluating CO(sub 2) sequestration technologies and practices, both geologic storage of captured CO(sub 2) and storage in biological sinks, is obtaining consistent, transparent, accurate, and comparable economics. This project is comparing the economics of major technologies and practices under development for CO(sub 2) sequestration, including captured CO(sub 2) storage options such as active oil reservoirs, depleted oil and gas reservoirs, deep aquifers, coal beds, and oceans, as well as the enhancement of biological sinks such as forests and croplands. An international group of experts has been assembled to compare on a consistent basis the economics of this diverse array of CO(sub 2) sequestration options. Designs and data collection are nearly complete for each of the CO(sub 2) sequestration options being compared. Initial spreadsheet development has begun on concepts involving storage of captured CO(sub 2). No significant problems have been encountered, but some additional outside expertise will be accessed to supplement the team's expertise in the areas of life cycle analysis, oil and gas exploration and production, and comparing CO(sub 2) sequestration options that differ in timing and permanence of CO(sub 2) sequestration. Plans for the next reporting period are to complete data collection and a first approximation of the spreadsheet. We expect to complete this project on time and on budget

  12. Novel hedgehog-like 5 V LiCoPO4 positive electrode material for rechargeable lithium battery

    Science.gov (United States)

    Wang, Fei; Yang, Jun; NuLi, Yanna; Wang, Jiulin

    2011-05-01

    Hedgehog-like LiCoPO4 with hierarchical microstructures is first synthesized via a simple solvothermal process in water-benzyl alcohol mixed solvent at 200 °C. Morphology and crystalline structure of the samples are characterized by scanning electron microscope, transmission electron microscopy and X-ray diffraction. The hedgehog-like LiCoPO4 microstructures in the size of about 5-8 μm are composed of large numbers of nanorods in diameter of ca. 40 nm and length of ca. 1 μm, which are coated with a carbon layer of ca. 8 nm in thickness by in situ carbonization of glucose during the solvothermal reaction. As a 5 V positive electrode material for rechargeable lithium battery, the hedgehog-like LiCoPO4 delivers an initial discharge capacity of 136 mAh g-1 at 0.1 C rate and retains its 91% after 50 cycles, showing much better electrochemical performances than sub-micrometer LiCoPO4 synthesized by conventional high-temperature solid-state reaction.

  13. TEST and EVALUATION REPORT FOR THE HEDGEHOG-II PACKAGING SYSTEMS DOT-7A TYPE A CONTAINER

    International Nuclear Information System (INIS)

    KELLY, D.L.

    2003-01-01

    This report documents the US. Department of Transportation Specification 7A (DOT-7A) Type A compliance test and evaluation results for the Hedgehog-II packaging systems. The approved Hedgehog-II packaging configurations provide primary and secondary containment. The approved packaging configurations described within this report are designed to ship Type A quantities of radioactive materials, normal form. Contents may be in solid or liquid form. Liquids transported in the approved 1 L glass bottle assembly shall have a specific gravity of less than or equal to 1.6. Liquids transported in all other approved configurations shall have a specific gravity of less than or equal to 2.0. The solid contents, including packaging, are limited in weight to the gross weight of the as-tested liquids and bottles. The approved Hedgehog-II packaging configurations described in this report may be transported by air, and have been evaluated as meeting the applicable International Air Transport Association/International Civil Aviation Organization (IATA/ICAO) Dangerous Goods Regulations in addition to the DOT requirements

  14. Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization.

    Science.gov (United States)

    Courtaut, Flavie; Derangère, Valentin; Chevriaux, Angélique; Ladoire, Sylvain; Cotte, Alexia K; Arnould, Laurent; Boidot, Romain; Rialland, Mickaël; Ghiringhelli, François; Rébé, Cédric

    2015-09-29

    Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXRβ-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXRβ. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXRβ with the truncated form of RXRα (t-RXRα) was responsible for the sequestration of LXRβ in the cytoplasm in colon cancer cells. Moreover t-RXRα was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXRβ and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXRβ, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXRβ could be a promising target in cancer therapy.

  15. Federal Control of Geological Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Reitze, Arnold W. [Univ. of Utah, Salt Lake City, UT (United States)

    2011-04-01

    The United States has economically recoverable coal reserves of about 261 billion tons, which is in excess of a 250-­year supply based on 2009 consumption rates. However, in the near future the use of coal may be legally restricted because of concerns over the effects of its combustion on atmospheric carbon dioxide concentrations. In response, the U.S. Department of Energy is making significant efforts to help develop and implement a commercial scale program of geologic carbon sequestration that involves capturing and storing carbon dioxide emitted from coal-burning electric power plants in deep underground formations. This article explores the technical and legal problems that must be resolved in order to have a viable carbon sequestration program. It covers the responsibilities of the United States Environmental Protection Agency and the Departments of Energy, Transportation and Interior. It discusses the use of the Safe Drinking Water Act, the Clean Air Act, the National Environmental Policy Act, the Endangered Species Act, and other applicable federal laws. Finally, it discusses the provisions related to carbon sequestration that have been included in the major bills dealing with climate change that Congress has been considering in 2009 and 2010. The article concludes that the many legal issues that exist can be resolved, but whether carbon sequestration becomes a commercial reality will depend on reducing its costs or by imposing legal requirements on fossil-fired power plants that result in the costs of carbon emissions increasing to the point that carbon sequestration becomes a feasible option.

  16. Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.

    Science.gov (United States)

    Cloutier, Nathalie; Allaeys, Isabelle; Marcoux, Genevieve; Machlus, Kellie R; Mailhot, Benoit; Zufferey, Anne; Levesque, Tania; Becker, Yann; Tessandier, Nicolas; Melki, Imene; Zhi, Huiying; Poirier, Guy; Rondina, Matthew T; Italiano, Joseph E; Flamand, Louis; McKenzie, Steven E; Cote, Francine; Nieswandt, Bernhard; Khan, Waliul I; Flick, Matthew J; Newman, Peter J; Lacroix, Steve; Fortin, Paul R; Boilard, Eric

    2018-02-13

    There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood-brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.

  17. Evolutionary genomics and adaptive evolution of the Hedgehog gene family (Shh, Ihh and Dhh in vertebrates.

    Directory of Open Access Journals (Sweden)

    Joana Pereira

    Full Text Available The Hedgehog (Hh gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog--Shh; Indian hedgehog--Ihh; and Desert hedgehog--Dhh, each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we used comparative genomic and adaptive evolutionary analyses to characterize the evolution of the Hh genes in vertebrates following the two major whole genome duplication (WGD events. To overcome the lack of Hh-coding sequences on avian publicly available databases, we used an extensive dataset of 45 avian and three non-avian reptilian genomes to show that birds have all three Hh paralogs. We find suggestions that following the WGD events, vertebrate Hh paralogous genes evolved independently within similar linkage groups and under different evolutionary rates, especially within the catalytic domain. The structural regions around the ion-binding site were identified to be under positive selection in the signaling domain. These findings contrast with those observed in invertebrates, where different lineages that experienced gene duplication retained similar selective constraints in the Hh orthologs. Our results provide new insights on the evolutionary history of the Hh gene family, the functional roles of these paralogs in vertebrate species, and on the location of mutational hotspots.

  18. Evolutionary genomics and adaptive evolution of the Hedgehog gene family (Shh, Ihh and Dhh) in vertebrates.

    Science.gov (United States)

    Pereira, Joana; Johnson, Warren E; O'Brien, Stephen J; Jarvis, Erich D; Zhang, Guojie; Gilbert, M Thomas P; Vasconcelos, Vitor; Antunes, Agostinho

    2014-01-01

    The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog--Shh; Indian hedgehog--Ihh; and Desert hedgehog--Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we used comparative genomic and adaptive evolutionary analyses to characterize the evolution of the Hh genes in vertebrates following the two major whole genome duplication (WGD) events. To overcome the lack of Hh-coding sequences on avian publicly available databases, we used an extensive dataset of 45 avian and three non-avian reptilian genomes to show that birds have all three Hh paralogs. We find suggestions that following the WGD events, vertebrate Hh paralogous genes evolved independently within similar linkage groups and under different evolutionary rates, especially within the catalytic domain. The structural regions around the ion-binding site were identified to be under positive selection in the signaling domain. These findings contrast with those observed in invertebrates, where different lineages that experienced gene duplication retained similar selective constraints in the Hh orthologs. Our results provide new insights on the evolutionary history of the Hh gene family, the functional roles of these paralogs in vertebrate species, and on the location of mutational hotspots.

  19. Big Sky Carbon Sequestration Partnership

    Energy Technology Data Exchange (ETDEWEB)

    Susan Capalbo

    2005-12-31

    The Big Sky Carbon Sequestration Partnership, led by Montana State University, is comprised of research institutions, public entities and private sectors organizations, and the Confederated Salish and Kootenai Tribes and the Nez Perce Tribe. Efforts under this Partnership in Phase I are organized into four areas: (1) Evaluation of sources and carbon sequestration sinks that will be used to determine the location of pilot demonstrations in Phase II; (2) Development of GIS-based reporting framework that links with national networks; (3) Design of an integrated suite of monitoring, measuring, and verification technologies, market-based opportunities for carbon management, and an economic/risk assessment framework; (referred to below as the Advanced Concepts component of the Phase I efforts) and (4) Initiation of a comprehensive education and outreach program. As a result of the Phase I activities, the groundwork is in place to provide an assessment of storage capabilities for CO{sub 2} utilizing the resources found in the Partnership region (both geological and terrestrial sinks), that complements the ongoing DOE research agenda in Carbon Sequestration. The geology of the Big Sky Carbon Sequestration Partnership Region is favorable for the potential sequestration of enormous volume of CO{sub 2}. The United States Geological Survey (USGS 1995) identified 10 geologic provinces and 111 plays in the region. These provinces and plays include both sedimentary rock types characteristic of oil, gas, and coal productions as well as large areas of mafic volcanic rocks. Of the 10 provinces and 111 plays, 1 province and 4 plays are located within Idaho. The remaining 9 provinces and 107 plays are dominated by sedimentary rocks and located in the states of Montana and Wyoming. The potential sequestration capacity of the 9 sedimentary provinces within the region ranges from 25,000 to almost 900,000 million metric tons of CO{sub 2}. Overall every sedimentary formation investigated

  20. Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice

    NARCIS (Netherlands)

    Büller, Nikè V J A; Rosekrans, Sanne L.; Metcalfe, Ciara; Heijmans, Jarom; Van Dop, Willemijn A.; Fessler, Evelyn; Jansen, Marnix; Ahn, Christina; Vermeulen, Jacqueline L M; Westendorp, B. Florien; Robanus-Maandag, Els C.; Offerhaus, G. Johan; Medema, Jan Paul; D'Haens, Geert R A M; Wildenberg, Manon E.; De Sauvage, Frederic J.; Muncan, Vanesa; Van Den Brink, Gijs R.

    2015-01-01

    BACKGROUND & AIMS: Indian hedgehog (IHH) is an epithelial-derived signal in the intestinal stroma, inducing factors that restrict epithelial proliferation and suppress activation of the immune system. In addition to these rapid effects of IHH signaling, IHH is required to maintain a stromal

  1. Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals.

    Science.gov (United States)

    Corallo, Diana; Schiavinato, Alvise; Trapani, Valeria; Moro, Enrico; Argenton, Francesco; Bonaldo, Paolo

    2013-11-01

    The notochord is a transient and essential structure that provides both mechanical and signaling cues to the developing vertebrate embryo. In teleosts, the notochord is composed of a core of large vacuolated cells and an outer layer of cells that secrete the notochord sheath. In this work, we have identified the extracellular matrix glycoprotein Emilin3 as a novel essential component of the zebrafish notochord sheath. The development of the notochord sheath is impaired in Emilin3 knockdown embryos. The patterning activity of the notochord is also affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2 in the notochord sheath. Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked.

  2. Big Sky Carbon Sequestration Partnership

    Energy Technology Data Exchange (ETDEWEB)

    Susan M. Capalbo

    2005-11-01

    The Big Sky Carbon Sequestration Partnership, led by Montana State University, is comprised of research institutions, public entities and private sectors organizations, and the Confederated Salish and Kootenai Tribes and the Nez Perce Tribe. Efforts under this Partnership in Phase I fall into four areas: evaluation of sources and carbon sequestration sinks that will be used to determine the location of pilot demonstrations in Phase II; development of GIS-based reporting framework that links with national networks; designing an integrated suite of monitoring, measuring, and verification technologies and assessment frameworks; and initiating a comprehensive education and outreach program. The groundwork is in place to provide an assessment of storage capabilities for CO2 utilizing the resources found in the Partnership region (both geological and terrestrial sinks), that would complement the ongoing DOE research agenda in Carbon Sequestration. The region has a diverse array of geological formations that could provide storage options for carbon in one or more of its three states. Likewise, initial estimates of terrestrial sinks indicate a vast potential for increasing and maintaining soil C on forested, agricultural, and reclaimed lands. Both options include the potential for offsetting economic benefits to industry and society. Steps have been taken to assure that the GIS-based framework is consistent among types of sinks within the Big Sky Partnership area and with the efforts of other DOE regional partnerships. The Partnership recognizes the critical importance of measurement, monitoring, and verification technologies to support not only carbon trading but all policies and programs that DOE and other agencies may want to pursue in support of GHG mitigation. The efforts in developing and implementing MMV technologies for geological sequestration reflect this concern. Research is also underway to identify and validate best management practices for soil C in the

  3. Hedgehog signaling pathway in neuroblastoma differentiation.

    Science.gov (United States)

    Souzaki, Ryota; Tajiri, Tatsuro; Souzaki, Masae; Kinoshita, Yoshiaki; Tanaka, Sakura; Kohashi, Kenichi; Oda, Yoshinao; Katano, Mitsuo; Taguchi, Tomoaki

    2010-12-01

    The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 ganglioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P ≦ .01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P = .015). Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. PV water pumping for carbon sequestration in dry land agriculture

    International Nuclear Information System (INIS)

    Olsson, Alexander; Campana, Pietro Elia; Lind, Mårten; Yan, Jinyue

    2015-01-01

    Highlights: • A novel model for carbon sequestration in dry land agriculture is developed. • We consider the water-food-energy-climate nexus to assess carbon sequestration. • Using water for carbon sequestration should be assessed critically. • Co-benefits of carbon sequestration should be included in the assessment. • Moisture feedback is part of the nexus model. - Abstract: This paper suggests a novel model for analysing carbon sequestration activities in dry land agriculture considering the water-food-energy-climate nexus. The paper is based on our on-going studies on photovoltaic water pumping (PVWP) systems for irrigation of grasslands in China. Two carbon sequestration projects are analysed in terms of their water productivity and carbon sequestration potential. It is concluded that the economic water productivity, i.e. how much water that is needed to produce an amount of grass, of grassland restoration is low and that there is a need to include several of the other co-benefits to justify the use of water for climate change mitigation. The co-benefits are illustrated in a nexus model including (1) climate change mitigation, (2) water availability, (3) downstream water impact, (4) energy security, (5) food security and (6) moisture recycling. We argue for a broad approach when analysing water for carbon sequestration. The model includes energy security and food security together with local and global water concerns. This makes analyses of dry land carbon sequestration activities more relevant and accurate. Without the nexus approach, the co-benefits of grassland restoration tend to be diminished

  5. Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation.

    Science.gov (United States)

    Outram, Susan V; Hager-Theodorides, Ariadne L; Shah, Divya K; Rowbotham, Nicola J; Drakopoulou, Ekati; Ross, Susan E; Lanske, Beate; Dessens, Johannes T; Crompton, Tessa

    2009-03-05

    We show that Indian Hedgehog (Ihh) regulates T-cell development and homeostasis in both fetal and adult thymus, controlling thymocyte number. Fetal Ihh(-/-) thymi had reduced differentiation to double-positive (DP) cell and reduced cell numbers compared with wild-type littermates. Surprisingly, fetal Ihh(+/-) thymi had increased thymocyte numbers and proportion of DP cells relative to wild type, indicating that Ihh also negatively regulates thymocyte development. In vitro treatment of thymus explants with exogenous recombinant Hedgehog protein promoted thymocyte development in Ihh(-/-) thymi but inhibited thymocyte development in Ihh(+/-), confirming both positive and negative regulatory functions of Ihh. Analysis of Rag(-/-)Ihh(+/-) thymi showed that Ihh promotes T-cell development before pre-T-cell receptor (pre-TCR) signaling, but negatively regulates T-cell development only after pre-TCR signaling has taken place. We show that Ihh is most highly expressed by the DP population and that Ihh produced by DP cells feeds back to negatively regulate the differentiation and proliferation of their double-negative progenitors. Thus, differentiation from double-negative to DP cell, and hence the size of the DP population, is dependent on the concentration of Ihh in the thymus. Analysis of Ihh conditional knockout and heterozygote adult mice showed that Ihh also influences thymocyte number in the adult.

  6. Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice

    NARCIS (Netherlands)

    Büller, Nikè V. J. A.; Rosekrans, Sanne L.; Metcalfe, Ciara; Heijmans, Jarom; van Dop, Willemijn A.; Fessler, Evelyn; Jansen, Marnix; Ahn, Christina; Vermeulen, Jacqueline L. M.; Westendorp, B. Florien; Robanus-Maandag, Els C.; Offerhaus, G. Johan; Medema, Jan Paul; D'Haens, Geert R. A. M.; Wildenberg, Manon E.; de Sauvage, Frederic J.; Muncan, Vanesa; van den Brink, Gijs R.

    2015-01-01

    Indian hedgehog (IHH) is an epithelial-derived signal in the intestinal stroma, inducing factors that restrict epithelial proliferation and suppress activation of the immune system. In addition to these rapid effects of IHH signaling, IHH is required to maintain a stromal phenotype in which

  7. Mechanisms of Soil Carbon Sequestration

    Science.gov (United States)

    Lal, Rattan

    2015-04-01

    Carbon (C) sequestration in soil is one of the several strategies of reducing the net emission of CO2 into the atmosphere. Of the two components, soil organic C (SOC) and soil inorganic C (SIC), SOC is an important control of edaphic properties and processes. In addition to off-setting part of the anthropogenic emissions, enhancing SOC concentration to above the threshold level (~1.5-2.0%) in the root zone has numerous ancillary benefits including food and nutritional security, biodiversity, water quality, among others. Because of its critical importance in human wellbeing and nature conservancy, scientific processes must be sufficiently understood with regards to: i) the potential attainable, and actual sink capacity of SOC and SIC, ii) permanence of the C sequestered its turnover and mean residence time, iii) the amount of biomass C needed (Mg/ha/yr) to maintain and enhance SOC pool, and to create a positive C budget, iv) factors governing the depth distribution of SOC, v) physical, chemical and biological mechanisms affecting the rate of decomposition by biotic and abiotic processes, vi) role of soil aggregation in sequestration and protection of SOC and SIC pool, vii) the importance of root system and its exudates in transfer of biomass-C into the SOC pools, viii) significance of biogenic processes in formation of secondary carbonates, ix) the role of dissolved organic C (DOC) in sequestration of SOC and SIC, and x) importance of weathering of alumino-silicates (e.g., powered olivine) in SIC sequestration. Lack of understanding of these and other basic processes leads to misunderstanding, inconsistencies in interpretation of empirical data, and futile debates. Identification of site-specific management practices is also facilitated by understanding of the basic processes of sequestration of SOC and SIC. Sustainable intensification of agroecosystems -- producing more from less by enhancing the use efficiency and reducing losses of inputs, necessitates thorough

  8. Hurricane impacts on US forest carbon sequestration

    Science.gov (United States)

    Steven G. McNulty

    2002-01-01

    Recent focus has been given to US forests as a sink for increases in atmospheric carbon dioxide. Current estimates of US Forest carbon sequestration average approximately 20 Tg (i.e. 1012 g) year. However, predictions of forest carbon sequestration often do not include the influence of hurricanes on forest carbon storage. Intense hurricanes...

  9. Lithium inhibits tumorigenic potential of PDA cells through targeting hedgehog-GLI signaling pathway.

    Directory of Open Access Journals (Sweden)

    Zhonglu Peng

    Full Text Available Hedgehog signaling pathway plays a critical role in the initiation and development of pancreatic ductal adenocarcinoma (PDA and represents an attractive target for PDA treatment. Lithium, a clinical mood stabilizer for mental disorders, potently inhibits the activity of glycogen synthase kinase 3β (GSK3β that promotes the ubiquitin-dependent proteasome degradation of GLI1, an important downstream component of hedgehog signaling. Herein, we report that lithium inhibits cell proliferation, blocks G1/S cell-cycle progression, induces cell apoptosis and suppresses tumorigenic potential of PDA cells through down-regulation of the expression and activity of GLI1. Moreover, lithium synergistically enhances the anti-cancer effect of gemcitabine. These findings further our knowledge of mechanisms of action for lithium and provide a potentially new therapeutic strategy for PDA through targeting GLI1.

  10. Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development

    NARCIS (Netherlands)

    Kosinski, C.; Stange, D.E.; Xu, C.; Chan, A.S.; Ho, C.; Yuen, S.T.; Mifflin, R.C.; Powell, D.W.; Clevers, H.; Leung, S.Y.; Chen, X.N.

    2010-01-01

    BACKGROUND & AIMS: Intestinal stem cells (ISCs) are regulated by the mesenchymal environment via physical interaction and diffusible factors. We examined the role of Indian hedgehog (Ihh) in mesenchymal organization and the mechanisms by which perturbations in epithelial-mesenchymal interactions

  11. DOE Ocean Carbon Sequestration Research Workshop 2005

    Energy Technology Data Exchange (ETDEWEB)

    Sarmiento, Jorge L. [Princeton Univ., NJ (United States); Chavez, Francisco [Monterey Bay Aquarium Research Inst. (MBARI), Moss Landing, CA (United States); Maltrud, Matthew [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Adams, Eric [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Arrigo, Kevin [Stanford Univ., CA (United States). Dept. of Geophysics; Barry, James [Monterey Bay Aquarium Research Inst. (MBARI), Moss Landing, CA (United States); Carmen, Kevin [Louisiana State Univ., Baton Rouge, LA (United States); Bishop, James [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Bleck, Rainer [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gruber, Niki [Univ. of California, Los Angeles, CA (United States); Erickson, David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kennett, James [Univ. of California, Santa Barbara, CA (United States); Tsouris, Costas [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tagliabue, Alessandro [Lab. of Climate and Environmental Sciences (LSCE), Gif-sur-Yvette (France); Paytan, Adina [Stanford Univ., CA (United States); Repeta, Daniel [Woods Hole Oceanographic Inst. (WHOI), Woods Hole, MA (United States); Yager, Patricia L. [Univ. of Georgia, Athens, GA (United States); Marshall, John [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Gnanadesikan, Anand [Geophysical Fluid Dynamics Lab. (GFDL), Princeton, NJ (United States)

    2007-01-11

    The purpose of this proposal was to fund a workshop to bring together the principal investigators of all the projects that were being funded under the DOE ocean carbon sequestration research program. The primary goal of the workshop was to interchange research results, to discuss ongoing research, and to identify future research priorities. In addition, we hoped to encourage the development of synergies and collaborations between the projects and to write an EOS article summarizing the results of the meeting. Appendix A summarizes the plan of the workshop as originally proposed, Appendix B lists all the principal investigators who were able to attend the workshop, Appendix C shows the meeting agenda, and Appendix D lists all the abstracts that were provided prior to the meeting. The primary outcome of the meeting was a decision to write two papers for the reviewed literature on carbon sequestration by iron fertilization, and on carbon sequestration by deep sea injection and to examine the possibility of an overview article in EOS on the topic of ocean carbon sequestration.

  12. BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo

    Directory of Open Access Journals (Sweden)

    Mihaela Crisan

    2016-03-01

    Full Text Available Hematopoietic stem cells (HSC, the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture: One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.

  13. Nondestructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): I. Relationships between concentrations of metals and arsenic in hair, spines, and soil.

    Science.gov (United States)

    D'Havé, Helga; Scheirs, Jan; Mubiana, Valentine Kayawe; Verhagen, Ron; Blust, Ronny; De Coen, Wim

    2005-09-01

    Conventional metal exposure assessment in terrestrial mammals is generally based on organ analyses of sacrificed animals. Few studies on mammals use nondestructive methodologies despite the growing ethical concern over the use of destructive sampling. Nondestructive methods involve minimal stress to populations and permit successive biomonitoring of the same populations and individuals. In the present study we assessed metal exposure of hedgehogs (Erinaceus europaeus) by investigating relationships between concentrations of metals (Ag, Al, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Zn) and As in soil samples and in hair and spines of hedgehogs. Samples were collected in seven study sites along a metal pollution gradient, characterized by decreasing total soil Ag, As, Cd, Cu, Ni, and Pb concentrations with increasing distance from a nonferrous metallurgic factory. For a number of elements, soil contamination was related both to distance to the smelter and to habitat. Soil concentrations were positively related to levels in hair and spines for Ag, As, Cd, and Pb and thus to hedgehog exposure. Metal concentrations in soil did not relate to metal concentrations in hair and spines for essential elements (e.g., Cu, Fe, Mn, Ni, and Zn), except Co in hair and soil. Our results demonstrate that, at least for nonessential elements, concentrations in soils can be used to predict contamination of these elements in hedgehogs or vice versa. Furthermore, hedgehog exposure increased toward the smelter and was higher for hedgehogs foraging in grasslands than for animals foraging in the forest. Moreover, we believe that hair and spines are promising tools in terrestrial wildlife exposure assessment studies of metals and As.

  14. The role of reforestation in carbon sequestration

    Science.gov (United States)

    Nave, L. E.; Walters, B. F.; Hofmeister, K.; Perry, C. H.; Mishra, U.; Domke, G. M.; Swanston, C.

    2017-12-01

    In the United States (U.S.), the maintenance of forest cover is a legal mandate for federally managed forest lands. Reforestation is one option for maintaining forest cover on managed or disturbed lands, and as a land use change can increase forest cover on previously non-forested lands, enhancing carbon (C)-based ecosystem services and functions such as the production of woody biomass for forest products and the mitigation of atmospheric CO2 pollution and climate change. Nonetheless, multiple assessments indicate that reforestation in the U.S. lags behind its potential, with continued ecosystem services and functions at risk if reforestation is not increased. In this context, there is need for multiple independent analyses that quantify the role of reforestation in C sequestration. Here, we report the findings of a large-scale data synthesis aimed at four objectives: 1) estimate C storage in major pools in forest and other land cover types; 2) quantify sources of variation in C pools; 3) compare the impacts of reforestation and afforestation on C pools; 4) assess whether results hold or diverge across ecoregions. Our data-driven analysis provides four key inferences regarding reforestation and other land use impacts on C sequestration. First, soils are the dominant C pool under all land cover types in the U.S., and spatial variation in soil C pool sizes has less to do with land cover than with other factors. Second, where historically cultivated lands are being reforested, topsoils are sequestering significant amounts of C, with the majority of reforested lands yet to reach sequestration capacity (relative to forested baseline). Third, the establishment of woody vegetation delivers immediate to multi-decadal C sequestration benefits in biomass and coarse woody debris pools, with two- to three-fold C sequestration benefits during the first several decades following planting. Fourth, opportunities to enhance C sequestration through reforestation vary among

  15. Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract

    NARCIS (Netherlands)

    van den Brink, G. R.; Hardwick, J. C. H.; Nielsen, C.; Xu, C.; ten Kate, F. J.; Glickman, J.; van Deventer, S. J. H.; Roberts, D. J.; Peppelenbosch, M. P.

    2003-01-01

    Background: Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the

  16. Status and potential of terrestrial carbon sequestration in West Virginia

    Science.gov (United States)

    Benktesh D. Sharma; Jingxin. Wang

    2011-01-01

    Terrestrial ecosystem management offers cost-effective ways to enhance carbon (C) sequestration. This study utilized C stock and C sequestration in forest and agricultural lands, abandoned mine lands, and harvested wood products to estimate the net current annual C sequestration in West Virginia. Several management options within these components were simulated using a...

  17. Targeting the Hedgehog pathway in cancer: can the spines be smoothened?

    Science.gov (United States)

    Ailles, Laurie; Siu, Lillian L

    2011-04-15

    Aberrant Hedgehog (Hh) pathway signaling has been suggested to play a role in the development of multiple solid tumors and hematologic malignancies. GDC-0449 is a novel first-in-human, first-in-class smoothened (SMO) inhibitor, which has completed its phase I evaluation and achieved proof of concept in tumors with Hh pathway mutations. ©2011 AACR.

  18. Intralobar pulmonary sequestration: a masquarader in tuberculosis prevalent population

    International Nuclear Information System (INIS)

    Ashraf, A.; Iqbal, M.

    2009-01-01

    Intra pulmonary sequestration is a rare congenital disorder that is characterized by malformation of pulmonary tissue having no connection to normal tracheobronchial tree and pulmonary arteries. This is a case history of 20 years old man initially misdiagnosed as Tuberculosis and later diagnosis of intra-lobar pulmonary sequestration was confirmed. There are few reports of this rare disorder globally and we are reporting the first case of Intrapulmonary Sequestration in Pakistan. (author)

  19. Exploration of public acceptance regarding CO2 underground sequestration technologies

    International Nuclear Information System (INIS)

    Uno, M.; Tokushige, K.; Mori, Y.; Furukawa, A.

    2005-01-01

    Mechanisms for gaining public acceptance of carbon dioxide (CO 2 ) aquifer sequestration were investigated through the use of questionnaires and focus group interviews. The study was performed as part of a CO 2 sequestration technology promotion project in Japan. The questionnaire portion of the study was conducted to determine public opinions and the extent of public awareness of CO 2 sequestration technologies. Questionnaires were distributed to undergraduate students majoring in environmental sociology. Participants were provided with newspaper articles related to CO 2 sequestration. The focus group study was conducted to obtain qualitative results to complement findings from the questionnaire survey. Results of the survey suggested that many participants were not particularly concerned about global warming, and had almost no knowledge about CO 2 sequestration. The opinions of some students were influenced by an awareness of similar types of facilities located near their homes. Attitudes were also influenced by the newspaper articles provided during the focus group sessions. However, many older participants did not trust information presented to them in newspaper format. Results suggested that many people identified afforestation as an alternative technology to CO 2 sequestration, and tended to think of CO 2 in negative terms as it contributed to global warming. Some participants assumed that CO 2 was harmful. The majority of respondents agreed with the development of CO 2 sequestration technologies as part of a program of alternative emissions abatement technologies. The provision of detailed information concerning CO 2 sequestration did not completely remove anxieties concerning the technology's potential negative impacts. It was concluded that a confident communications strategy is needed to persuade Japanese residents of the need to implement CO 2 sequestration technologies. 11 refs., 2 figs

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

    Science.gov (United States)

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

    2016-08-03

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

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

    Directory of Open Access Journals (Sweden)

    Sebastian Dworkin

    2016-08-01

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

  2. Hedgehogs on the move: Testing the effects of land use change on home range size and movement patterns of free-ranging Ethiopian hedgehogs.

    Science.gov (United States)

    Abu Baker, Mohammad A; Reeve, Nigel; Conkey, April A T; Macdonald, David W; Yamaguchi, Nobuyuki

    2017-01-01

    Degradation and alteration of natural environments because of agriculture and other land uses have major consequences on vertebrate populations, particularly on spatial organization and movement patterns. We used GPS tracking to study the effect of land use and sex on the home range size and movement of a typical model species, the Ethiopian hedgehogs. We used free-ranging hedgehogs from two areas with different land use practices: 24 from an area dominated by irrigated farms (12 ♂♂, 12 ♀♀) and 22 from a natural desert environment within a biosphere reserve (12 ♂♂, 10 ♀♀). Animals were significantly heavier in the resource-rich irrigated farms area (417.71 ±12.77SE g) in comparison to the natural desert area (376.37±12.71SE g). Both habitat and sex significantly influenced the home range size of hedgehogs. Home ranges were larger in the reserve than in the farms area. Total home ranges averaged 103 ha (±17 SE) for males and 42 ha (±11SE) for females in the farms area, but were much larger in the reserve averaging 230 ha (±33 SE) for males and 150 ha (±29 SE) for females. The home ranges of individuals of both sexes overlapped. Although females were heavier than males, body weight had no effect on home range size. The results suggest that resources provided in the farms (e.g. food, water, and shelters) influenced animal density and space use. Females aggregated around high-resource areas (either farms or rawdhats), whereas males roamed over greater distances, likely in search of mating opportunities to maximize reproductive success. Most individual home ranges overlapped with many other individuals of either sex, suggesting a non-territorial, promiscuous mating. Patterns of space use and habitat utilization are key factors in shaping aspects of reproductive biology and mating system. To minimize the impacts of agriculture on local wildlife, we recommend that biodiversity-friendly agro-environmental schemes be introduced in the Middle East where

  3. Hedgehogs on the move: Testing the effects of land use change on home range size and movement patterns of free-ranging Ethiopian hedgehogs.

    Directory of Open Access Journals (Sweden)

    Mohammad A Abu Baker

    Full Text Available Degradation and alteration of natural environments because of agriculture and other land uses have major consequences on vertebrate populations, particularly on spatial organization and movement patterns. We used GPS tracking to study the effect of land use and sex on the home range size and movement of a typical model species, the Ethiopian hedgehogs. We used free-ranging hedgehogs from two areas with different land use practices: 24 from an area dominated by irrigated farms (12 ♂♂, 12 ♀♀ and 22 from a natural desert environment within a biosphere reserve (12 ♂♂, 10 ♀♀. Animals were significantly heavier in the resource-rich irrigated farms area (417.71 ±12.77SE g in comparison to the natural desert area (376.37±12.71SE g. Both habitat and sex significantly influenced the home range size of hedgehogs. Home ranges were larger in the reserve than in the farms area. Total home ranges averaged 103 ha (±17 SE for males and 42 ha (±11SE for females in the farms area, but were much larger in the reserve averaging 230 ha (±33 SE for males and 150 ha (±29 SE for females. The home ranges of individuals of both sexes overlapped. Although females were heavier than males, body weight had no effect on home range size. The results suggest that resources provided in the farms (e.g. food, water, and shelters influenced animal density and space use. Females aggregated around high-resource areas (either farms or rawdhats, whereas males roamed over greater distances, likely in search of mating opportunities to maximize reproductive success. Most individual home ranges overlapped with many other individuals of either sex, suggesting a non-territorial, promiscuous mating. Patterns of space use and habitat utilization are key factors in shaping aspects of reproductive biology and mating system. To minimize the impacts of agriculture on local wildlife, we recommend that biodiversity-friendly agro-environmental schemes be introduced in the Middle

  4. State and Regional Control of Geological Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Reitze, Arnold [Univ. of Utah, Salt Lake City, UT (United States); Durrant, Marie [Univ. of Utah, Salt Lake City, UT (United States)

    2011-03-01

    The United States has economically recoverable coal reserves of about 261 billion tons, which is in excess of a 250-­year supply based on 2009 consumption rates. However, in the near future the use of coal may be legally restricted because of concerns over the effects of its combustion on atmospheric carbon dioxide concentrations. Carbon capture and geologic sequestration offer one method to reduce carbon emissions from coal and other hydrocarbon energy production. While the federal government is providing increased funding for carbon capture and sequestration, recent congressional legislative efforts to create a framework for regulating carbon emissions have failed. However, regional and state bodies have taken significant actions both to regulate carbon and facilitate its capture and sequestration. This article explores how regional bodies and state government are addressing the technical and legal problems that must be resolved in order to have a viable carbon sequestration program. Several regional bodies have formed regulations and model laws that affect carbon capture and storage, and three bodies comprising twenty-three states—the Regional Greenhouse Gas Initiative, the Midwest Regional Greenhouse Gas Reduction Accord, and the Western Climate initiative—have cap-­and-trade programs in various stages of development. State property, land use and environmental laws affect the development and implementation of carbon capture and sequestration projects, and unless federal standards are imposed, state laws on torts and renewable portfolio requirements will directly affect the liability and viability of these projects. This paper examines current state laws and legislative efforts addressing carbon capture and sequestration.

  5. Mast cells in the sheep, hedgehog and rat forebrain

    Science.gov (United States)

    MICHALOUDI, HELEN C.; PAPADOPOULOS, GEORGIOS C.

    1999-01-01

    The study was designed to reveal the distribution of various mast cell types in the forebrain of the adult sheep, hedgehog and rat. Based on their histochemical and immunocytochemical characteristics, mast cells were categorised as (1) connective tissue-type mast cells, staining metachromatically purple with the toluidine blue method, or pale red with the Alcian blue/safranin method, (2) mucosal-type or immature mast cells staining blue with the Alcian blue/safranin method and (3) serotonin immunopositive mast cells. All 3 types of brain mast cells in all species studied were located in both white and grey matter, often associated with intraparenchymal blood vessels. Their distribution pattern exhibited interspecies differences, while their number varied considerably not only between species but also between individuals of each species. A distributional left-right asymmetry, with more cells present on the left side, was observed in all species studied but it was most prominent in the sheep brain. In the sheep, mast cells were abundantly distributed in forebrain areas, while in the hedgehog and the rat forebrain, mast cells were less widely distributed and were relatively or substantially fewer in number respectively. A limited number of brain mast cells, in all 3 species, but primarily in the rat, were found to react both immunocytochemically to 5-HT antibody and histochemically with Alcian blue/safranin staining. PMID:10634696

  6. Parvalbumin and calbindin immunoreactivity in the cerebral cortex of the hedgehog (Erinaceus europaeus).

    Science.gov (United States)

    Ferrer, I; Zujar, M J; Admella, C; Alcantara, S

    1992-01-01

    To investigate the morphology and distribution of nonpyramidal neurons in the brain of insectivores, parvalbumin and calbindin 28 kDa immunoreactivity was examined in the cerebral cortex of the hedgehog (Erinaceus europaeus). Parvalbumin-immunoreactive cells were found in all layers of the isocortex, but in contrast to other mammals, a laminar organisation or specific regional distribution was not seen. Characteristic parvalbumin-immunoreactive neurons were multipolar cells with large ascending and descending dendrites extending throughout several layers. Calbindin-immunoreactive neurons were similar to those found in other species, although appearing in smaller numbers than in the cerebral cortex of more advanced mammals. The morphology and distribution of parvalbumin- and calbindin-immunoreactive cells in the piriform and entorhinal cortices were similar in hedgehogs and rodents. Parvalbumin-immunoreactive cells in the hippocampal complex were pyramidal-like and bitufted neurons, which were mainly found in the stratum oriens and stratum pyramidale of the hippocampus, and in the stratum moleculare and hilus of the fascia dentata. Heavily stained cells were found in the deep part of the stratum granulare. Intense calbindin immunoreactivity occurred mainly in the granule cell and molecular layers of the dentate gyrus and in the mossy fibre layer. The most outstanding feature in the hippocampal complex of the hedgehog was the extension of calbindin immunoreactivity to CA1 field of the hippocampus, suggesting, in agreement with other reports, that mossy fibres can establish synaptic contacts throughout the pyramidal cell layer. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:1452472

  7. Southeast Regional Carbon Sequestration Partnership

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth J. Nemeth

    2006-08-30

    The Southeast Regional Carbon Sequestration Partnership's (SECARB) Phase I program focused on promoting the development of a framework and infrastructure necessary for the validation and commercial deployment of carbon sequestration technologies. The SECARB program, and its subsequent phases, directly support the Global Climate Change Initiative's goal of reducing greenhouse gas intensity by 18 percent by the year 2012. Work during the project's two-year period was conducted within a ''Task Responsibility Matrix''. The SECARB team was successful in accomplishing its tasks to define the geographic boundaries of the region; characterize the region; identify and address issues for technology deployment; develop public involvement and education mechanisms; identify the most promising capture, sequestration, and transport options; and prepare action plans for implementation and technology validation activity. Milestones accomplished during Phase I of the project are listed below: (1) Completed preliminary identification of geographic boundaries for the study (FY04, Quarter 1); (2) Completed initial inventory of major sources and sinks for the region (FY04, Quarter 2); (3) Completed initial development of plans for GIS (FY04, Quarter 3); (4) Completed preliminary action plan and assessment for overcoming public perception issues (FY04, Quarter 4); (5) Assessed safety, regulatory and permitting issues (FY05, Quarter 1); (6) Finalized inventory of major sources/sinks and refined GIS algorithms (FY05, Quarter 2); (7) Refined public involvement and education mechanisms in support of technology development options (FY05, Quarter 3); and (8) Identified the most promising capture, sequestration and transport options and prepared action plans (FY05, Quarter 4).

  8. SOUTHWEST REGIONAL PARTNERSHIP ON CARBON SEQUESTRATION

    Energy Technology Data Exchange (ETDEWEB)

    Brian McPherson; Rick Allis; Barry Biediger; Joel Brown; Jim Cappa; George Guthrie; Richard Hughes; Eugene Kim; Robert Lee; Dennis Leppin; Charles Mankin; Orman Paananen; Rajesh Pawar; Tarla Peterson; Steve Rauzi; Jerry Stuth; Genevieve Young

    2004-11-01

    The Southwest Partnership Region includes six whole states, including Arizona, Colorado, Kansas, New Mexico, Oklahoma, and Utah, roughly one-third of Texas, and significant portions of adjacent states. The Partnership comprises a large, diverse group of expert organizations and individuals specializing in carbon sequestration science and engineering, as well as public policy and outreach. The main objective of the Southwest Partnership project is to achieve an 18% reduction in carbon intensity by 2012. The Partnership made great progress in this first year. Action plans for possible Phase II carbon sequestration pilot tests in the region are almost finished, including both technical and non-technical aspects necessary for developing and carrying out these pilot tests. All partners in the Partnership are taking an active role in evaluating and ranking optimum sites and technologies for capture and storage of CO{sub 2} in the Southwest Region. We are identifying potential gaps in all aspects of potential sequestration deployment issues.

  9. Physical and Biological Regulation of Carbon Sequestration in Tidal Marshes

    Science.gov (United States)

    Morris, J. T.; Callaway, J.

    2017-12-01

    The rate of carbon sequestration in tidal marshes is regulated by complex feedbacks among biological and physical factors including the rate of sea-level rise (SLR), biomass production, tidal amplitude, and the concentration of suspended sediment. We used the Marsh Equilibrium Model (MEM) to explore the effects on C-sequestration across a wide range of permutations of these variables. C-sequestration increased with the rate of SLR to a maximum, then down to a vanishing point at higher SLR when marshes convert to mudflats. An acceleration in SLR will increase C-sequestration in marshes that can keep pace, but at high rates of SLR this is only possible with high biomass and suspended sediment concentrations. We found that there were no feasible solutions at SLR >13 mm/yr for permutations of variables that characterize the great majority of tidal marshes, i.e., the equilibrium elevation exists below the lower vertical limit for survival of marsh vegetation. The rate of SLR resulting in maximum C-sequestration varies with biomass production. C-sequestration rates at SLR=1 mm/yr averaged only 36 g C m-2 yr-1, but at the highest maximum biomass tested (5000 g/m2) the mean C-sequestration reached 399 g C m-2 yr-1 at SLR = 14 mm/yr. The empirical estimate of C-sequestration in a core dated 50-years overestimates the theoretical long-term rate by 34% for realistic values of decomposition rate and belowground production. The overestimate of the empirical method arises from the live and decaying biomass contained within the carbon inventory above the marker horizon, and overestimates were even greater for shorter surface cores.

  10. Hedgehog-PKA signaling and gnrh3 regulate the development of zebrafish gnrh3 neurons.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Kuo

    Full Text Available GnRH neurons secrete GnRH that controls the development of the reproduction system. Despite many studies, the signals controlling the development of GnRH neurons from its progenitors have not been fully established. To understand the development of GnRH neurons, we examined the development of gnrh3-expressing cells using a transgenic zebrafish line that expresses green fluorescent protein (GFP and LacZ driven by the gnrh3 promoter. GFP and LacZ expression recapitulated that of gnrh3 in the olfactory region, olfactory bulb and telencephalon. Depletion of gnrh3 by morpholinos led to a reduction of GFP- and gnrh3-expressing cells, while over-expression of gnrh3 mRNA increased the number of these cells. This result indicates a positive feed-forward regulation of gnrh3 cells by gnrh3. The gnrh3 cells were absent in embryos that lack Hedgehog signaling, but their numbers were increased in embryos overexpressing shhb. We manipulated the amounts of kinase that antagonizes the Hedgehog signaling pathway, protein kinase A (PKA, by treating embryos with PKA activator forskolin or by injecting mRNAs encoding its constitutively active catalytic subunit (PKA* and dominant negative regulatory subunit (PKI into zebrafish embryos. PKA* misexpression or forskolin treatment decreased GFP cell numbers, while PKI misexpression led to ectopic production of GFP cells. Our data indicate that the Hedgehog-PKA pathway participates in the development of gnrh3-expressing neurons during embryogenesis.

  11. Downregulation of the Sonic Hedgehog/Gli pathway transcriptional target Neogenin-1 is associated with basal cell carcinoma aggressiveness.

    Science.gov (United States)

    Casas, Bárbara S; Adolphe, Christelle; Lois, Pablo; Navarrete, Nelson; Solís, Natalia; Bustamante, Eva; Gac, Patricio; Cabané, Patricio; Gallegos, Ivan; Wainwright, Brandon J; Palma, Verónica

    2017-10-13

    Basal Cell Carcinoma (BCC) is one of the most diagnosed cancers worldwide. It develops due to an unrestrained Sonic Hedgehog (SHH) signaling activity in basal cells of the skin. Certain subtypes of BCC are more aggressive than others, although the molecular basis of this phenomenon remains unknown. We have previously reported that Neogenin-1 (NEO1) is a downstream target gene of the SHH/GLI pathway in neural tissue. Given that SHH participates in epidermal homeostasis, here we analyzed the epidermal expression of NEO1 in order to identify whether it plays a role in adult epidermis or BCC. We describe the mRNA and protein expression profile of NEO1 and its ligands (Netrin-1 and RGMA) in human and mouse control epidermis and in a broad range of human BCCs. We identify in human BCC a significant positive correlation in the levels of NEO1 receptor, NTN-1 and RGMA ligands with respect to GLI1 , the main target gene of the canonical SHH pathway. Moreover, we show via cyclopamine inhibition of the SHH/GLI pathway of ex vivo cultures that NEO1 likely functions as a downstream target of SHH/GLI signaling in the skin. We also show how Neo1 expression decreases throughout BCC progression in the K14-Cre:Ptch1 lox/lox mouse model and that aggressive subtypes of human BCC exhibit lower levels of NEO1 than non-aggressive BCC samples. Taken together, these data suggest that NEO1 is a SHH/GLI target in epidermis. We propose that NEO1 may be important in tumor onset and is then down-regulated in advanced BCC or aggressive subtypes.

  12. Integrated QSAR study for inhibitors of Hedgehog Signal Pathway against multiple cell lines:a collaborative filtering method.

    Science.gov (United States)

    Gao, Jun; Che, Dongsheng; Zheng, Vincent W; Zhu, Ruixin; Liu, Qi

    2012-07-31

    The Hedgehog Signaling Pathway is one of signaling pathways that are very important to embryonic development. The participation of inhibitors in the Hedgehog Signal Pathway can control cell growth and death, and searching novel inhibitors to the functioning of the pathway are in a great demand. As the matter of fact, effective inhibitors could provide efficient therapies for a wide range of malignancies, and targeting such pathway in cells represents a promising new paradigm for cell growth and death control. Current research mainly focuses on the syntheses of the inhibitors of cyclopamine derivatives, which bind specifically to the Smo protein, and can be used for cancer therapy. While quantitatively structure-activity relationship (QSAR) studies have been performed for these compounds among different cell lines, none of them have achieved acceptable results in the prediction of activity values of new compounds. In this study, we proposed a novel collaborative QSAR model for inhibitors of the Hedgehog Signaling Pathway by integration the information from multiple cell lines. Such a model is expected to substantially improve the QSAR ability from single cell lines, and provide useful clues in developing clinically effective inhibitors and modifications of parent lead compounds for target on the Hedgehog Signaling Pathway. In this study, we have presented: (1) a collaborative QSAR model, which is used to integrate information among multiple cell lines to boost the QSAR results, rather than only a single cell line QSAR modeling. Our experiments have shown that the performance of our model is significantly better than single cell line QSAR methods; and (2) an efficient feature selection strategy under such collaborative environment, which can derive the commonly important features related to the entire given cell lines, while simultaneously showing their specific contributions to a specific cell-line. Based on feature selection results, we have proposed several

  13. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  14. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  15. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer

  16. Catecholaminergic and serotoninergic fibres innervate the ventricular system of the hedgehog CNS.

    Science.gov (United States)

    Michaloudi, H C; Papadopoulos, G C

    1996-01-01

    Immunocytochemistry with antisera against serotonin (5-HT), dopamine (DA) and noradrenaline (NA) was used to detect monoaminergic (MA) fibres in the ventricular system of the hedgehog Erinaceus europaeus. Light microscopic examination of immunocytochemically stained sections revealed that the ventricular system of the hedgehog is unique among mammals in that the choroid plexuses receive CA axons and that the supraependyma and subependyma of the cerebral ventricles and the spinal central canal are innervated both by serotoninergic and catecholaminergic (CA) fibres. Supraependymal 5-HT axons were generally more abundant and created at places a large number of interconnected basket-like structures, whereas CA fibres were usually directed towards the ventricular lumen. In the lateral ventricles, CA fibres were more numerous in the ependyma lining grey matter, whereas a higher 5-HT innervation density was observed in the area between the corpus callosum and the caudate nucleus or the septum. In the 3rd ventricle, the ependyma of its dorsal part exhibited a higher 5-HT and NA innervation density, whereas DA fibres were preferentially distributed in the ventral half of the basal region. The ependyma lining the cerebral aqueduct displayed a higher MA innervation density in its ventral part. The ependymal wall of the 4th ventricle exhibited an extremely dense 5-HT innervation, mainly in the floor of the ventricle, relatively fewer NA fibres and only sparse DA ones. Few NA and relatively more 5-HT fibres were detected in the ependyma of the central canal. Finally, the circumventricular organs were unevenly innervated by the 3 types of MA fibres. The extensive monoaminergic innervation of the hedgehog ventricular system described here probably reflects a transitory evolutionary stage in the phylogeny of the MA systems with presently unknown functional implications. Images Fig. 1 Fig. 2 Figs 3-8 Figs 9-14 Figs 15-20 PMID:8886949

  17. NHR-23 dependent collagen and hedgehog-related genes required for molting

    International Nuclear Information System (INIS)

    Kouns, Nathaniel A.; Nakielna, Johana; Behensky, Frantisek; Krause, Michael W.; Kostrouch, Zdenek; Kostrouchova, Marta

    2011-01-01

    Highlights: → NHR-23 is a critical regulator of nematode development and molting. → The manuscript characterizes the loss-of-function phenotype of an nhr-23 mutant. → Whole genome expression analysis identifies new potential targets of NHR-23. → Hedgehog-related genes are identified as NHR-23 dependent genes. → New link between sterol mediated signaling and regulation by NHR-23 is found. -- Abstract: NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in Caenorhabditis elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.

  18. Multicentric epitheliotropic T-cell lymphoma in an African hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Chung, Tae-Ho; Kim, Hyo-Jin; Choi, Ul-Soo

    2014-12-01

    A 2-year-old female African hedgehog was presented with a 5-month history of pruritus, and diffuse spine and hair loss. A dermatologic examination revealed erythema, excoriation, scales, and crusting affecting the face, flanks, forelimbs, hindlimbs, and dorsal and ventral abdomen. Fine-needle aspiration was performed and skin biopsies were taken from several lesions for cytologic and histologic evaluation. The aspirates yielded smears characterized by a monomorphic population of medium-sized to large lymphocytes with scant to moderate amounts of clear to moderately basophilic cytoplasm and distinct nucleoli along with a low number of cytoplasmic fragments. On histopathologic examination, there were dense dermal lymphoid infiltrates invading the dermis and a monomorphic population of round cells that had infiltrated the overlying epidermis. Epitheliotropic cutaneous lymphoma was diagnosed based on morphologic features. Additional immunochemical analysis using anti-CD3 and anti-CD79a antibodies revealed strong CD3 expression by the tumor cells, which confirmed epitheliotropic cutaneous T-cell lymphoma. This is the first description of a multicentric pattern of epitheliotropic cutaneous T-cell lymphoma in an African hedgehog. © 2014 American Society for Veterinary Clinical Pathology.

  19. NHR-23 dependent collagen and hedgehog-related genes required for molting

    Energy Technology Data Exchange (ETDEWEB)

    Kouns, Nathaniel A.; Nakielna, Johana; Behensky, Frantisek [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic); Krause, Michael W. [Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD (United States); Kostrouch, Zdenek [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic); Kostrouchova, Marta, E-mail: marta.kostrouchova@lf1.cuni.cz [Laboratory of Model Systems, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague (Czech Republic)

    2011-10-07

    Highlights: {yields} NHR-23 is a critical regulator of nematode development and molting. {yields} The manuscript characterizes the loss-of-function phenotype of an nhr-23 mutant. {yields} Whole genome expression analysis identifies new potential targets of NHR-23. {yields} Hedgehog-related genes are identified as NHR-23 dependent genes. {yields} New link between sterol mediated signaling and regulation by NHR-23 is found. -- Abstract: NHR-23, a conserved member of the nuclear receptor family of transcription factors, is required for normal development in Caenorhabditis elegans where it plays a critical role in growth and molting. In a search for NHR-23 dependent genes, we performed whole genome comparative expression microarrays on both control and nhr-23 inhibited synchronized larvae. Genes that decreased in response to nhr-23 RNAi included several collagen genes. Unexpectedly, several hedgehog-related genes were also down-regulated after nhr-23 RNAi. A homozygous nhr-23 deletion allele was used to confirm the RNAi knockdown phenotypes and the changes in gene expression. Our results indicate that NHR-23 is a critical co-regulator of functionally linked genes involved in growth and molting and reveal evolutionary parallels among the ecdysozoa.

  20. Five-dimensional Monopole Equation with Hedge-Hog Ansatz and Abel's Differential Equation

    OpenAIRE

    Kihara, Hironobu

    2008-01-01

    We review the generalized monopole in the five-dimensional Euclidean space. A numerical solution with the Hedge-Hog ansatz is studied. The Bogomol'nyi equation becomes a second order autonomous non-linear differential equation. The equation can be translated into the Abel's differential equation of the second kind and is an algebraic differential equation.

  1. Export from Seagrass Meadows Contributes to Marine Carbon Sequestration

    KAUST Repository

    Duarte, Carlos M.; Krause-Jensen, Dorte

    2017-01-01

    Seagrasses export a substantial portion of their primary production, both in particulate and dissolved organic form, but the fate of this export production remains unaccounted for in terms of seagrass carbon sequestration. Here we review available evidence on the fate of seagrass carbon export to conclude that this represents a significant contribution to carbon sequestration, both in sediments outside seagrass meadows and in the deep sea. The evidence presented implies that the contribution of seagrass meadows to carbon sequestration has been underestimated by only including carbon burial within seagrass sediments.

  2. Export from Seagrass Meadows Contributes to Marine Carbon Sequestration

    KAUST Repository

    Duarte, Carlos M.

    2017-01-17

    Seagrasses export a substantial portion of their primary production, both in particulate and dissolved organic form, but the fate of this export production remains unaccounted for in terms of seagrass carbon sequestration. Here we review available evidence on the fate of seagrass carbon export to conclude that this represents a significant contribution to carbon sequestration, both in sediments outside seagrass meadows and in the deep sea. The evidence presented implies that the contribution of seagrass meadows to carbon sequestration has been underestimated by only including carbon burial within seagrass sediments.

  3. International Collaboration on CO2 Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Peter H. Israelsson; E. Eric Adams

    2007-06-30

    On December 4, 1997, the US Department of Energy (USDOE), the New Energy and Industrial Technology Development Organization of Japan (NEDO), and the Norwegian Research Council (NRC) entered into a Project Agreement for International Collaboration on CO{sub 2} Ocean Sequestration. Government organizations from Japan, Canada, and Australia, and a Swiss/Swedish engineering firm later joined the agreement, which outlined a research strategy for ocean carbon sequestration via direct injection. The members agreed to an initial field experiment, with the hope that if the initial experiment was successful, there would be subsequent field evaluations of increasingly larger scale to evaluate environmental impacts of sequestration and the potential for commercialization. The evolution of the collaborative effort, the supporting research, and results for the International Collaboration on CO{sub 2} Ocean Sequestration were documented in almost 100 papers and reports, including 18 peer-reviewed journal articles, 46 papers, 28 reports, and 4 graduate theses. These efforts were summarized in our project report issued January 2005 and covering the period August 23, 1998-October 23, 2004. An accompanying CD contained electronic copies of all the papers and reports. This report focuses on results of a two-year sub-task to update an environmental assessment of acute marine impacts resulting from direct ocean sequestration. The approach is based on the work of Auerbach et al. [6] and Caulfield et al. [20] to assess mortality to zooplankton, but uses updated information concerning bioassays, an updated modeling approach and three modified injection scenarios: a point release of negatively buoyant solid CO{sub 2} hydrate particles from a moving ship; a long, bottom-mounted diffuser discharging buoyant liquid CO{sub 2} droplets; and a stationary point release of hydrate particles forming a sinking plume. Results suggest that in particular the first two discharge modes could be

  4. Intralobar bronchopulmonary sequestration with large aberrant vessel presenting as recurrent pneumonias

    International Nuclear Information System (INIS)

    Noomani, A.Z.; Toori, K.U.

    2014-01-01

    Bronchopulmonary sequestration is a rare congenital malformation of the lower respiratory tract comprising of a nonfunctioning lung tissue mass that lacks normal communication with the tracheobronchial tree. The diagnosis may be easily missed as many of the symptoms of bronchopulmonary sequestration overlap with that of other pulmonary diseases. Bronchopulmonary sequestration can be complicated by recurrent infections, hemorrhage and malignant transformation and, therefore, needs to be timely diagnosed and resected to decrease both morbidity and mortality. A high degree of suspicion in the differential diagnosis helps diagnose the positive cases. The parenchymal abnormalities associated with bronchopulmonary sequestration are best visualized using computed tomography, although their appearance is variable. We report the case of a 14 years old boy with intralobar bronchopulmonary sequestration with the sole manifestation of recurrent pneumonias. (author)

  5. Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1

    NARCIS (Netherlands)

    Lodder, E. M.; Hoogeboom, A. J. M.; Coert, J. H.; de Graaff, E.

    2008-01-01

    Brachydactyly type A1 is a limb malformation characterized by a uniform shortening of the middle phalanges in all digits. Mutations in the Indian hedgehog (IHH) gene were shown to be the cause of this autosomal dominant disorder. The IHH protein is known to be an important signaling molecule

  6. Signaling domain of Sonic Hedgehog as cannibalistic calcium-regulated zinc-peptidase.

    Directory of Open Access Journals (Sweden)

    Rocio Rebollido-Rios

    2014-07-01

    Full Text Available Sonic Hedgehog (Shh is a representative of the evolutionary closely related class of Hedgehog proteins that have essential signaling functions in animal development. The N-terminal domain (ShhN is also assigned to the group of LAS proteins (LAS = Lysostaphin type enzymes, D-Ala-D-Ala metalloproteases, Sonic Hedgehog, of which all members harbor a structurally well-defined Zn2+ center; however, it is remarkable that ShhN so far is the only LAS member without proven peptidase activity. Another unique feature of ShhN in the LAS group is a double-Ca2+ center close to the zinc. We have studied the effect of these calcium ions on ShhN structure, dynamics, and interactions. We find that the presence of calcium has a marked impact on ShhN properties, with the two calcium ions having different effects. The more strongly bound calcium ion significantly stabilizes the overall structure. Surprisingly, the binding of the second calcium ion switches the putative catalytic center from a state similar to LAS enzymes to a state that probably is catalytically inactive. We describe in detail the mechanics of the switch, including the effect on substrate co-ordinating residues and on the putative catalytic water molecule. The properties of the putative substrate binding site suggest that ShhN could degrade other ShhN molecules, e.g. by cleavage at highly conserved glycines in ShhN. To test experimentally the stability of ShhN against autodegradation, we compare two ShhN mutants in vitro: (1 a ShhN mutant unable to bind calcium but with putative catalytic center intact, and thus, according to our hypothesis, a constitutively active peptidase, and (2 a mutant carrying additionally mutation E177A, i.e., with the putative catalytically active residue knocked out. The in vitro results are consistent with ShhN being a cannibalistic zinc-peptidase. These experiments also reveal that the peptidase activity depends on pH.

  7. Human germline hedgehog pathway mutations predispose to fatty liver.

    Science.gov (United States)

    Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

    2017-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

  8. Vegetation carbon sequestration in Chinese forests from 2010 to 2050.

    Science.gov (United States)

    He, Nianpeng; Wen, Ding; Zhu, Jianxing; Tang, Xuli; Xu, Li; Zhang, Li; Hu, Huifeng; Huang, Mei; Yu, Guirui

    2017-04-01

    Forests store a large part of the terrestrial vegetation carbon (C) and have high C sequestration potential. Here, we developed a new forest C sequestration (FCS) model based on the secondary succession theory, to estimate vegetation C sequestration capacity in China's forest vegetation. The model used the field measurement data of 3161 forest plots and three future climate scenarios. The results showed that logistic equations provided a good fit for vegetation biomass with forest age in natural and planted forests. The FCS model has been verified with forest biomass data, and model uncertainty is discussed. The increment of vegetation C storage in China's forest vegetation from 2010 to 2050 was estimated as 13.92 Pg C, while the average vegetation C sequestration rate was 0.34 Pg C yr -1 with a 95% confidence interval of 0.28-0.42 Pg C yr -1 , which differed significantly between forest types. The largest contributor to the increment was deciduous broadleaf forest (37.8%), while the smallest was deciduous needleleaf forest (2.7%). The vegetation C sequestration rate might reach its maximum around 2020, although vegetation C storage increases continually. It is estimated that vegetation C sequestration might offset 6-8% of China's future emissions. Furthermore, there was a significant negative relationship between vegetation C sequestration rate and C emission rate in different provinces of China, suggesting that developed provinces might need to compensate for undeveloped provinces through C trade. Our findings will provide valuable guidelines to policymakers for designing afforestation strategies and forest C trade in China. © 2016 John Wiley & Sons Ltd.

  9. Life on the edge : hedgehog traffic victims and mitigation strategies in an anthropogenic landscape

    NARCIS (Netherlands)

    Huijser, M.P.

    2000-01-01

    This study focused on the most frequently recorded mammal species in road-kill surveys in western Europe: the hedgehog (Erinaceus europaeus). Investigations were conducted in an anthropogenic landscape and had two major aims:

    1. to quantify the effects of traffic

    2. Morphology, histochemistry and glycosylation of the placenta and associated tissues in the European hedgehog (Erinaceus europaeus)

      DEFF Research Database (Denmark)

      Jones, Carolyn J P; Carter, A M; Allen, W R

      2016-01-01

      glycosylated. Yolk sac inner and outer endoderm expressed similar glycans except for N-acetylgalactosamine residues in endodermal acini. DISCUSSION: New features of near-term hedgehog placenta and associated tissues are presented, including their glycosylation, and novel yolk sac acinar structures......INTRODUCTION: There are few descriptions of the placenta and associated tissues of the European hedgehog (Erinaceus europaeus) and here we present findings on a near-term pregnant specimen. METHODS: Tissues were examined grossly and then formalin fixed and wax-embedded for histology...... and immunocytochemistry (cytokeratin) and resin embedded for lectin histochemistry. RESULTS: Each of four well-developed and near term hoglets displayed a discoid, haemochorial placenta with typical labyrinth and spongy zones. In addition there was a paraplacenta incorporating Reichert's membrane and a largely detached...

    3. Biologically Enhanced Carbon Sequestration: Research Needs and Opportunities

      Energy Technology Data Exchange (ETDEWEB)

      Oldenburg, Curtis; Oldenburg, Curtis M.; Torn, Margaret S.

      2008-03-21

      Fossil fuel combustion, deforestation, and biomass burning are the dominant contributors to increasing atmospheric carbon dioxide (CO{sub 2}) concentrations and global warming. Many approaches to mitigating CO{sub 2} emissions are being pursued, and among the most promising are terrestrial and geologic carbon sequestration. Recent advances in ecology and microbial biology offer promising new possibilities for enhancing terrestrial and geologic carbon sequestration. A workshop was held October 29, 2007, at Lawrence Berkeley National Laboratory (LBNL) on Biologically Enhanced Carbon Sequestration (BECS). The workshop participants (approximately 30 scientists from California, Illinois, Oregon, Montana, and New Mexico) developed a prioritized list of research needed to make progress in the development of biological enhancements to improve terrestrial and geologic carbon sequestration. The workshop participants also identified a number of areas of supporting science that are critical to making progress in the fundamental research areas. The purpose of this position paper is to summarize and elaborate upon the findings of the workshop. The paper considers terrestrial and geologic carbon sequestration separately. First, we present a summary in outline form of the research roadmaps for terrestrial and geologic BECS. This outline is elaborated upon in the narrative sections that follow. The narrative sections start with the focused research priorities in each area followed by critical supporting science for biological enhancements as prioritized during the workshop. Finally, Table 1 summarizes the potential significance or 'materiality' of advances in these areas for reducing net greenhouse gas emissions.

    4. Black carbon sequestration as an alternative to bioenergy

      International Nuclear Information System (INIS)

      Fowles, Malcolm

      2007-01-01

      Most policy and much research concerning the application of biomass to reduce global warming gas emissions has concentrated either on increasing the Earth's reservoir of biomass or on substituting biomass for fossil fuels, with or without CO 2 sequestration. Suggested approaches entail varied risks of impermanence, delay, high costs, and unknowable side-effects. An under-researched alternative approach is to extract from biomass black (elemental) carbon, which can be permanently sequestered as mineral geomass and may be relatively advantageous in terms of those risks. This paper reviews salient features of black carbon sequestration and uses a high-level quantitative model to compare the approach with the alternative use of biomass to displace fossil fuels. Black carbon has been demonstrated to produce significant benefits when sequestered in agricultural soil, apparently without bad side-effects. Black carbon sequestration appears to be more efficient in general than energy generation, in terms of atmospheric carbon saved per unit of biomass; an exception is where biomass can efficiently displace coal-fired generation. Black carbon sequestration can reasonably be expected to be relatively quick and cheap to apply due to its short value chain and known technology. However, the model is sensitive to several input variables, whose values depend heavily on local conditions. Because characteristics of black carbon sequestration are only known from limited geographical contexts, its worldwide potential will not be known without multiple streams of research, replicated in other contexts. (author)

    5. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs.

      Science.gov (United States)

      Choi, Kyung-Suk; Harfe, Brian D

      2011-06-07

      The vertebrae notochord is a transient rod-like structure that produces secreted factors that are responsible for patterning surrounding tissues. During later mouse embryogenesis, the notochord gives rise to the middle part of the intervertebral disc, called the nucleus pulposus. Currently, very little is known about the molecular mechanisms responsible for forming the intervertebral discs. Here we demonstrate that hedgehog signaling is required for formation of the intervertebral discs. Removal of hedgehog signaling in the notochord and nearby floorplate resulted in the formation of an aberrant notochord sheath that normally surrounds this structure. In the absence of the notochord sheath, small nuclei pulposi were formed, with most notochord cells dispersed throughout the vertebral bodies during embryogenesis. Our data suggest that the formation of the notochord sheath requires hedgehog signaling and that the sheath is essential for maintaining the rod-like structure of the notochord during early embryonic development. As notochord cells form nuclei pulposi, we propose that the notochord sheath functions as a "wrapper" around the notochord to constrain these cells along the vertebral column.

    6. Consequences of co-benefits for the efficient design of carbon sequestration programs

      International Nuclear Information System (INIS)

      Feng, H.; Kling, C.L.

      2005-01-01

      The social efficiency of private carbon markets that also included trading in agricultural soil carbon sequestration with significant associated co-benefits were considered. Three topics related to the presence of co-benefits that sequester carbon were examined: (1) the consequences of co-benefits from carbon sinks and carbon abatement technology on the efficiency of carbon markets; (2) the efficient supply of carbon sequestration and co-benefits when there is spatial heterogeneity; and (3) the consequences of the presence of a carbon market when there is also a government supported conservation program. Co-benefits from carbon sinks and abatement were considered in relation to the socially efficient level of sequestration. The supply of carbon sequestration and co-benefits were then considered when fields differed in their potential to provide carbon and other environmental benefits. An empirical example of the economic characteristics of carbon sequestration and co-benefits in the Upper Mississippi River Basin was presented, in which the sequestration practice of land retirement with planting of perennial grasses was examined. Two sets of figures were used to illustrate the relationship between the cost of carbon sequestration and its marginal co-benefits: the marginal cost and the marginal co-benefits of carbon sequestration in a carbon market; and the marginal cost of carbon sequestration under a policy designed to maximize a bundle of environmental benefits. It was demonstrated that the relationship between carbon and its associated co-benefits will affect the efficiency of policy instruments designed for carbon sequestration. It was recommended that policy-makers consider that there are already a multitude of existing conservation programmes that result in significant carbon sequestration in many countries, and that nascent carbon markets are emerging in countries that have not ratified the Kyoto Protocol. The efficient level and location of carbon

    7. Research advances in Hedgehog signaling pathway in hepatocellular carcinoma

      Directory of Open Access Journals (Sweden)

      LIU Jia

      2015-02-01

      Full Text Available Hedgehog (Hh signaling pathway is present in many animals and plays an important role in regulating embryonic development and differentiation. Aberrant activation of Hh signaling contributes to the pathogenesis of many malignancies. Recent studies have shown that dysregulated Hh signaling pathway participates in the tumorigenesis, tumor invasion, and metastasis of hepatocellular carcinoma (HCC. Investigation of the relationship between Hh signaling pathway and HCC will help elucidate the molecular mechanism of pathogenesis of HCC and provide a new insight into the development of novel anticancer therapy and therapeutic target.

    8. Radiological diagnosis of pulmonary sequestration: review of six cases, including one bilateral

      International Nuclear Information System (INIS)

      Brito Pacheco, E.M. de; Cazerta, N.M.G.; Marins, J.L.C.; Prando, A.

      1989-01-01

      Radiological diagnosis of pulmonary sequestration: review of six cases, including one bilateral. Pulmonary sequestration is an uncommon disorder consisting of aberrant pulmonary tissue that has no normal connection with the bronchial tree or with the pulmonary arteries, but is supplied by a systemic artery which usually arises from the aorta. Six cases of pulmonary sequestration are presented and the radiological manifestation of this rare congenital disorder are discussed. These sequestrations were intralobar/unilateral in four patients, extralobar/unilateral in one and extralobar/bilateral in the other patient. Special attention is given to the extremely uncommon bilateral sequestration. To our knowledge only four cases of this form of disease has been described in the literature. (author) [pt

    9. Live imaging of individual cell divisions in mouse neuroepithelium shows asymmetry in cilium formation and Sonic hedgehog response

      Directory of Open Access Journals (Sweden)

      Piotrowska-Nitsche Karolina

      2012-05-01

      Full Text Available Abstract Background Primary cilia are microtubule-based sensory organelles that play important roles in developmental signaling pathways. Recent work demonstrated that, in cell culture, the daughter cell that inherits the older mother centriole generates a primary cilium and responds to external stimuli prior to its sister cell. This asynchrony in timing of cilia formation could be especially critical during development as cell divisions are required for both differentiation and maintenance of progenitor cell niches. Methods Here we integrate several fluorescent markers and use ex vivo live imaging of a single cell division within the mouse E8.5 neuroepithelium to reveal both the formation of a primary cilium and the transcriptional response to Sonic hedgehog in the daughter cells. Results We show that, upon cell division, cilia formation and the Sonic hedgehog response are asynchronous between the daughter cells. Conclusions Our results demonstrate that we can directly observe single cell divisions within the developing neuroepithelium and concomitantly monitor cilium formation or Sonic hedgehog response. We expect this method to be especially powerful in examining whether cellular behavior can lead to both differentiation and maintenance of cells in a progenitor niche.

    10. Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.

      Science.gov (United States)

      Mao, Suifang; Shah, Alok S; Moninger, Thomas O; Ostedgaard, Lynda S; Lu, Lin; Tang, Xiao Xiao; Thornell, Ian M; Reznikov, Leah R; Ernst, Sarah E; Karp, Philip H; Tan, Ping; Keshavjee, Shaf; Abou Alaiwa, Mahmoud H; Welsh, Michael J

      2018-02-06

      Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gα i and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. Copyright © 2018 the Author(s). Published by PNAS.

    11. Southeast Regional Carbon Sequestration Partnership (SECARB)

      Energy Technology Data Exchange (ETDEWEB)

      Kenneth J. Nemeth

      2005-09-30

      The Southeast Regional Carbon Sequestration Partnership (SECARB) is a diverse partnership covering eleven states involving the Southern States Energy Board (SSEB) an interstate compact; regulatory agencies and/or geological surveys from member states; the Electric Power Research Institute (EPRI); academic institutions; a Native American enterprise; and multiple entities from the private sector. Figure 1 shows the team structure for the partnership. In addition to the Technical Team, the Technology Coalition, an alliance of auxiliary participants, in the project lends yet more strength and support to the project. The Technology Coalition, with its diverse representation of various sectors, is integral to the technical information transfer, outreach, and public perception activities of the partnership. The Technology Coalition members, shown in Figure 2, also provide a breadth of knowledge and capabilities in the multiplicity of technologies needed to assure a successful outcome to the project and serve as an extremely important asset to the partnership. The eleven states comprising the multi-state region are: Alabama; Arkansas; Florida; Georgia; Louisiana; Mississippi; North Carolina; South Carolina; Tennessee; Texas; and Virginia. The states making up the SECARB area are illustrated in Figure 3. The primary objectives of the SECARB project include: (1) Supporting the U.S. Department of Energy (DOE) Carbon Sequestration Program by promoting the development of a framework and infrastructure necessary for the validation and deployment of carbon sequestration technologies. This requires the development of relevant data to reduce the uncertainties and risks that are barriers to sequestration, especially for geologic storage in the SECARB region. Information and knowledge are the keys to establishing a regional carbon dioxide (CO{sub 2}) storage industry with public acceptance. (2) Supporting the President's Global Climate Change Initiative with the goal of reducing

    12. BIG SKY CARBON SEQUESTRATION PARTNERSHIP

      Energy Technology Data Exchange (ETDEWEB)

      Susan M. Capalbo

      2004-10-31

      The Big Sky Carbon Sequestration Partnership, led by Montana State University, is comprised of research institutions, public entities and private sectors organizations, and the Confederated Salish and Kootenai Tribes and the Nez Perce Tribe. Efforts under this Partnership fall into four areas: evaluation of sources and carbon sequestration sinks; development of GIS-based reporting framework; designing an integrated suite of monitoring, measuring, and verification technologies; and initiating a comprehensive education and outreach program. At the first two Partnership meetings the groundwork was put in place to provide an assessment of capture and storage capabilities for CO{sub 2} utilizing the resources found in the Partnership region (both geological and terrestrial sinks), that would complement the ongoing DOE research. During the third quarter, planning efforts are underway for the next Partnership meeting which will showcase the architecture of the GIS framework and initial results for sources and sinks, discuss the methods and analysis underway for assessing geological and terrestrial sequestration potentials. The meeting will conclude with an ASME workshop. The region has a diverse array of geological formations that could provide storage options for carbon in one or more of its three states. Likewise, initial estimates of terrestrial sinks indicate a vast potential for increasing and maintaining soil C on forested, agricultural, and reclaimed lands. Both options include the potential for offsetting economic benefits to industry and society. Steps have been taken to assure that the GIS-based framework is consistent among types of sinks within the Big Sky Partnership area and with the efforts of other western DOE partnerships. Efforts are also being made to find funding to include Wyoming in the coverage areas for both geological and terrestrial sinks and sources. The Partnership recognizes the critical importance of measurement, monitoring, and verification

  1. Indian Hedgehog Controls Proliferation and Differentiation in Skin Tumorigenesis and Protects against Malignant Progression

    Directory of Open Access Journals (Sweden)

    Parisa Kakanj

    2013-07-01

    Full Text Available Mutations in the hedgehog pathway drive the formation of tumors in many different organs, including the development of basal cell carcinoma in the skin. However, little is known about the role of epidermal Indian hedgehog (Ihh in skin physiology. Using mouse genetics, we identified overlapping and distinct functions of Ihh in different models of epidermal tumorigenesis. Epidermal deletion of Ihh resulted in increased formation of benign squamous papilloma. Strikingly, Ihh-deficient mice showed an increase in malignant squamous cell carcinoma and developed lung and lymph node metastases. In a sebaceous gland tumor model, Ihh deficiency inhibited tumor cell differentiation. More mechanistically, IHH stimulated cell proliferation by activating the transcription factor GLI2 in human keratinocytes and human tumors. Thus, our results uncover important functions for Ihh signaling in controlling proliferation, differentiation, malignant progression, and metastasis of epithelial cancer, establishing Ihh as a gatekeeper for controlling the grade of tumor malignancy.

  2. Treatment of Pulmonary Sequestrations by Means of Endovascular Embolization: Future or Fashion?

    Directory of Open Access Journals (Sweden)

    Jeroen Diks

    2011-01-01

    Full Text Available Bronchopulmonary sequestration is a rare malformation of the lower respiratory tract. Several methods of treatment have been described since the first publication. We present two cases of female adult patients with bronchopulmonary sequestration. In the first patient an unsuccessful attempt to treat the bronchopulmonary sequestration by means of arterial embolization is described. She was subsequently treated by means of surgical resection, which was the primary treatment for the second patient. Although endovascular techniques are becoming promising, in our opinion surgical resection remains the unique treatment for bronchopulmonary sequestration.

  3. Mineral CO2 sequestration in alkaline solid residues

    International Nuclear Information System (INIS)

    Huijgen, W.J.J.; Comans, R.N.J.; Witkamp, G.J.

    2004-12-01

    Mineral carbonation is a promising sequestration route for the permanent and safe storage of carbon dioxide. In addition to calcium- or magnesium-containing primary minerals, suitable alkaline solid residues can be used as feedstock. The use of alkaline residues has several advantages, such as their availability close to CO2 sources and their higher reactivity for carbonation than primary minerals. In addition, the environmental quality of residues can potentially be improved by carbonation. In this study, key factors of the mineral CO2 sequestration process are identified, their influence on the carbonation process is examined, and environmental properties of the reaction products with regard to their possible beneficial utilization are investigated. The use of alkaline solid residues forms a potentially attractive alternative for the first mineral sequestration plants

  4. Dynamics and climate change mitigation potential of soil organic carbon sequestration.

    Science.gov (United States)

    Sommer, Rolf; Bossio, Deborah

    2014-11-01

    When assessing soil organic carbon (SOC) sequestration and its climate change (CC) mitigation potential at global scale, the dynamic nature of soil carbon storage and interventions to foster it should be taken into account. Firstly, adoption of SOC-sequestration measures will take time, and reasonably such schemes could only be implemented gradually at large-scale. Secondly, if soils are managed as carbon sinks, then SOC will increase only over a limited time, up to the point when a new SOC equilibrium is reached. This paper combines these two processes and predicts potential SOC sequestration dynamics in agricultural land at global scale and the corresponding CC mitigation potential. Assuming that global governments would agree on a worldwide effort to gradually change land use practices towards turning agricultural soils into carbon sinks starting 2014, the projected 87-year (2014-2100) global SOC sequestration potential of agricultural land ranged between 31 and 64 Gt. This is equal to 1.9-3.9% of the SRES-A2 projected 87-year anthropogenic emissions. SOC sequestration would peak 2032-33, at that time reaching 4.3-8.9% of the projected annual SRES-A2 emission. About 30 years later the sequestration rate would have reduced by half. Thus, SOC sequestration is not a C wedge that could contribute increasingly to mitigating CC. Rather, the mitigation potential is limited, contributing very little to solving the climate problem of the coming decades. However, we deliberately did not elaborate on the importance of maintaining or increasing SOC for sustaining soil health, agro-ecosystem functioning and productivity; an issue of global significance that deserves proper consideration irrespectively of any potential additional sequestration of SOC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. The Midwest Regional Carbon Sequestration Partnership (MRCSP)

    Energy Technology Data Exchange (ETDEWEB)

    James J. Dooley; Robert Dahowski; Casie Davidson

    2005-12-01

    This final report summarizes the Phase I research conducted by the Midwest regional Carbon Sequestration Partnership (MRCSP). The Phase I effort began in October 2003 and the project period ended on September 31, 2005. The MRCSP is a public/private partnership led by Battelle with the mission of identifying the technical, economic, and social issues associated with implementation of carbon sequestration technologies in its seven state geographic region (Indiana, Kentucky, Maryland, Michigan, Ohio, Pennsylvania, and West Virginia) and identifying viable pathways for their deployment. It is one of seven partnerships that together span most of the U.S. and parts of Canada that comprise the U.S. Department of Energy's (DOE's) Regional Carbon Sequestration Program led by DOE's national Energy Technology Laboratory (NETL). The MRCSP Phase I research was carried out under DOE Cooperative Agreement No. DE-FC26-03NT41981. The total value of Phase I was $3,513,513 of which the DOE share was $2,410,967 or 68.62%. The remainder of the cost share was provided in varying amounts by the rest of the 38 members of MRCSP's Phase I project. The next largest cost sharing participant to DOE in Phase I was the Ohio Coal Development Office within the Ohio Air Quality Development Authority (OCDO). OCDO's contribution was $100,000 and was contributed under Grant Agreement No. CDO/D-02-17. In this report, the MRCSP's research shows that the seven state MRCSP region is a major contributor to the U. S. economy and also to total emissions of CO2, the most significant of the greenhouse gases thought to contribute to global climate change. But, the research has also shown that the region has substantial resources for sequestering carbon, both in deep geological reservoirs (geological sequestration) and through improved agricultural and land management practices (terrestrial sequestration). Geological reservoirs, especially deep saline reservoirs, offer the potential

  6. Cost evaluation of CO2 sequestration by aqueous mineral carbonation

    International Nuclear Information System (INIS)

    Huijgen, Wouter J.J.; Comans, Rob N.J.; Witkamp, Geert-Jan

    2007-01-01

    A cost evaluation of CO 2 sequestration by aqueous mineral carbonation has been made using either wollastonite (CaSiO 3 ) or steel slag as feedstock. First, the process was simulated to determine the properties of the streams as well as the power and heat consumption of the process equipment. Second, a basic design was made for the major process equipment, and total investment costs were estimated with the help of the publicly available literature and a factorial cost estimation method. Finally, the sequestration costs were determined on the basis of the depreciation of investments and variable and fixed operating costs. Estimated costs are 102 and 77 EUR/ton CO 2 net avoided for wollastonite and steel slag, respectively. For wollastonite, the major costs are associated with the feedstock and the electricity consumption for grinding and compression (54 and 26 EUR/ton CO 2 avoided, respectively). A sensitivity analysis showed that additional influential parameters in the sequestration costs include the liquid-to-solid ratio in the carbonation reactor and the possible value of the carbonated product. The sequestration costs for steel slag are significantly lower due to the absence of costs for the feedstock. Although various options for potential cost reduction have been identified, CO 2 sequestration by current aqueous carbonation processes seems expensive relative to other CO 2 storage technologies. The permanent and inherently safe sequestration of CO 2 by mineral carbonation may justify higher costs, but further cost reductions are required, particularly in view of (current) prices of CO 2 emission rights. Niche applications of mineral carbonation with a solid residue such as steel slag as feedstock and/or a useful carbonated product hold the best prospects for an economically feasible CO 2 sequestration process. (author)

  7. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  8. Integrated Mid-Continent Carbon Capture, Sequestration & Enhanced Oil Recovery Project

    Energy Technology Data Exchange (ETDEWEB)

    Brian McPherson

    2010-08-31

    A consortium of research partners led by the Southwest Regional Partnership on Carbon Sequestration and industry partners, including CAP CO2 LLC, Blue Source LLC, Coffeyville Resources, Nitrogen Fertilizers LLC, Ash Grove Cement Company, Kansas Ethanol LLC, Headwaters Clean Carbon Services, Black & Veatch, and Schlumberger Carbon Services, conducted a feasibility study of a large-scale CCS commercialization project that included large-scale CO{sub 2} sources. The overall objective of this project, entitled the 'Integrated Mid-Continent Carbon Capture, Sequestration and Enhanced Oil Recovery Project' was to design an integrated system of US mid-continent industrial CO{sub 2} sources with CO{sub 2} capture, and geologic sequestration in deep saline formations and in oil field reservoirs with concomitant EOR. Findings of this project suggest that deep saline sequestration in the mid-continent region is not feasible without major financial incentives, such as tax credits or otherwise, that do not exist at this time. However, results of the analysis suggest that enhanced oil recovery with carbon sequestration is indeed feasible and practical for specific types of geologic settings in the Midwestern U.S.

  9. A new look at ocean carbon remineralization for estimating deepwater sequestration

    DEFF Research Database (Denmark)

    Guidi, L.; Legendre, L.; Reygondeau, Gabriel

    2015-01-01

    provinces, where these estimates range between -50 and +100% of the commonly used globally uniform remineralization value. We apply the regionalized values to satellite-derived estimates of upper ocean POC export to calculate regionalized and ocean-wide deep carbon fluxes and sequestration. The resulting....... These results stress that variable remineralization and sequestration depth should be used to model ocean carbon sequestration and feedback on the atmosphere......The "biological carbon pump" causes carbon sequestration in deep waters by downward transfer of organic matter, mostly as particles. This mechanism depends to a great extent on the uptake of CO2 by marine plankton in surface waters and subsequent sinking of particulate organic carbon (POC) through...

  10. Modelisation du stock de biomasse et dynamique de sequestration ...

    African Journals Online (AJOL)

    Mots clés: Jatropha curcas, séquestration, carbone, Bénin, Afrique de l'Ouest. English Title: Biomass stock modeling and dynamics of mineral and carbon sequestration of Jatropha curcas L. under different soil types in Benin. English Abstract. In West Africa, carbon sequestration function of Jatropha curcas shrubs and their ...

  11. Development of a monoclonal antibody-based ELISA for the hedgehog inhibitors cyclopamine and cyclopamine-KAAD

    Science.gov (United States)

    Cyclopamine was isolated from Veratrum californicum and identified as the teratogen responsible for severe craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in central Idaho. More recently, cyclopamine was found to inhibit the hedgehog (Hh) signaling ...

  12. TSC1 and TSC2 regulate cilia length and canonical Hedgehog signaling via different mechanisms

    DEFF Research Database (Denmark)

    Rosengren, Thomas; Larsen, Lasse Jonsgaard; Pedersen, Lotte Bang

    2018-01-01

    Primary cilia are sensory organelles that coordinate multiple cellular signaling pathways, including Hedgehog (HH), Wingless/Int (WNT) and Transforming Growth Factor-β (TGF-β) signaling. Similarly, primary cilia have been implicated in regulation of mTOR signaling, in which Tuberous Sclerosis Com...

  13. [Life cycle of Gongylonema mucronatum Seurat, 1916, parasite of the African hedge-hog (author's transl)].

    Science.gov (United States)

    Quentin, J C; Seguignes, M

    1979-01-01

    The Gongylonematid Nematode parasite of the Tunisian hedge-hog has been identified as Gongylonema mucronatum Seurat, 1916. The infective larva has been obtained from Locusta migratoria as intermediate host. The larval characters of this Gongylonema link it to the species G. pulchrum.

  14. The United States Department of Energy's Regional Carbon Sequestration Partnerships Program Validation Phase.

    Science.gov (United States)

    Litynski, John T; Plasynski, Sean; McIlvried, Howard G; Mahoney, Christopher; Srivastava, Rameshwar D

    2008-01-01

    This paper reviews the Validation Phase (Phase II) of the Department of Energy's Regional Carbon Sequestration Partnerships initiative. In 2003, the U.S. Department of Energy created a nationwide network of seven Regional Carbon Sequestration Partnerships (RCSP) to help determine and implement the technology, infrastructure, and regulations most appropriate to promote carbon sequestration in different regions of the nation. The objectives of the Characterization Phase (Phase I) were to characterize the geologic and terrestrial opportunities for carbon sequestration; to identify CO(2) point sources within the territories of the individual partnerships; to assess the transportation infrastructure needed for future deployment; to evaluate CO(2) capture technologies for existing and future power plants; and to identify the most promising sequestration opportunities that would need to be validated through a series of field projects. The Characterization Phase was highly successful, with the following achievements: established a national network of companies and professionals working to support sequestration deployment; created regional and national carbon sequestration atlases for the United States and portions of Canada; evaluated available and developing technologies for the capture of CO(2) from point sources; developed an improved understanding of the permitting requirements that future sequestration activities will need to address as well as defined the gap in permitting requirements for large scale deployment of these technologies; created a raised awareness of, and support for, carbon sequestration as a greenhouse gas (GHG) mitigation option, both within industry and among the general public; identified the most promising carbon sequestration opportunities for future field tests; and established protocols for project implementation, accounting, and management. Economic evaluation was started and is continuing and will be a factor in project selection. During the

  15. Anthropogenic nitrogen deposition enhances carbon sequestration in boreal soils.

    Science.gov (United States)

    Maaroufi, Nadia I; Nordin, Annika; Hasselquist, Niles J; Bach, Lisbet H; Palmqvist, Kristin; Gundale, Michael J

    2015-08-01

    It is proposed that carbon (C) sequestration in response to reactive nitrogen (Nr ) deposition in boreal forests accounts for a large portion of the terrestrial sink for anthropogenic CO2 emissions. While studies have helped clarify the magnitude by which Nr deposition enhances C sequestration by forest vegetation, there remains a paucity of long-term experimental studies evaluating how soil C pools respond. We conducted a long-term experiment, maintained since 1996, consisting of three N addition levels (0, 12.5, and 50 kg N ha(-1) yr(-1) ) in the boreal zone of northern Sweden to understand how atmospheric Nr deposition affects soil C accumulation, soil microbial communities, and soil respiration. We hypothesized that soil C sequestration will increase, and soil microbial biomass and soil respiration will decrease, with disproportionately large changes expected compared to low levels of N addition. Our data showed that the low N addition treatment caused a non-significant increase in the organic horizon C pool of ~15% and a significant increase of ~30% in response to the high N treatment relative to the control. The relationship between C sequestration and N addition in the organic horizon was linear, with a slope of 10 kg C kg(-1) N. We also found a concomitant decrease in total microbial and fungal biomasses and a ~11% reduction in soil respiration in response to the high N treatment. Our data complement previous data from the same study system describing aboveground C sequestration, indicating a total ecosystem sequestration rate of 26 kg C kg(-1) N. These estimates are far lower than suggested by some previous modeling studies, and thus will help improve and validate current modeling efforts aimed at separating the effect of multiple global change factors on the C balance of the boreal region. © 2015 John Wiley & Sons Ltd.

  16. Intralobar bronchopulmonary sequestration in the newborn - a congenital malformation

    International Nuclear Information System (INIS)

    Laurin, S.; Haegerstrand, I.

    1999-01-01

    Background. Intralobar sequestration (ILS) has been suggested to be an acquired lesion. However, we have observed several young infants who had ILS. Objectives. Since this fact seems to indicate a congenital origin, we reviewed our experience. Material and methods. A retrospective review of bronchopulmonary sequestration from the Departments of Radiology and Pathology in Lund between 1964 and 1997. Results. We identified seven infants or young children with a diagnosis of intralobar sequestration. In each patient, the ILS was present before recurrent infection developed. Five had chest X-rays as neonates, one at 3 months and one at 11 months of age. All but one showed an abnormality on their first chest X-ray, consistent with sequestration. Six of the ILS were verified at angiography; all seven were surgically removed. Two of the children with ILS also had congenital cystic adenomatoid malformation (CCAM). Three children had both ILS and scimitar syndrome. Conclusions. The fact that ILS was present in seven newborn and young infants indicates that this lesion is, at least in some patients, a congenital malformation. (orig.)

  17. 75 FR 33613 - Notice of the Carbon Sequestration-Geothermal Energy-Science Joint Workshop

    Science.gov (United States)

    2010-06-14

    ... Energy, DOE. ACTION: Notice of the Carbon Sequestration--Geothermal Energy--Science Joint Workshop... Fossil Energy-Carbon Sequestration Program will be holding a joint workshop on Common Research Themes for...-- http://www.geothermal.energy.gov . DATES: The Carbon Sequestration--Geothermal Energy--Science Joint...

  18. Southwestern Regional Partnership For Carbon Sequestration (Phase 2): Pump Canyon CO2-ECBM/Sequestration Demonstration, San Juan Basin, New Mexico

    International Nuclear Information System (INIS)

    2010-01-01

    Within the Southwest Regional Partnership on Carbon Sequestration (SWP), three demonstrations of geologic CO 2 sequestration are being performed -- one in an oilfield (the SACROC Unit in the Permian basin of west Texas), one in a deep, unmineable coalbed (the Pump Canyon site in the San Juan basin of northern New Mexico), and one in a deep, saline reservoir (underlying the Aneth oilfield in the Paradox basin of southeast Utah). The Pump Canyon CO 2 -enhanced coalbed methane (CO 2 /ECBM) sequestration demonstration project plans to demonstrate the effectiveness of CO 2 sequestration in deep, unmineable coal seams via a small-scale geologic sequestration project. The site is located in San Juan County, northern New Mexico, just within the limits of the high-permeability fairway of prolific coalbed methane production. The study area for the SWP project consists of 31 coalbed methane production wells located in a nine section area. CO 2 was injected continuously for a year and different monitoring, verification and accounting (MVA) techniques were implemented to track the CO 2 movement inside and outside the reservoir. Some of the MVA methods include continuous measurement of injection volumes, pressures and temperatures within the injection well, coalbed methane production rates, pressures and gas compositions collected at the offset production wells, and tracers in the injected CO 2 . In addition, time-lapse vertical seismic profiling (VSP), surface tiltmeter arrays, a series of shallow monitoring wells with a regular fluid sampling program, surface measurements of soil composition, CO 2 fluxes, and tracers were used to help in tracking the injected CO 2 . Finally, a detailed reservoir model was constructed to help reproduce and understand the behavior of the reservoir under production and injection operation. This report summarizes the different phases of the project, from permitting through site closure, and gives the results of the different MVA techniques.

  19. Simulating carbon sequestration using cellular automata and land use assessment for Karaj, Iran

    Science.gov (United States)

    Khatibi, Ali; Pourebrahim, Sharareh; Mokhtar, Mazlin Bin

    2018-06-01

    Carbon sequestration has been proposed as a means of slowing the atmospheric and marine accumulation of greenhouse gases. This study used observed and simulated land use/cover changes to investigate and predict carbon sequestration rates in the city of Karaj. Karaj, a metropolis of Iran, has undergone rapid population expansion and associated changes in recent years, and these changes make it suitable for use as a case study for rapidly expanding urban areas. In particular, high quality agricultural space, green space and gardens have rapidly transformed into industrial, residential and urban service areas. Five classes of land use/cover (residential, agricultural, rangeland, forest and barren areas) were considered in the study; vegetation and soil samples were taken from 20 randomly selected locations. The level of carbon sequestration was determined for the vegetation samples by calculating the amount of organic carbon present using the dry plant weight method, and for soil samples by using the method of Walkley and Black. For each area class, average values of carbon sequestration in vegetation and soil samples were calculated to give a carbon sequestration index. A cellular automata approach was used to simulate changes in the classes. Finally, the carbon sequestration indices were combined with simulation results to calculate changes in carbon sequestration for each class. It is predicted that, in the 15 year period from 2014 to 2029, much agricultural land will be transformed into residential land, resulting in a severe reduction in the level of carbon sequestration. Results from this study indicate that expansion of forest areas in urban counties would be an effective means of increasing the levels of carbon sequestration. Finally, future opportunities to include carbon sequestration into the simulation of land use/cover changes are outlined.

  20. Treatment for unstable pulmonary sequestration injury in patient with severe blunt trauma: A case report

    Directory of Open Access Journals (Sweden)

    Sakiko Hiraki

    2017-08-01

    Full Text Available Case: Pulmonary sequestration is a congenital malformation characterized by nonfunctioning tissue not communicating with the tracheobronchial tree. As the blood pressure in the artery feeding the sequestrated lung tissue is higher than that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary sequestration is high. We herein present the first case of a severe blunt trauma patient with unstable pulmonary sequestration injury. Outcome and conclusion: The mechanism of pulmonary sequestration injury is vastly different than that of injury to normal lung. We suggest that proximal feeding artery embolization should be performed before surgical intervention in patients with massive hemorrhage of pulmonary sequestration due to severe chest trauma. Keywords: Blunt trauma, Coil embolization, Massive hemorrhage, Pulmonary sequestration

  1. Tailings and mineral carbonation : the potential for atmospheric CO{sub 2} sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Rollo, H.A. [Lorax Environmental Services Ltd., Vancouver, BC (Canada); Jamieson, H.E. [Queen' s Univ., Kingston, ON (Canada). Dept. of Geological Sciences and Geological Engineering; Lee, C.A. [Dillon Consulting Ltd., Cambridge, ON (Canada)

    2009-02-15

    Carbon dioxide (CO{sub 2}) sequestration includes geological storage, ocean storage, organic storage, and mineral storage (mineral carbonation). This presentation discussed tailings and mineral carbonation and the potential for atmospheric CO{sub 2} sequestration. In particular, it outlined CO{sub 2} sequestration and presented a history of investigations. The Ekati Diamond Mine was discussed with particular reference to its location, geology, and processing. Other topics that were presented included mineralogy; water chemistry; modeling results; and estimates of annual CO{sub 2} sequestration. Conclusions and implications were also presented. It was concluded that ore processing at mines with ultramafic host rocks have the potential to partially offset CO{sub 2} emissions. In addition, it was found that existing tailings at ultramafic deposits may be viable source materials for CO{sub 2} sequestration by mineral carbonation. tabs., figs.

  2. Ligands specify estrogen receptor alpha nuclear localization and degradation

    Directory of Open Access Journals (Sweden)

    Caze-Subra Stéphanie

    2010-12-01

    Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

  3. Anticancer drugs and the regulation of Hedgehog genes GLI1 and PTCH1, a comparative study in nonmelanoma skin cancer cell lines

    DEFF Research Database (Denmark)

    Olesen, Uffe H; Bojesen, Sophie; Gehl, Julie

    2017-01-01

    Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin...... of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines. The impact of treatment on the regulation of Hedgehog pathway target genes (GLI1 and PTCH1), measured by real-time PCR, was compared between UWBCC1 and HaCaT. Varying cell line sensitivity profiles...... to the examined anticancer drugs were observed. Generally, 24-h drug exposure was sufficient to reduce cell viability. We found that 5-FU, MTX, and cisplatin significantly downregulated the expression of two genes controlled by the Hedgehog pathway (≤25-, 2.9-, and 12.5-fold, respectively, for GLI1 in UWBCC1...

  4. Effects of sulfate ligand on uranyl carbonato surface species on ferrihydrite surfaces.

    Science.gov (United States)

    Arai, Yuji; Fuller, C C

    2012-01-01

    Understanding uranium (U) sorption processes in permeable reactive barriers (PRB) are critical in modeling reactive transport for evaluating PRB performance at the Fry Canyon demonstration site in Utah, USA. To gain insight into the U sequestration mechanism in the amorphous ferric oxyhydroxide (AFO)-coated gravel PRB, U(VI) sorption processes on ferrihydrite surfaces were studied in 0.01 M Na(2)SO(4) solutions to simulate the major chemical composition of U-contaminated groundwater (i.e., [SO(4)(2-)] ~13 mM L(-1)) at the site. Uranyl sorption was greater at pH 7.5 than that at pH 4 in both air- and 2% pCO(2)-equilibrated systems. While there were negligible effects of sulfate ligands on the pH-dependent U(VI) sorption (carbonato U(VI) ternary surface species became more important. At 2% pCO(2), there was no contribution of sulfate ligands on the U(VI) ternary surface species. Instead, a mixture of bis-carbonato inner-sphere (38%) and tris-carbonato outer-sphere U(VI) ternary surface species (62%) was found at pH 7.62. The study suggests that the competitive ligand (bicarbonate and sulfate) coordination on U(VI) surface species might be important in evaluating the U solid-state speciation in the AFO PRB at the study site where pCO(2) fluctuates between 1 and 2 pCO(2)%. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Comprehensive analysis of gene expression patterns of hedgehog-related genes

    Directory of Open Access Journals (Sweden)

    Baillie David

    2006-10-01

    Full Text Available Abstract Background The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity with the Hedgehog signaling molecule through their C-terminal autoprocessing Hint/Hog domain. These proteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteins containing only these N-terminal domains. These gene families are called warthog, groundhog, ground-like and quahog, collectively called hedgehog (hh-related genes. Previously, the expression pattern of seventeen genes was examined, which showed that they are primarily expressed in the ectoderm. Results With the completion of the C. elegans genome sequence in November 2002, we reexamined and identified 61 hh-related ORFs. Further, we identified 49 hh-related ORFs in C. briggsae. ORF analysis revealed that 30% of the genes still had errors in their predictions and we improved these predictions here. We performed a comprehensive expression analysis using GFP fusions of the putative intergenic regulatory sequence with one or two transgenic lines for most genes. The hh-related genes are expressed in one or a few of the following tissues: hypodermis, seam cells, excretory duct and pore cells, vulval epithelial cells, rectal epithelial cells, pharyngeal muscle or marginal cells, arcade cells, support cells of sensory organs, and neuronal cells. Using time-lapse recordings, we discovered that some hh-related genes are expressed in a cyclical fashion in phase with molting during larval development. We also generated several translational GFP fusions, but they did not show any subcellular localization. In addition, we also studied the expression patterns of two genes with similarity to Drosophila frizzled, T23D8.1 and F27E11.3A, and the ortholog of the Drosophila gene dally-like, gpn-1, which is a heparan sulfate proteoglycan. The two frizzled homologs are expressed in a few neurons in the head, and gpn-1 is expressed in the pharynx. Finally, we compare the

  6. Environmental Externalities of Geological Carbon Sequestration Effects on Energy Scenarios

    International Nuclear Information System (INIS)

    Smekens, K.; Van der Zwaan, B.

    2004-03-01

    Geological carbon sequestration seems one of the promising options to address, in the near term, the global problem of climate change, since carbon sequestration technologies are in principle available today and their costs are expected to be affordable. Whereas extensive technological and economic feasibility studies rightly point out the large potential of this 'clean fossil fuel' option, relatively little attention has been paid so far to the detrimental environmental externalities that the sequestering of CO2 underground could entail. This paper assesses what the relevance might be of including these external effects in long-term energy planning and scenario analyses. Our main conclusion is that, while these effects are generally likely to be relatively small, carbon sequestration externalities do matter and influence the nature of future world energy supply and consumption. More importantly, since geological carbon storage (depending on the method employed) may in some cases have substantial external impacts, in terms of both environmental damage and health risks, it is recommended that extensive studies are performed to quantify these effects. This article addresses three main questions: (1) What may energy supply look like if one accounts for large-scale CO2 sequestration in the construction of long-term energy and climate change scenarios; (2) Suppose one hypothesizes a quantification of the external environmental costs of CO2 sequestration, how do then these supposed costs affect the evolution of the energy system during the 21st century; (3) Does it matter for these scenarios whether carbon sequestration damage costs are charged directly to consumers or, instead, to electricity producers?

  7. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. [Seagrass ecosystems: contributions to and mechanisms of carbon sequestration].

    Science.gov (United States)

    Qiu, Guang-Long; Lin, Hsing-Juh; Li, Zong-Shan; Fan, Hang-Qing; Zhou, Hao-Lang; Liu, Guo-Hua

    2014-06-01

    The ocean's vegetated habitats, in particular seagrasses, mangroves and salt marshes, each capture and store a comparable amount of carbon per year, forming the Earth's blue carbon sinks, the most intense carbon sinks on the planet. Seagrass meadows, characterized by high primary productivity, efficient water column filtration and sediment stability, have a pronounced capacity for carbon sequestration. This is enhanced by low decomposition rates in anaerobic seagrass sediments. The carbon captured by seagrass meadows contributes significantly to the total blue carbon. At a global scale, seagrass ecosystems are carbon sink hot spots and have profound influences on the global carbon cycle. This importance combined with the many other functions of seagrass meadows places them among the most valuable ecosystems in the world. Unfortunately, seagrasses are declining globally at an alarming rate owing to anthropogenic disturbances and climate change, making them also among the most threatened ecosystems on the Earth. The role of coastal systems in carbon sequestration has received far too little attention and thus there are still many uncertainties in evaluating carbon sequestration of global seagrass meadows accurately. To better assess the carbon sequestration of global seagrass ecosystems, a number of scientific issues should be considered with high priorities: 1) more accurate measurements of seagrass coverage at national and global levels; 2) more comprehensive research into species- and location-specific carbon sequestration efficiencies; 3) in-depth exploration of the effects of human disturbance and global climate change on carbon capture and storage by seagrass ecosystems.

  9. Growth of limb muscle is dependent on skeletal-derived Indian hedgehog

    OpenAIRE

    Bren-Mattison, Yvette; Hausburg, Melissa; Olwin, Bradley B.

    2011-01-01

    During embryogenesis, muscle and bone develop in close temporal and spatial proximity. We show that Indian Hedgehog, a bone-derived signaling molecule, participates in growth of skeletal muscle. In Ihh−/− embryos, skeletal muscle development appears abnormal at embryonic day 14.5 and at later ages through embryonic day 20.5, dramatic losses of hindlimb muscle occur. To further examine the role of Ihh in myogenesis, we manipulated Ihh expression in the developing chick hindlimb. Reduction of I...

  10. Carbon capture and sequestration (CCS)

    Science.gov (United States)

    2009-06-19

    Carbon capture and sequestration (or storage)known as CCShas attracted interest as a : measure for mitigating global climate change because large amounts of carbon dioxide (CO2) : emitted from fossil fuel use in the United States are potentiall...

  11. Possible impacts of sequestration on federal research

    Science.gov (United States)

    Showstack, Randy

    2012-10-01

    U.S. federal research and development (R&D) activities could be reduced by up to $57.5 billion, or 8.4%, through 2017 because of automatic reductions in U.S. federal funding, referred to as sequestration, that are set to begin in January 2013 under the 2011 Budget Control Act. That is according to a 27 September analysis by the American Association for the Advancement of Science (AAAS). If defense R&D is pulled from the equation, sequestration could cut nondefense R&D by $50.8 billion, or 17.2% through that same time period, according to AAAS. Under an equal allocation scenario, the Department of Energy could lose $4.6 billion for R&D over that time period, the National Science Foundation could lose $2.1 billion for R&D, and NASA could lose $3.5 billion, according to the analysis, which also notes that states could be hit hard by decreased federal R&D spending. Congressional leaders currently are looking into how to avoid sequestration. For more information, see http://www.aaas.org/news/releases/2012/0928sequester.shtml.

  12. Maintenance of a living understory enhances soil carbon sequestration in subtropical orchards.

    Science.gov (United States)

    Liu, Zhanfeng; Lin, Yongbiao; Lu, Hongfang; Ding, Mingmao; Tan, Yaowen; Xu, Shejin; Fu, Shenglei

    2013-01-01

    Orchard understory represents an important component of the orchards, performing numerous functions related to soil quality, water relations and microclimate, but little attention has been paid on its effect on soil C sequestration. In the face of global climate change, fruit producers also require techniques that increase carbon (C) sequestration in a cost-effective manner. Here we present a case study to compare the effects of understory management (sod culture vs. clean tillage) on soil C sequestration in four subtropical orchards. The results of a 10-year study indicated that the maintenance of sod significantly enhanced the soil C stock in the top 1 m of orchard soils. Relative to clean tillage, sod culture increased annual soil C sequestration by 2.85 t C ha(-1), suggesting that understory management based on sod culture offers promising potential for soil carbon sequestration. Considering that China has the largest area of orchards in the world and that few of these orchards currently have sod understories, the establishment and maintenance of sod in orchards can help China increase C sequestration and greatly contribute to achieving CO2 reduction targets at a regional scale and potentially at a national scale.

  13. Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development

    OpenAIRE

    Jenkins, Dagan; Winyard, Paul J D; Woolf, Adrian S.

    2007-01-01

    Studies of mouse mutants have demonstrated that Sonic hedgehog (SHH) signalling has a functional role in morphogenesis and differentiation at multiple sites within the forming urinary tract, and urinary tract malformations have been reported in humans with mutations that disrupt SHH signalling. However, there is only strikingly sparse and fragmentary information about the expression of SHH and associated signalling genes in normal human urinary tract development. We used immunohistochemistry ...

  14. Treatment for unstable pulmonary sequestration injury in patient with severe blunt trauma: A case report.

    Science.gov (United States)

    Hiraki, Sakiko; Okada, Yohei; Arai, Yusuke; Ishii, Wataru; Iiduka, Ryoji

    2017-08-01

    Pulmonary sequestration is a congenital malformation characterized by nonfunctioning tissue not communicating with the tracheobronchial tree. As the blood pressure in the artery feeding the sequestrated lung tissue is higher than that in the normal pulmonary artery, the risk of massive hemorrhage in pulmonary sequestration is high. We herein present the first case of a severe blunt trauma patient with unstable pulmonary sequestration injury. The mechanism of pulmonary sequestration injury is vastly different than that of injury to normal lung. We suggest that proximal feeding artery embolization should be performed before surgical intervention in patients with massive hemorrhage of pulmonary sequestration due to severe chest trauma.

  15. Micromotor-Based Biomimetic Carbon Dioxide Sequestration: Towards Mobile Microscrubbers.

    Science.gov (United States)

    Uygun, Murat; Singh, Virendra V; Kaufmann, Kevin; Uygun, Deniz A; de Oliveira, Severina D S; Wang, Joseph

    2015-10-26

    We describe a mobile CO2 scrubbing platform that offers a greatly accelerated biomimetic sequestration based on a self-propelled carbonic anhydrase (CA) functionalized micromotor. The CO2 hydration capability of CA is coupled with the rapid movement of catalytic micromotors, and along with the corresponding fluid dynamics, results in a highly efficient mobile CO2 scrubbing microsystem. The continuous movement of CA and enhanced mass transport of the CO2 substrate lead to significant improvements in the sequestration efficiency and speed over stationary immobilized or free CA platforms. This system is a promising approach to rapid and enhanced CO2 sequestration platforms for addressing growing concerns over the buildup of greenhouse gas. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. BIG SKY CARBON SEQUESTRATION PARTNERSHIP

    Energy Technology Data Exchange (ETDEWEB)

    Susan M. Capalbo

    2005-01-31

    The Big Sky Carbon Sequestration Partnership, led by Montana State University, is comprised of research institutions, public entities and private sectors organizations, and the Confederated Salish and Kootenai Tribes and the Nez Perce Tribe. Efforts under this Partnership in Phase I fall into four areas: evaluation of sources and carbon sequestration sinks that will be used to determine the location of pilot demonstrations in Phase II; development of GIS-based reporting framework that links with national networks; designing an integrated suite of monitoring, measuring, and verification technologies and assessment frameworks; and initiating a comprehensive education and outreach program. The groundwork is in place to provide an assessment of storage capabilities for CO{sub 2} utilizing the resources found in the Partnership region (both geological and terrestrial sinks), that would complement the ongoing DOE research. Efforts are underway to showcase the architecture of the GIS framework and initial results for sources and sinks. The region has a diverse array of geological formations that could provide storage options for carbon in one or more of its three states. Likewise, initial estimates of terrestrial sinks indicate a vast potential for increasing and maintaining soil C on forested, agricultural, and reclaimed lands. Both options include the potential for offsetting economic benefits to industry and society. Steps have been taken to assure that the GIS-based framework is consistent among types of sinks within the Big Sky Partnership area and with the efforts of other western DOE partnerships. The Partnership recognizes the critical importance of measurement, monitoring, and verification technologies to support not only carbon trading but all policies and programs that DOE and other agencies may want to pursue in support of GHG mitigation. The efforts in developing and implementing MMV technologies for geological sequestration reflect this concern. Research is

  17. Loss of Indian Hedgehog activates multiple aspects of a wound healing response in the mouse intestine

    NARCIS (Netherlands)

    van Dop, Willemijn A.; Heijmans, Jarom; Büller, Nikè V. J. A.; Snoek, Susanne A.; Rosekrans, Sanne L.; Wassenberg, Elisabeth A.; van den Bergh Weerman, Marius A.; Lanske, Beate; Clarke, Alan R.; Winton, Douglas J.; Wijgerde, Mark; Offerhaus, G. Johan; Hommes, Daan W.; Hardwick, James C.; de Jonge, Wouter J.; Biemond, Izak; van den Brink, Gijs R.

    2010-01-01

    Indian Hedgehog (Ihh) is expressed by the differentiated epithelial cells of the small intestine and signals to the mesenchyme where it induces unidentified factors that negatively regulate intestinal epithelial precursor cell fate. Recently, genetic variants in the Hh pathway have been linked to

  18. [Research methods of carbon sequestration by soil aggregates: a review].

    Science.gov (United States)

    Chen, Xiao-Xia; Liang, Ai-Zhen; Zhang, Xiao-Ping

    2012-07-01

    To increase soil organic carbon content is critical for maintaining soil fertility and agricultural sustainable development and for mitigating increased greenhouse gases and the effects of global climate change. Soil aggregates are the main components of soil, and have significant effects on soil physical and chemical properties. The physical protection of soil organic carbon by soil aggregates is the important mechanism of soil carbon sequestration. This paper reviewed the organic carbon sequestration by soil aggregates, and introduced the classic and current methods in studying the mechanisms of carbon sequestration by soil aggregates. The main problems and further research trends in this study field were also discussed.

  19. Regulating forest rotation to increase CO{sub 2} sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Gong, P.; Kristroem, B.

    1999-06-01

    Previous studies have shown that the optimal forest rotation age increases considerably if the benefits of CO{sub 2} sequestration are included in rotation decisions. While these studies provide some guidelines for managing public forests, private forest owners may not choose the socially optimal rotation age. This paper discusses a regulation measure to increase CO{sub 2} sequestration in privately owned forests. The regulation problem is treated as a sequential game, where the regulator chooses a subsidy scheme and forest owners respond by changing rotation ages. A private forest owner receives a subsidy at the time of harvesting if he/she changes the rotation age towards the socially optimal one. The subsidy is proportional to the associated change in timber yield. The forest owner`s objective is to maximize the net present value of after-tax timber production profits and subsidies. The regulator`s decision problem is to find the subsidy rate that maximizes the net benefits of implementing the policy (the net of increased CO{sub 2} sequestration benefits, subsidy costs, and changes in forestry taxation income). Empirical results for Swedish examples show that the optimal subsidy rate is sensitive to the marginal benefit of CO{sub 2} sequestration, the social discount rate, and site quality. The optimal subsidy rate is found to be significantly lower than the marginal benefit of CO{sub 2} sequestration. With the proposed subsidy scheme, private forest owners will choose rotation ages longer than the Faustmann rotation, but significantly shorter than the socially optimal rotation age 21 refs, 6 tabs. Arbetsrapport 272

  20. CO2 Sequestration short course

    Energy Technology Data Exchange (ETDEWEB)

    DePaolo, Donald J. [Lawrence Berkeley National Laboratory; Cole, David R [The Ohio State University; Navrotsky, Alexandra [University of California-Davis; Bourg, Ian C [Lawrence Berkeley National Laboratory

    2014-12-08

    Given the public’s interest and concern over the impact of atmospheric greenhouse gases (GHGs) on global warming and related climate change patterns, the course is a timely discussion of the underlying geochemical and mineralogical processes associated with gas-water-mineral-interactions encountered during geological sequestration of CO2. The geochemical and mineralogical processes encountered in the subsurface during storage of CO2 will play an important role in facilitating the isolation of anthropogenic CO2 in the subsurface for thousands of years, thus moderating rapid increases in concentrations of atmospheric CO2 and mitigating global warming. Successful implementation of a variety of geological sequestration scenarios will be dependent on our ability to accurately predict, monitor and verify the behavior of CO2 in the subsurface. The course was proposed to and accepted by the Mineralogical Society of America (MSA) and The Geochemical Society (GS).

  1. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    Directory of Open Access Journals (Sweden)

    Fecher LA

    2015-11-01

    Full Text Available Leslie A Fecher,1,3 William H Sharfman2 1Department of Internal Medicine and Dermatology, Indiana University Health Simon Cancer Center, Indianapolis, IN, USA; 2The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 3Department of Internal Medicine and Dermatology, University of Michigan, MI, USA Abstract: Cutaneous basal cell carcinoma (BCC is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449, a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. Keywords: basal cell carcinoma, hedgehog, smoothened, vismodegib, Gorlin, basal cell nevus syndrome

  2. Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas

    International Nuclear Information System (INIS)

    Zhu Weiguo; You Zhenbin; Li Tao; Yu Changhua; Tao Guangzhou; Hu Mingli; Chen Xiaofei

    2011-01-01

    The objective of this study was to investigate the significance of hedgehog signaling pathway in chemoradiotherapy sensitivity and its effect on the prognosis of esophageal squamous cell carcinoma. In the present study, we used the method of immunohistochemistry to examine the expression status of two hedgehog components, PTCH1 and glioma-associated oncogene GLI-1, in 100 pre-treated biopsy specimens of esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. We find that high levels of PTCH1 and GLI-1 were detected in 76.0 and 72.0% of esophageal squamous cell carcinoma, respectively. Significant associations of high PTCH1 and GLI-1 expression with large tumor size (both P=0.01), locoregional progression (P=0.001 and 0.003, respectively) and the lack of complete response to chemoradiotherapy (P=0.008 and 0.01, respectively) were observed. Univariate analysis revealed that high PTCH1 and GLI-1 expression was associated with poor locoregional progression-free survival, distant progression-free survival and overall survival. Furthermore, esophageal squamous cell carcinoma patients with high PTCH1 and GLI-1 expression have the shorter survival time than the subgroups with negative and low PTCH1 and GLI-1 expression. In multivariate analysis, PTCH1 and GLI-1 expression status were both evaluated as independent prognostic factors for locoregional progression-free survival, distant progression-free survival and overall survival. These findings suggest an important role for the activation of hedgehog signaling in esophageal squamous cell carcinoma progression and that PTCH1 and GLI-1 expression may be significantly associated with esophageal squamous cell carcinoma resistance to chemoradiotherapy. (author)

  3. Energy consumption and net CO2 sequestration of aqueous mineral carbonation

    International Nuclear Information System (INIS)

    Huijgen, W.J.J.; Ruijg, G.J.; Comans, R.N.J.; Witkamp, G.J.

    2006-12-01

    Aqueous mineral carbonation is a potentially attractive sequestration technology to reduce CO2 emissions. The energy consumption of this technology, however, reduces the net amount of CO2 sequestered. Therefore, the energetic CO2 sequestration efficiency of aqueous mineral carbonation was studied in dependence of various process variables using either wollastonite (CaSiO3) or steel slag as feedstock. For wollastonite, the maximum energetic CO2 sequestration efficiency within the ranges of process conditions studied was 75% at 200C, 20 bar CO2, and a particle size of <38μm. The main energy-consuming process steps were the grinding of the feedstock and the compression of the CO2 feed. At these process conditions, a significantly lower efficiency was determined for steel slag (69%), mainly because of the lower Ca content of the feedstock. The CO2 sequestration efficiency might be improved substantially for both types of feedstock by, e.g., reducing the amount of process water applied and further grinding of the feedstock. The calculated energetic efficiencies warrant a further assessment of the (energetic) feasibility of CO2 sequestration by aqueous mineral carbonation on the basis of a pilot-scale process

  4. GDC-0449-a potent inhibitor of the hedgehog pathway.

    Science.gov (United States)

    Robarge, Kirk D; Brunton, Shirley A; Castanedo, Georgette M; Cui, Yong; Dina, Michael S; Goldsmith, Richard; Gould, Stephen E; Guichert, Oivin; Gunzner, Janet L; Halladay, Jason; Jia, Wei; Khojasteh, Cyrus; Koehler, Michael F T; Kotkow, Karen; La, Hank; Lalonde, Rebecca L; Lau, Kevin; Lee, Leslie; Marshall, Derek; Marsters, James C; Murray, Lesley J; Qian, Changgeng; Rubin, Lee L; Salphati, Laurent; Stanley, Mark S; Stibbard, John H A; Sutherlin, Daniel P; Ubhayaker, Savita; Wang, Shumei; Wong, Susan; Xie, Minli

    2009-10-01

    SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC.

  5. Hedgehogs and sugar gliders: respiratory anatomy, physiology, and disease.

    Science.gov (United States)

    Johnson, Dan H

    2011-05-01

    This article discusses the respiratory anatomy, physiology, and disease of African pygmy hedgehogs (Atelerix albiventris) and sugar gliders (Petaurus breviceps), two species commonly seen in exotic animal practice. Where appropriate, information from closely related species is mentioned because cross-susceptibility is likely and because these additional species may also be encountered in practice. Other body systems and processes are discussed insofar as they relate to or affect respiratory function. Although some topics, such as special senses, hibernation, or vocalization, may seem out of place, in each case the information relates back to respiration in some important way. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Gli2a protein localization reveals a role for Iguana/DZIP1 in primary ciliogenesis and a dependence of Hedgehog signal transduction on primary cilia in the zebrafish

    Directory of Open Access Journals (Sweden)

    van Eeden Freek

    2010-04-01

    Full Text Available Abstract Background In mammalian cells, the integrity of the primary cilium is critical for proper regulation of the Hedgehog (Hh signal transduction pathway. Whether or not this dependence on the primary cilium is a universal feature of vertebrate Hedgehog signalling has remained contentious due, in part, to the apparent divergence of the intracellular transduction pathway between mammals and teleost fish. Results Here, using a functional Gli2-GFP fusion protein, we show that, as in mammals, the Gli2 transcription factor localizes to the primary cilia of cells in the zebrafish embryo and that this localization is modulated by the activity of the Hh pathway. Moreover, we show that the Igu/DZIP1protein, previously implicated in the modulation of Gli activity in zebrafish, also localizes to the primary cilium and is required for its proper formation. Conclusion Our findings demonstrate a conserved role of the primary cilium in mediating Hedgehog signalling activity across the vertebrate phylum and validate the use of the zebrafish as a representative model for the in vivo analysis of vertebrate Hedgehog signalling.

  7. Community perceptions of carbon sequestration: insights from California

    International Nuclear Information System (INIS)

    Wong-Parodi, Gabrielle; Ray, Isha

    2009-01-01

    Over the last decade, many energy experts have supported carbon sequestration as a viable technological response to climate change. Given the potential importance of sequestration in US energy policy, what might explain the views of communities that may be directly impacted by the siting of this technology? To answer this question, we conducted focus groups in two communities who were potentially pilot project sites for California's DOE-funded West Coast Regional Partnership (WESTCARB). We find that communities want a voice in defining the risks to be mitigated as well as the justice of the procedures by which the technology is implemented. We argue that a community's sense of empowerment is key to understanding its range of carbon sequestration opinions, where 'empowerment' includes the ability to mitigate community-defined risks of the technology. This sense of empowerment protects the community against the downside risk of government or corporate neglect, a risk that is rarely identified in risk assessments but that should be factored into assessment and communication strategies.

  8. Environmental non-government organizations' perceptions of geologic sequestration

    International Nuclear Information System (INIS)

    Wong-Parodi, Gabrielle; Ray, Isha; Farrell, Alexander E

    2008-01-01

    Environmental non-governmental organizations (NGOs) have been influential in shaping public perceptions of environmental problems, their causes and potential solutions. Over the last decade, carbon capture and storage (CCS) has emerged as a potentially important technological response to climate change. In this paper we investigate how leading US NGOs perceive geologic sequestration, a potentially controversial part of CCS. We examine how and why their perceptions and strategies might differ, and if and how they plan to shape public perceptions of geologic sequestration. We approach these questions through semi-structured interviews with representatives from a range of NGOs, supplemented by content analysis of their documents. We find that while all the NGOs are committed to combating climate change, their views on CCS as a mitigation strategy vary considerably. We find that these views are correlated with NGOs' histories of activism and advocacy, as well as with their sources of funding. Overall, most of these NGOs accept the necessity of geologic sequestration, while only a small fraction do not

  9. Southwestern Regional Partnership For Carbon Sequestration (Phase 2) Pump Canyon CO2- ECBM/Sequestration Demonstration, San Juan Basin, New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Advanced Resources International

    2010-01-31

    Within the Southwest Regional Partnership on Carbon Sequestration (SWP), three demonstrations of geologic CO{sub 2} sequestration are being performed -- one in an oilfield (the SACROC Unit in the Permian basin of west Texas), one in a deep, unmineable coalbed (the Pump Canyon site in the San Juan basin of northern New Mexico), and one in a deep, saline reservoir (underlying the Aneth oilfield in the Paradox basin of southeast Utah). The Pump Canyon CO{sub 2}-enhanced coalbed methane (CO{sub 2}/ECBM) sequestration demonstration project plans to demonstrate the effectiveness of CO{sub 2} sequestration in deep, unmineable coal seams via a small-scale geologic sequestration project. The site is located in San Juan County, northern New Mexico, just within the limits of the high-permeability fairway of prolific coalbed methane production. The study area for the SWP project consists of 31 coalbed methane production wells located in a nine section area. CO{sub 2} was injected continuously for a year and different monitoring, verification and accounting (MVA) techniques were implemented to track the CO{sub 2} movement inside and outside the reservoir. Some of the MVA methods include continuous measurement of injection volumes, pressures and temperatures within the injection well, coalbed methane production rates, pressures and gas compositions collected at the offset production wells, and tracers in the injected CO{sub 2}. In addition, time-lapse vertical seismic profiling (VSP), surface tiltmeter arrays, a series of shallow monitoring wells with a regular fluid sampling program, surface measurements of soil composition, CO{sub 2} fluxes, and tracers were used to help in tracking the injected CO{sub 2}. Finally, a detailed reservoir model was constructed to help reproduce and understand the behavior of the reservoir under production and injection operation. This report summarizes the different phases of the project, from permitting through site closure, and gives the

  10. ANALYSIS OF URBAN FOREST CARBON SEQUESTRATION CAPACITY: A CASE STUDY OF ZENGDU, SUIZHOU

    Directory of Open Access Journals (Sweden)

    X. Yu

    2017-09-01

    Full Text Available Carbon-fixing and oxygen-releasing is an important content of forest ecosystem serving in city. Analysis of forest ecosystem carbon sequestration capacity can provide scientific reference for urban forest management strategies. Taking Zengdu of Suizhou as an example, CITYGREEN model was applied to calculate the carbon sequestration benefits of urban forest ecosystem in this paper. And the carbon sequestration potential of urban forest ecosystem following the returning of farmland to forest land is also evaluated. The results show that forest area, percent tree cover, and the structure of forest land were the major factors reflecting regional carbon sequestration capacity.

  11. The biodiversity cost of carbon sequestration in tropical savanna

    OpenAIRE

    Abreu, Rodolfo C. R.; Hoffmann, William A.; Vasconcelos, Heraldo L.; Pilon, Natashi A.; Rossatto, Davi R.; Durigan, Giselda

    2017-01-01

    Tropical savannas have been increasingly viewed as an opportunity for carbon sequestration through fire suppression and afforestation, but insufficient attention has been given to the consequences for biodiversity. To evaluate the biodiversity costs of increasing carbon sequestration, we quantified changes in ecosystem carbon stocks and the associated changes in communities of plants and ants resulting from fire suppression in savannas of the Brazilian Cerrado, a global biodiversity hotspot. ...

  12. Torsed pulmonary sequestration presenting as a painful chest mass

    International Nuclear Information System (INIS)

    Shah, Ricki; Carver, Terrence W.; Rivard, Douglas C.

    2010-01-01

    Pulmonary sequestration is a congenital abnormality that can be divided into intralobar or extralobar types. Both types are characterized by pulmonary tissue that does not communicate with the bronchial tree or pulmonary arteries and typically has its arterial supply arising from the descending aorta. We report a case of an 11-year-old girl with extralobar sequestration who presented with torsion causing abdominal pain and pleuritic chest pain. (orig.)

  13. Carbon sequestration by Australian tidal marshes

    KAUST Repository

    Macreadie, Peter I.

    2017-03-10

    Australia\\'s tidal marshes have suffered significant losses but their recently recognised importance in CO2 sequestration is creating opportunities for their protection and restoration. We compiled all available data on soil organic carbon (OC) storage in Australia\\'s tidal marshes (323 cores). OC stocks in the surface 1 m averaged 165.41 (SE 6.96) Mg OC ha-1 (range 14-963 Mg OC ha-1). The mean OC accumulation rate was 0.55 ± 0.02 Mg OC ha-1 yr-1. Geomorphology was the most important predictor of OC stocks, with fluvial sites having twice the stock of OC as seaward sites. Australia\\'s 1.4 million hectares of tidal marshes contain an estimated 212 million tonnes of OC in the surface 1 m, with a potential CO2-equivalent value of $USD7.19 billion. Annual sequestration is 0.75 Tg OC yr-1, with a CO2-equivalent value of $USD28.02 million per annum. This study provides the most comprehensive estimates of tidal marsh blue carbon in Australia, and illustrates their importance in climate change mitigation and adaptation, acting as CO2 sinks and buffering the impacts of rising sea level. We outline potential further development of carbon offset schemes to restore the sequestration capacity and other ecosystem services provided by Australia tidal marshes.

  14. Integrating Steel Production with Mineral Carbon Sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Klaus Lackner; Paul Doby; Tuncel Yegulalp; Samuel Krevor; Christopher Graves

    2008-05-01

    The objectives of the project were (i) to develop a combination iron oxide production and carbon sequestration plant that will use serpentine ores as the source of iron and the extraction tailings as the storage element for CO2 disposal, (ii) the identification of locations within the US where this process may be implemented and (iii) to create a standardized process to characterize the serpentine deposits in terms of carbon disposal capacity and iron and steel production capacity. The first objective was not accomplished. The research failed to identify a technique to accelerate direct aqueous mineral carbonation, the limiting step in the integration of steel production and carbon sequestration. Objective (ii) was accomplished. It was found that the sequestration potential of the ultramafic resource surfaces in the US and Puerto Rico is approximately 4,647 Gt of CO2 or over 500 years of current US production of CO2. Lastly, a computer model was developed to investigate the impact of various system parameters (recoveries and efficiencies and capacities of different system components) and serpentinite quality as well as incorporation of CO2 from sources outside the steel industry.

  15. Development of Protective Coatings for Co-Sequestration Processes and Pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Bierwagen, Gordon; Huang, Yaping

    2011-11-30

    The program, entitled Development of Protective Coatings for Co-Sequestration Processes and Pipelines, examined the sensitivity of existing coating systems to supercritical carbon dioxide (SCCO2) exposure and developed new coating system to protect pipelines from their corrosion under SCCO2 exposure. A literature review was also conducted regarding pipeline corrosion sensors to monitor pipes used in handling co-sequestration fluids. Research was to ensure safety and reliability for a pipeline involving transport of SCCO2 from the power plant to the sequestration site to mitigate the greenhouse gas effect. Results showed that one commercial coating and one designed formulation can both be supplied as potential candidates for internal pipeline coating to transport SCCO2.

  16. SOUTHEAST REGIONAL CARBON SEQUESTRATION PARTNERSHP (SECARB)

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth J. Nemeth

    2005-04-01

    The Southeast Regional Carbon Sequestration Partnership (SECARB) is on schedule and within budget projections for the work completed during the first 18-months of its two year program. Work during the semiannual period (fifth and sixth project quarters) of the project (October 1, 2004-March 31, 2005) was conducted within a ''Task Responsibility Matrix.'' Under Task 1.0 Define Geographic Boundaries of the Region, no changes occurred during the fifth or sixth quarters of the project. Under Task 2.0 Characterize the Region, refinements have been made to the general mapping and screening of sources and sinks. Integration and geographical information systems (GIS) mapping is ongoing. Characterization during this period was focused on smaller areas having high sequestration potential. Under Task 3.0 Identify and Address Issues for Technology Deployment, SECARB continues to expand upon its assessment of safety, regulatory, permitting, and accounting frameworks within the region to allow for wide-scale deployment of promising terrestrial and geologic sequestration approaches. Under Task 4.0 Develop Public Involvement and Education Mechanisms, SECARB has used results of a survey and focus group meeting to refine approaches that are being taken to educate and involve the public. Under Task 5.0 Identify the Most Promising Capture, Sequestration, and Transport Options, SECARB has evaluated findings from work performed during the first 18-months. The focus of the project team has shifted from region-wide mapping and characterization to a more detailed screening approach designed to identify the most promising opportunities. Under Task 6.0 Prepare Action Plans for Implementation and Technology Validation Activity, the SECARB team is developing an integrated approach to implementing the most promising opportunities and in setting up measurement, monitoring and verification (MMV) programs for the most promising opportunities. Milestones completed during the

  17. Diagnosis of arterial sequestration using multidetector CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Yu Hong, E-mail: yuhong.2002@hotmail.com [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003 (China); Li Huimin, E-mail: lihuiminphd@163.com [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003 (China); Liu Shiyuan, E-mail: cjr.liushiyuan@vip.163.com [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003 (China); Xiao Xiangsheng, E-mail: cjr.xxsh@vip.163.com [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003 (China)

    2010-11-15

    Background: Arterial sequestration is a rare congenital disorder. The diagnostic evaluation of this condition using multidetector computerized tomography (MDCT) has not been described previously. The purpose of this study was to describe the characteristic features of this disorder and to assess the use of MDCT in visualizing the characteristic anatomic features. Methods: We retrospectively reviewed the records of seven patients with anomalous systemic blood supply to left lower lobe of the lung. All the patients had undergone MDCT angiography. To evaluate the lung parenchyma, bronchial branching pattern, and vascular anatomy, four series of images were systematically reconstructed as follows: contiguous transverse CT scans viewed at mediastinal and pulmonary window settings, oblique coronal and sagittal maximum intensity projections (MIP), multiplanar reconstruction (MPR), and three-dimensional volume-rendered images (VR) of airway and thoracic vascular structures. Results: All 7 cases had isolated and tortuous arterial anatomy from the descending thoracic aorta to the basal segment of the left lower lobe; however, variable distribution of branches was observed. Characteristic findings of anomalous systemic arterial (ASA) supply were distinct from those seen in other pulmonary sequestration syndromes and were well visualized by the use of noninvasive MDCT. Conclusion: Complex CT findings allow clear imaging of arterial sequestration and the ASA blood supply; MDCT angiography has demonstrated its value and accuracy in diagnosing this condition, obviating the use of digital subtraction angiography and magnetic resonance angiography for the diagnosis of arterial sequestration.

  18. Diagnosis of arterial sequestration using multidetector CT angiography

    International Nuclear Information System (INIS)

    Yu Hong; Li Huimin; Liu Shiyuan; Xiao Xiangsheng

    2010-01-01

    Background: Arterial sequestration is a rare congenital disorder. The diagnostic evaluation of this condition using multidetector computerized tomography (MDCT) has not been described previously. The purpose of this study was to describe the characteristic features of this disorder and to assess the use of MDCT in visualizing the characteristic anatomic features. Methods: We retrospectively reviewed the records of seven patients with anomalous systemic blood supply to left lower lobe of the lung. All the patients had undergone MDCT angiography. To evaluate the lung parenchyma, bronchial branching pattern, and vascular anatomy, four series of images were systematically reconstructed as follows: contiguous transverse CT scans viewed at mediastinal and pulmonary window settings, oblique coronal and sagittal maximum intensity projections (MIP), multiplanar reconstruction (MPR), and three-dimensional volume-rendered images (VR) of airway and thoracic vascular structures. Results: All 7 cases had isolated and tortuous arterial anatomy from the descending thoracic aorta to the basal segment of the left lower lobe; however, variable distribution of branches was observed. Characteristic findings of anomalous systemic arterial (ASA) supply were distinct from those seen in other pulmonary sequestration syndromes and were well visualized by the use of noninvasive MDCT. Conclusion: Complex CT findings allow clear imaging of arterial sequestration and the ASA blood supply; MDCT angiography has demonstrated its value and accuracy in diagnosing this condition, obviating the use of digital subtraction angiography and magnetic resonance angiography for the diagnosis of arterial sequestration.

  19. An equity assessment of introducing uncertain forest carbon sequestration in EU climate policy

    International Nuclear Information System (INIS)

    Münnich Vass, Miriam; Elofsson, Katarina; Gren, Ing-Marie

    2013-01-01

    Large emissions of greenhouse gases are expected to cause major environmental problems in the future. European policy makers have therefore declared that they aim to implement cost-efficient and fair policies to reduce carbon emissions. The purpose of this paper is to assess whether the cost of the EU policies for 2020 can be reduced through the inclusion of carbon sequestration as an abatement option while equity is also improved. The assessment is done by numerical calculations using a chance-constrained partial equilibrium model of the EU Emissions Trading Scheme and national effort-sharing targets, where forest sequestration is introduced as an uncertain abatement option. Fairness is evaluated by calculation of Gini-coefficients for six equity criteria to policy outcomes. The estimated Gini-coefficients range between 0.11 and 0.32 for the current policy, between 0.16 and 0.66 if sequestration is included and treated as certain, and between 0.19 and 0.38 when uncertainty about sequestration is taken into account and policy-makers wish to meet targets with at least 90 per cent probability. The results show that fairness is reduced when sequestration is included and that the impact is larger when sequestration is treated as certain. - Highlights: • We model EU's CO 2 emission reduction targets to 2020 for the 27 member states. • We assess the equity of including forest carbon sequestration in EU policy with six equity criteria. • A stochastic partial equilibrium model is used, in which abatement cost is minimised. • Current burden sharing within the EU is quite fair when compared with current income inequality. • The abatement cost is reduced and inequality increased when including sequestration

  20. Carbon dioxide (CO2) sequestration in deep saline aquifers and formations: Chapter 3

    Science.gov (United States)

    Rosenbauer, Robert J.; Thomas, Burt

    2010-01-01

    Carbon dioxide (CO2) capture and sequestration in geologic media is one among many emerging strategies to reduce atmospheric emissions of anthropogenic CO2. This chapter looks at the potential of deep saline aquifers – based on their capacity and close proximity to large point sources of CO2 – as repositories for the geologic sequestration of CO2. The petrochemical characteristics which impact on the suitability of saline aquifers for CO2 sequestration and the role of coupled geochemical transport models and numerical tools in evaluating site feasibility are also examined. The full-scale commercial CO2 sequestration project at Sleipner is described together with ongoing pilot and demonstration projects.

  1. Pulmonary sequestration: diagnosis with three dimensional reconstruction using spiral CT

    International Nuclear Information System (INIS)

    Nie Yongkang; Zhao Shaohong; Cai Zulong; Yang Li; Zhao Hong; Zhang Ailian; Huang Hui

    2003-01-01

    Objective: To evaluate the role of three dimensional (3D) reconstruction using spiral CT in the diagnosis of pulmonary sequestration. Methods: Ten patients with pulmonary sequestration were analyzed. The diagnoses were confirmed by angiography in 2 patients, by operation in 2 patients, and by CT angiography in 6 patients. All patients were examined with Philips SR 7000 or GE Lightspeed Plus scanner. CT images were transferred to a workstation and 3D reconstruction was performed. All images were reviewed and analyzed by two radiologists. Results: Among 10 patients, the pulmonary sequestration was in the right lower lobe in 1 patient and in the left lower lobe in 9 patients. Anomalous systemic arteries originated from thoracic aorta in 8 patients and from celiac artery in 2 patients. On plain CT scan, there were 4 patients with patchy opacities, 3 patients with hilar mass accompanying vascular engorgement and profusion in adjacent parenchyma, 2 patients with finger-like appendage surrounded by hyper-inflated lung, and 1 patient with lung mass-like lesion. Enhanced CT revealed anomalous systemic arteries in 9 patients and drainage vein in 7 patients. Maximum intensity projection (MIP) and curvilinear reconstruction could depict the abnormal systemic artery and drainage vein in sequestration. Surface shadow display (SSD) and volume rendering (VR) could delineate the anomalous systemic artery. Conclusion: 3D reconstruction with enhanced spiral CT can depict anomalous systemic artery and drainage vein and it is the first method of choice in diagnosing pulmonary sequestration

  2. AMP-Activated Protein Kinase Directly Phosphorylates and Destabilizes Hedgehog Pathway Transcription Factor GLI1 in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Yen-Hsing Li

    2015-07-01

    Full Text Available The Hedgehog (Hh pathway regulates cell differentiation and proliferation during development by controlling the Gli transcription factors. Cell fate decisions and progression toward organ and tissue maturity must be coordinated, and how an energy sensor regulates the Hh pathway is not clear. AMP-activated protein kinase (AMPK is an important sensor of energy stores and controls protein synthesis and other energy-intensive processes. AMPK is directly responsive to intracellular AMP levels, inhibiting a wide range of cell activities if ATP is low and AMP is high. Thus, AMPK can affect development by influencing protein synthesis and other processes needed for growth and differentiation. Activation of AMPK reduces GLI1 protein levels and stability, thus blocking Sonic-hedgehog-induced transcriptional activity. AMPK phosphorylates GLI1 at serines 102 and 408 and threonine 1074. Mutation of these three sites into alanine prevents phosphorylation by AMPK. This leads to increased GLI1 protein stability, transcriptional activity, and oncogenic potency.

  3. A General Methodology for Evaluation of Carbon Sequestration Activities and Carbon Credits

    Energy Technology Data Exchange (ETDEWEB)

    Klasson, KT

    2002-12-23

    A general methodology was developed for evaluation of carbon sequestration technologies. In this document, we provide a method that is quantitative, but is structured to give qualitative comparisons despite changes in detailed method parameters, i.e., it does not matter what ''grade'' a sequestration technology gets but a ''better'' technology should receive a better grade. To meet these objectives, we developed and elaborate on the following concepts: (1) All resources used in a sequestration activity should be reviewed by estimating the amount of greenhouse gas emissions for which they historically are responsible. We have done this by introducing a quantifier we term Full-Cycle Carbon Emissions, which is tied to the resource. (2) The future fate of sequestered carbon should be included in technology evaluations. We have addressed this by introducing a variable called Time-adjusted Value of Carbon Sequestration to weigh potential future releases of carbon, escaping the sequestered form. (3) The Figure of Merit of a sequestration technology should address the entire life-cycle of an activity. The figures of merit we have developed relate the investment made (carbon release during the construction phase) to the life-time sequestration capacity of the activity. To account for carbon flows that occur during different times of an activity we incorporate the Time Value of Carbon Flows. The methodology we have developed can be expanded to include financial, social, and long-term environmental aspects of a sequestration technology implementation. It does not rely on global atmospheric modeling efforts but is consistent with these efforts and could be combined with them.

  4. [Traumatic spondylolysis in the hedgehog. A contribution to the problem of isthmus dysplasia].

    Science.gov (United States)

    Roth, M

    1994-01-01

    Traumatic spondylolysis in a hedgehog is reported. On the basis of that rare observation the "dysplastic" thinning of the vertebral isthmus frequently associated with spondylolysis in man is claimed to be related to the "neuroenveloping" function of the spine shared with that of the neurocranium. Dysplasia of the isthmus results from abnormal ganglio-foraminal interrelation in the embryo rather than from any primary derangement of the vertebral bone growth proper.

  5. Analysis and Comparison of Carbon Capture & Sequestration Policies

    Science.gov (United States)

    Burton, E.; Ezzedine, S. M.; Reed, J.; Beyer, J. H.; Wagoner, J. L.

    2010-12-01

    Several states and countries have adopted or are in the process of crafting policies to enable geologic carbon sequestration projects. These efforts reflect the recognition that existing statutory and regulatory frameworks leave ambiguities or gaps that elevate project risk for private companies considering carbon sequestration projects, and/or are insufficient to address a government’s mandate to protect the public interest. We have compared the various approaches that United States’ state and federal governments have taken to provide regulatory frameworks to address carbon sequestration. A major purpose of our work is to inform the development of any future legislation in California, should it be deemed necessary to meet the goals of Assembly Bill 1925 (2006) to accelerate the adoption of cost-effective geologic sequestration strategies for the long-term management of industrial carbon dioxide in the state. Our analysis shows a diverse issues are covered by adopted and proposed carbon capture and sequestration (CCS) legislation and that many of the new laws focus on defining regulatory frameworks for underground injection of CO2, ambiguities in property issues, or assigning legal liability. While these approaches may enable the progress of early projects, future legislation requires a longer term and broader view that includes a quantified integration of CCS into a government’s overall climate change mitigation strategy while considering potentially counterproductive impacts on CCS of other climate change mitigation strategies. Furthermore, legislation should be crafted in the context of a vision for CCS as an economically viable and widespread industry. While an important function of new CCS legislation is enabling early projects, it must be kept in mind that applying the same laws or protocols in the future to a widespread CCS industry may result in business disincentives and compromise of the public interest in mitigating GHG emissions. Protection of the

  6. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

    International Nuclear Information System (INIS)

    Lin, Yi-Ting; Ding, Jing-Ya; Li, Ming-Yang; Yeh, Tien-Shun; Wang, Tsu-Wei; Yu, Jenn-Yah

    2012-01-01

    Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: ► YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. ► YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. ► Knockdown of Gli2 rescues the Yap-overexpression phenotype in P19 cells. ► Knockdown of Gli2 rescues the Yap

  7. YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yi-Ting; Ding, Jing-Ya [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Li, Ming-Yang [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yeh, Tien-Shun [Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Wang, Tsu-Wei [Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan (China); Yu, Jenn-Yah [Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Brain Research Center, National Yang-Ming University, Taipei 112, Taiwan (China)

    2012-09-10

    Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model to study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the Yap

  8. Making carbon dioxide sequestration feasible: Toward federal regulation of CO2 sequestration pipelines

    International Nuclear Information System (INIS)

    Mack, Joel; Endemann, Buck

    2010-01-01

    As the United States moves closer to a national climate change policy, it will have to focus on a variety of factors affecting the manner in which the country moves toward a future with a substantially lower carbon footprint. In addition to encouraging renewable energy, smart grid, clean fuels and other technologies, the United States will need to make substantial infrastructure investments in a variety of industries. Among the significant contributors to the current carbon footprint in the United States is the use of coal as a major fuel for the generation of electricity. One of the most important technologies that the United States can employ to reduce its carbon footprint is to sequester the carbon dioxide ('CO 2 ') from coal-fired power plants. This article focuses on the legal and policy issues surrounding a critical piece of the necessary sequestration infrastructure: CO 2 pipelines that will carry CO 2 from where it is removed from fuel or waste gas streams to where it will be sequestered. Ultimately, this article recommends developing a federally regulated CO 2 pipeline program to foster the implementation of carbon sequestration technology.

  9. Deep horizons: Soil Carbon sequestration and storage potential in grassland soils

    Science.gov (United States)

    Torres-Sallan, Gemma; Schulte, Rogier; Lanigan, Gary J.; Byrne, Kenneth A.; Reidy, Brian; Creamer, Rachel

    2016-04-01

    Soil Organic Carbon (SOC) enhances soil fertility, holding nutrients in a plant-available form. It also improves aeration and water infiltration. Soils are considered a vital pool for C (Carbon) sequestration, as they are the largest pool of C after the oceans, and contain 3.5 more C than the atmosphere. SOC models and inventories tend to focus on the top 30 cm of soils, only analysing total SOC values. Association of C with microaggregates (53-250 μm) and silt and clay (40 °C. Through a wet sieving procedure, four aggregate sizes were isolated: large macroaggregates (>2000 μm); macroaggregates (250-2000 μm); microaggregates and silt & clay. Organic C associated to each aggregate fraction was analysed on a LECO combustion analyser. Sand-free C was calculated for each aggregate size. For all soil types, 84% of the SOC located in the first 30 cm was contained inside macroaggregates and large macroaggregates. Given that this fraction has a turnover time of 1 to 10 years, sampling at that depth only provides information on the labile fraction in soil, and does not consider the longer term C sequestration potential. Only when looking at the whole profile, two clear trends could be observed: 1) soils with a clay increase at depth had most of their C located in the silt and clay fractions, which indicate their enhanced C sequestration capacity, 2) free-draining soils had a bigger part of their SOC located in the macroaggregate fractions. These results indicate that current C inventories and models that focus on the top 30 cm, do not accurately measure soil C sequestration potential in soils, but rather the more labile fraction. However, at depth soil forming processes have been identified as a major factor influencing C sequestration potential in soils. This has a major impact in further quantifying and sustaining C sequestration into the future. Soils with a high sequestration potential at depth need to be managed to enhance the residence time to contribute to future

  10. Pulmonary sequestrations of the upper lobe in children: Three presentations

    International Nuclear Information System (INIS)

    Hoeffel, J.C.; Bernard, C.; Didier, F.; Bretagne, M.C.; Gautry, P.; Olive, D.; Prevot, J.; Pernot, C.; Hopital des Enfants, 54 - Vandoeuvre-les-Nancy; Hopital des Enfants, 54 - Vandoeuvre-les-Nancy; Hopital des Enfants, 54 - Vandoeuvre-les-Nancy

    1986-01-01

    Pulmonary sequestrations are congenital abnormalities where nonfunctioning lung tissue receives its vascular supply from the systemic circulation (thoracic or abdominal aorta). It is necessary to establish the diagnosis in childhood when the lesions are uncomplicated. The authors present three cases of sequestration of the apex (2 extralobar and 1 atypical) with the main clinical and radiological features. Sequestrations in the upper lobe are rare, and the usual site is the left lower lobe. Plain X-rays show a dense opacity, sometimes with an air-fluid level: angiography is currently the best mean for definitive diagnosis; however, computed tomography will probably be very useful in the future. Differential diagnosis includes tumours of the superior mediastinum (neurogenic tumours, digestive duplication, bronchogenic cysts, pheochromocytoma and hydatid cysts). (orig.) [de

  11. Sequestration Options for the West Coast States

    Energy Technology Data Exchange (ETDEWEB)

    Myer, Larry

    2006-04-30

    The West Coast Regional Carbon Sequestration Partnership (WESTCARB) is one of seven partnerships that have been established by the U.S. Department of Energy (DOE) to evaluate carbon capture and sequestration (CCS) technologies best suited for different regions of the country. The West Coast Region comprises Arizona, California, Nevada, Oregon, Washington, Alaska, and British Columbia. Led by the California Energy Commission, WESTCARB is a consortium of about 70 organizations, including state natural resource and environmental protection agencies; national laboratories and universities; private companies working on carbon dioxide (CO{sub 2}) capture, transportation, and storage technologies; utilities; oil and gas companies; nonprofit organizations; and policy/governance coordinating organizations. Both terrestrial and geologic sequestration options were evaluated in the Region during the 18-month Phase I project. A centralized Geographic Information System (GIS) database of stationary source, geologic and terrestrial sink data was developed. The GIS layer of source locations was attributed with CO{sub 2} emissions and other data and a spreadsheet was developed to estimate capture costs for the sources in the region. Phase I characterization of regional geological sinks shows that geologic storage opportunities exist in the WESTCARB region in each of the major technology areas: saline formations, oil and gas reservoirs, and coal beds. California offers outstanding sequestration opportunities because of its large capacity and the potential of value-added benefits from enhanced oil recovery (EOR) and enhanced gas recovery. The estimate for storage capacity of saline formations in the ten largest basins in California ranges from about 150 to about 500 Gt of CO{sub 2}, the potential CO{sub 2}-EOR storage was estimated to be 3.4 Gt, and the cumulative production from gas reservoirs suggests a CO{sub 2} storage capacity of 1.7 Gt. A GIS-based method for source

  12. Congenital erythropoietic porphyria in an African hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Wolff, Carlos; Corradini, Paulina; Cortés, Galaxia

    2005-06-01

    A 6-mo-old, male African hedgehog (Atelerix albiventris) presented with a history of pink urine and demonstrating pink-colored teeth and mild hepatomegaly on examination. Urinalysis revealed no physical, chemical, or cellular abnormalities other than a pink color and fluorescence under ultraviolet light (UV). Also under UV, intense fluorescence of teeth, feet, and spines was noted. Porphyria was suspected. Spectrophotometric evaluation of urine showed extremely elevated levels of copro- and uroporphyrins. Analysis of the urine by thin-layer chromatography showed an abnormal pattern of excreted porphyrin intermediates. Urine high-performance thin-layer chromatography showed that excreted porphyrins were 90-95% of the type-I isomeric form, suggestive of congenital erythropoietic porphyria.

  13. Defect-Induced Hedgehog Polarization States in Multiferroics

    Science.gov (United States)

    Li, Linze; Cheng, Xiaoxing; Jokisaari, Jacob R.; Gao, Peng; Britson, Jason; Adamo, Carolina; Heikes, Colin; Schlom, Darrell G.; Chen, Long-Qing; Pan, Xiaoqing

    2018-03-01

    Continuous developments in nanotechnology require new approaches to materials synthesis that can produce novel functional structures. Here, we show that nanoscale defects, such as nonstoichiometric nanoregions (NSNRs), can act as nano-building blocks for creating complex electrical polarization structures in the prototypical multiferroic BiFeO3 . An array of charged NSNRs are produced in BiFeO3 thin films by tuning the substrate temperature during film growth. Atomic-scale scanning transmission electron microscopy imaging reveals exotic polarization rotation patterns around these NSNRs. These polarization patterns resemble hedgehog or vortex topologies and can cause local changes in lattice symmetries leading to mixed-phase structures resembling the morphotropic phase boundary with high piezoelectricity. Phase-field simulations indicate that the observed polarization configurations are mainly induced by charged states at the NSNRs. Engineering defects thus may provide a new route for developing ferroelectric- or multiferroic-based nanodevices.

  14. CO2 sequestration using principles of shell formation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Woo; Jang, Young-Nam [CO2 Sequestration Research Department, Korea Institute of Geoscience and Mineral Resources (Korea, Republic of); Lee, Si-Hyun; Lim, Kyoung-Soo; Jeong, Soon-Kwan [Energy Conservation Research Department of Clean Energy System Research Center, Korea Institute of Energy Research (Korea, Republic of)

    2011-06-15

    The biomimetic sequestration of carbon dioxide to reduce the CO2 emitted into the atmosphere is introduced in this paper. Bivalve shells are used as a good model of CO2 sequestration in this paper, because the shell is derived from the calcium ions and CO2 in seawater. Carbonic anhydrase, hemocyte from diseased shell (HDS) and extrapallial fluid (EFP) are involved in shell formation. This paper compares the soluble protein extracted from Crassostrea gigas with bovine carbonic anhydrase II in terms of their ability to promote CO2 hydration and the production of calcium precipitates. The result demonstrates that HDS has more functional groups to bind calcium ions in aqueous systems, and a different process of calcium precipitation, than does bovine carbonic anhydrase II. To understand molecular weight and secondary protein structure, mass-spectroscopic analysis (MALDI-TOF) and circular dichroism (CD) analysis were used. With regard to EPF, EPF related to shell formation is composed of several fractions and plays a role in sequestration of CO2.

  15. Terrestrial Carbon Sequestration: Analysis of Terrestrial Carbon Sequestration at Three Contaminated Sites Remediated and Revitalized with Soil Amendments

    Science.gov (United States)

    This paper provides EPA's analysis of the data to determine carbon sequestration rates at three diverse sites that differ in geography/location, weather, soil properties, type of contamination, and age.

  16. Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

    Science.gov (United States)

    Chandra, Vikas; Das, Tapojyoti; Gulati, Puneet; Biswas, Nidhan K; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N; Deb, Sumit; Saha, Suniti K; Chowdhury, Anup K; Ghosh, Subhashish; Rudin, Charles M; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution-unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh" cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

  17. Comparison of carbon sequestration potential in agricultural and afforestation farming systems

    Directory of Open Access Journals (Sweden)

    Chinsu Lin

    2013-04-01

    Full Text Available In the last few decades, many forests have been cut down to make room for cultivation and to increase food or energy crops production in developing countries. In this study, carbon sequestration and wood production were evaluated on afforested farms by integrating the Gaussian diameter distribution model and exponential diameter-height model derived from sample plots of an afforested hardwood forest in Taiwan. The quantity of sequestrated carbon was determined based on aboveground biomass. Through pilot tests run on an age-volume model, an estimation bias was obtained and used to correct predicted volume estimates for a farm forest over a 20-year period. An estimated carbon sequestration of 11,254 t C was observed for a 189ha-hardwood forest which is equivalent to 41,264 t CO2. If this amount of carbon dioxide were exchanged on the Chicago Climate Exchange (CCX market, the income earned would be 821 US$ ha- 1. Carbon sequestration from rice (Oryza sativa or sugarcane (Saccharum officinarum production is discharged as a result of straw decomposition in the soil which also improves soil quality. Sugarcane production does not contribute significantly to carbon sequestration, because almost all the cane fiber is used as fuel for sugar mills. As a result of changing the farming systems to hardwood forest in this study area, carbon sequestration and carbon storage have increased at the rate of 2.98 t C ha- 1 year- 1. Net present value of afforestation for a 20-year period of carbon or wood management is estimated at around US$ 30,000 given an annual base interest rate of 3 %.

  18. 75 FR 75059 - Mandatory Reporting of Greenhouse Gases: Injection and Geologic Sequestration of Carbon Dioxide

    Science.gov (United States)

    2010-12-01

    ... Greenhouse Gases: Injection and Geologic Sequestration of Carbon Dioxide; Final Rule #0;#0;Federal Register... Mandatory Reporting of Greenhouse Gases: Injection and Geologic Sequestration of Carbon Dioxide AGENCY... greenhouse gas monitoring and reporting from facilities that conduct geologic sequestration of carbon dioxide...

  19. Going With the Flow: An Aid in Detecting and Differentiating Bronchopulmonary Sequestrations and Hybrid Lesions.

    Science.gov (United States)

    Oliver, Edward R; DeBari, Suzanne E; Giannone, Mariann M; Pogoriler, Jennifer E; Johnson, Ann M; Horii, Steven C; Gebb, Juliana S; Howell, Lori J; Adzick, N Scott; Coleman, Beverly G

    2018-02-01

    To assess the ability of prenatal ultrasound (US) in identifying systemic feeding arteries in bronchopulmonary sequestrations and hybrid lesions and report the ability of US in classifying bronchopulmonary sequestrations as intralobar or extralobar. Institutional Review Board-approved radiology and clinical database searches from 2008 to 2015 were performed for prenatal lung lesions with final diagnoses of bronchopulmonary sequestrations or hybrid lesions. All patients had detailed US examinations, and most patients had ultrafast magnetic resonance imaging (MRI). Lesion location, size, and identification of systemic feeding arteries and draining veins were assessed with US. The study consisted of 102 bronchopulmonary sequestrations and 86 hybrid lesions. The median maternal age was 30 years. The median gestational age was 22 weeks 5 days. Of bronchopulmonary sequestrations, 66 had surgical pathologic confirmation, and 100 had postnatal imaging. Bronchopulmonary sequestration locations were intrathoracic (n = 77), intra-abdominal (n = 19), and transdiaphragmatic (n = 6). Of hybrid lesions, 84 had surgical pathologic confirmation, and 83 had postnatal imaging. Hybrid lesion locations were intrathoracic (n = 84) and transdiaphragmatic (n = 2). Ultrasound correctly identified systemic feeding arteries in 86 of 102 bronchopulmonary sequestrations and 79 of 86 hybrid lesions. Of patients who underwent MRI, systemic feeding arteries were reported in 62 of 92 bronchopulmonary sequestrations and 56 of 81 hybrid lesions. Ultrasound identified more systemic feeding arteries than MRI in both bronchopulmonary sequestrations and hybrid lesions (P < .01). Magnetic resonance imaging identified systemic feeding arteries that US did not in only 2 cases. In cases in which both systemic feeding arteries and draining veins were identified, US could correctly predict intrathoracic lesions as intralobar or extralobar in 44 of 49 bronchopulmonary sequestrations and

  20. INSURER SEQUESTRATION OF THE DEBTOR’S IMMOVABLE PROPERTY IN BUSINESS

    Directory of Open Access Journals (Sweden)

    NICOLAE GRADINARU

    2011-04-01

    Full Text Available Insurer sequestration is the insurance measure that the creditor resorts to and that is applicable if the object of the litigation is the payment of a sum of money and that consists of the unavailability of the debtor-defendant’s sequestrable movable or immovable property, until the final (irrevocable decision given in the main trial in order to profit from the property when the creditor will obtain a writ of execution. In this regard, there are the provisions of Article 591 paragraph 1 thesis I of the Civil Procedure Code: “A creditor who does not have the writ of execution, but whose claim is proven by written act and is exigible, may request the setting up of an insurer sequestration of the debtor’s movable and immovable property, if he proves that he took legal action”. Thus, the provisions of article 907 are understood by reference to the provisions of article 591 paragraph 1 thesis I art.591 of the Civil Procedure Code, in that: in business, the insurer sequestration may also be set up on the debtor’s immovable property.

  1. Intralobar bronchopulmonary sequestration: A case and brief review

    Directory of Open Access Journals (Sweden)

    Majumdar U

    2018-06-01

    Full Text Available Objective: Bronchopulmonary sequestration is a rare congenital abnormality of the lower respiratory tract, seen mostly in children but often in adults. The term implies a mass of lung tissue that has no function and lacks normal communication with the rest of the tracheobronchial tree. Case: A 40-year-old man presented with acute onset of left flank pain for 4 hours. He was born in Yemen and emigrated to the US in 1998; at that time, he had been tested for tuberculosis which was negative. In this admission, he met systemic inflammatory response (SIRS criteria and had basilar crackles in the left lower lobe of the lung. CT scan revealed a cavitary lesion with air-fluid level in the left lower lobe airspace. There was systemic arterial blood supply to this region arising off the celiac axis. He was diagnosed with an infected intralobar bronchopulmonary sequestration and underwent video-assisted thoracoscopic wedge resection. On follow up 3 months later, he was doing well. Discussion: Pulmonary sequestration is a rare congenital anomaly of a mass of lung tissue, which can have cystic changes and is a very important differential diagnosis of cavities in the lung. Confirmation of diagnosis is by visualization of a systemic vessel supplying sequestrated pulmonary, and this is accomplished by contrast-enhanced CT scan, MRI or invasive angiography. Conclusion: The delay in diagnosis in our patient was due to falling prey to anchoring and availability biases and chasing the diagnosis of tuberculosis in a patient from Yemen with a lower lobe cavitation.

  2. INTERNATIONAL COLLABORATION ON CO2 SEQUESTRATION

    Energy Technology Data Exchange (ETDEWEB)

    H.J. Herzog; E.E. Adams

    2000-08-23

    The specific objective of our project on CO{sub 2} ocean sequestration is to investigate its technical feasibility and to improve the understanding of any associated environmental impacts. Our ultimate goal is to minimize any impacts associated with the eventual use of ocean carbon sequestration to reduce greenhouse gas concentrations in the atmosphere. The project will continue through March 31, 2002, with a field experiment to take place in the summer of 2001 off the Kona Coast of Hawaii. At GHGT-4 in Interlaken, we presented a paper detailing our plans. The purpose of this paper is to present an update on our progress to date and our plans to complete the project. The co-authors of this paper are members of the project's Technical Committee, which has been formed to supervise the technical aspects and execution of this project.

  3. Soil carbon sequestration and biochar as negative emission technologies.

    Science.gov (United States)

    Smith, Pete

    2016-03-01

    Despite 20 years of effort to curb emissions, greenhouse gas (GHG) emissions grew faster during the 2000s than in the 1990s, which presents a major challenge for meeting the international goal of limiting warming to deforestation, showed that all NETs have significant limits to implementation, including economic cost, energy requirements, land use, and water use. In this paper, I assess the potential for negative emissions from soil carbon sequestration and biochar addition to land, and also the potential global impacts on land use, water, nutrients, albedo, energy and cost. Results indicate that soil carbon sequestration and biochar have useful negative emission potential (each 0.7 GtCeq. yr(-1) ) and that they potentially have lower impact on land, water use, nutrients, albedo, energy requirement and cost, so have fewer disadvantages than many NETs. Limitations of soil carbon sequestration as a NET centre around issues of sink saturation and reversibility. Biochar could be implemented in combination with bioenergy with carbon capture and storage. Current integrated assessment models do not represent soil carbon sequestration or biochar. Given the negative emission potential of SCS and biochar and their potential advantages compared to other NETs, efforts should be made to include these options within IAMs, so that their potential can be explored further in comparison with other NETs for climate stabilization. © 2016 John Wiley & Sons Ltd.

  4. ESTIMATION OF CARBON SEQUESTRATION BY RUSSIAN FORESTS: GEOSPATIAL ISSUE

    Directory of Open Access Journals (Sweden)

    N. V. Malysheva

    2017-01-01

    Full Text Available Сategories of carbon sequestration assessment for Russian forests are identified by GIS toolkit. Those are uniform by bioclimatic and site-specific conditions strata corresponding to modern version of bioclimatic forest district division. Stratification of forests at early stage substantially reduces the ambiguity of the evaluation because phytomass conversion sequestration capacity and expansion factor dependent on site-specific condition for calculating of forest carbon sink are absolutely necessary. Forest management units were linked to strata. Biomass conversion and expansion factor for forest carbon sink assessment linked to the strata were recalculated for forest management units. All operations were carried out with GIS analytical toolkit due to accessible functionalities. Units for forest carbon storage inventory and forest carbon balance calculation were localized. Production capacity parameters and forest carbon sequestration capacity have been visualized on maps complied by ArcGIS. Based on spatially-explicit information, we have found out that the greatest annual rates of forest’s carbon accumulation in Russian forests fall into mixed coniferous-deciduous forests of European-Ural part of Russia to Kaliningrad, Smolensk and Briansk Regions, coniferous-deciduous forests close to the boundary of Khabarovsk Region and Primorskij Kray in the Far East, as well as separate forest management units of Kabardino-Balkariya NorthCaucasian mountain area. The geospatial visualization of carbon sequestration by Russian forests and carbon balance assessment has been given.

  5. CRADA Carbon Sequestration in Soils and Commercial Products

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.K.

    2002-01-31

    ORNL, through The Consortium for Research on Enhancing Carbon Sequestration in Terrestrial Ecosystems (CSiTE), collaborated with The Village Botanica, Inc. (VB) on a project investigating carbon sequestration in soils and commercial products from a new sustainable crop developed from perennial Hibiscus spp. Over 500 pre-treated samples were analyzed for soil carbon content. ORNL helped design a sampling scheme for soils during the planting phase of the project. Samples were collected and prepared by VB and analyzed for carbon content by ORNL. The project did not progress to a Phase II proposal because VB declined to prepare the required proposal.

  6. Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling

    OpenAIRE

    Murtaugh, L. Charles; Chyung, Jay H.; Lassar, Andrew B.

    1999-01-01

    Previous work has indicated that signals from the floor plate and notochord promote chondrogenesis of the somitic mesoderm. These tissues, acting through the secreted signaling molecule Sonic hedgehog (Shh), appear to be critical for the formation of the sclerotome. Later steps in the differentiation of sclerotome into cartilage may be independent of the influence of these axial tissues. Although the signals involved in these later steps have not yet been pinpointed, there is substantial evid...

  7. Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.

    Science.gov (United States)

    Ross, Ashley E; Hughes, Robert M; Glavaris, Stephanie; Ghabili, Kamyar; He, Ping; Anders, Nicole M; Harb, Rana; Tosoian, Jeffrey J; Marchionni, Luigi; Schaeffer, Edward M; Partin, Alan W; Allaf, Mohamad E; Bivalacqua, Trinity J; Chapman, Carolyn; O'Neal, Tanya; DeMarzo, Angelo M; Hurley, Paula J; Rudek, Michelle A; Antonarakis, Emmanuel S

    2017-11-28

    To determine the pharmacodynamic effects of Sonidegib (LDE-225) in prostate tumor tissue from men with high-risk localized prostate cancer, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy. We conducted a prospective randomized (Sonidegib vs. observation) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy. The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue. Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy, and safety. Fourteen men were equally randomized (7 per arm) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy. Six of seven men (86%) in the Sonidegib arm (and none in the control group) achieved a GLI1 suppression of at least two-fold. In the Sonidegib arm, drug was detectable in plasma and in prostatic tissue; and median intra-patient GLI1 expression decreased by 63-fold, indicating potent suppression of Hedgehog signaling. Sonidegib was well tolerated, without any Grade 3-4 adverse events observed. Disease-free survival was comparable among the two arms (HR = 1.50, 95% CI 0.26-8.69, P = 0.65). Hedgehog pathway activity (as measured by GLI1 expression) was detectable at baseline in men with localized high-risk prostate cancer. Sonidegib penetrated into prostatic tissue and induced a >60-fold suppression of the Hedgehog pathway. The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear.

  8. Land-use change and carbon sinks: Econometric estimation of the carbon sequestration supply function

    Energy Technology Data Exchange (ETDEWEB)

    Lubowski, Ruben N.; Plantinga, Andrew J.; Stavins, Robert N.

    2001-01-01

    Increased attention by policy makers to the threat of global climate change has brought with it considerable interest in the possibility of encouraging the expansion of forest area as a means of sequestering carbon dioxide. The marginal costs of carbon sequestration or, equivalently, the carbon sequestration supply function will determine the ultimate effects and desirability of policies aimed at enhancing carbon uptake. In particular, marginal sequestration costs are the critical statistic for identifying a cost-effective policy mix to mitigate net carbon dioxide emissions. We develop a framework for conducting an econometric analysis of land use for the forty-eight contiguous United States and employing it to estimate the carbon sequestration supply function. By estimating the opportunity costs of land on the basis of econometric evidence of landowners' actual behavior, we aim to circumvent many of the shortcomings of previous sequestration cost assessments. By conducting the first nationwide econometric estimation of sequestration costs, endogenizing prices for land-based commodities, and estimating land-use transition probabilities in a framework that explicitly considers the range of land-use alternatives, we hope to provide better estimates eventually of the true costs of large-scale carbon sequestration efforts. In this way, we seek to add to understanding of the costs and potential of this strategy for addressing the threat of global climate change.

  9. Carbon sequestration in the agroecosystem

    Directory of Open Access Journals (Sweden)

    Tomáš Středa

    2008-01-01

    Full Text Available Reduction of amount CO2 is possible by carbon sequestration to the soil. Fixation potential of EU–15 agricultural land is c. 16–19 mil t C . year−1. Amount and composition of post–harvest residues is essential for carbon soil sequestration. Long–term yield series of the most planted crops (winter wheat – Triticum aestivum, spring barley – Hordeum vulgare, corn and silage maize – Zea mays, winter rape – Brassica napus, potatoes – Solanum tuberosum, sugar beet – Beta vulgaris, alfalfa – Medicago sativa, red clover – Trifolium pratense, white mustard – Sinapis alba and fiddleneck – Phacelia tanacetifolia in various agroecological conditions and growing technologies were used for carbon balance calculation. The carbon balances were calculated for main crop rotations of maize, sugar beet, cereal and potato production regions (24 crop rotations. The calculations were realized for following planting varieties: traditional, commercial, ecological and with higher rate of winter rape. All chosen crop rotations (except seven have positive carbon balance in the tillage system. Amount of fixed carbon might be increases about 30% by the use of no–tillage system. Least amount of carbon is fixed by potatoes, high amount by cereals, alfalfa and sugar beet. For a short time (months the crops sequestration of carbon is relatively high (to 4.4 t . ha−1 . year−1 or to 5.7 t . ha−1 . year−1 for no–tillage system. From the long time viewpoint (tens of years the data of humified carbon in arable soil (max 400 kg C . ha−1 . year−1 are important. Maximal carbon deficit of chosen crop rotation is 725 kg C . year−1.

  10. Biochar production for carbon sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Thakkar, J.; Kumar, A. [Alberta Univ., Edmonton, AB (Canada). Dept. of Mechanical Engineering

    2010-07-01

    This study examined the use of agricultural biomass for biochar production and its storage in a landfill to sequester carbon. Capturing the energy from biomass that would otherwise decay, is among the many options available to mitigate the impact of the greenhouse gas (GHG) emissions associated with fossil fuel consumption. Biochar is a solid fuel which can be produced from agricultural biomass such as wheat and barley straw. This organic solid can be produced by slow pyrolysis of straw. A conceptual techno-economic model based on actual data was used to estimate the cost of producing biochar from straw in a centralized plant. The objectives of the study were to estimate the overall delivered cost of straw to the charcoal production plant; estimate the transportation costs of charcoal to the landfill site; estimate the cost of landfill; and estimate the overall cost of carbon sequestration through a charcoal landfill. According to preliminary results, the cost of carbon sequestration through this pathway is greater than $50 per tonne of carbon dioxide.

  11. Correlation Between Hedgehog (Hh) Protein Family and Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder (ASD).

    Science.gov (United States)

    Halepoto, Dost Muhammad; Bashir, Shahid; Zeina, Rana; Al-Ayadhi, Laila Y

    2015-12-01

    To determine the correlation of Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Brain-Derived Neurotrophic Factor (BDNF) in children with Autism Spectrum Disorder (ASD). An observational, comparative study. Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2011 to May 2012. Serum levels of SHH, IHH and BDNF were determined in recently diagnosed autistic patients and age-matched healthy children (n=25), using the Enzyme-Linked Immunosorbent Assay (ELISA). Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. Spearman correlation co-efficient 'r' was determined. The serum levels of IHH and SHH were significantly higher in autistic subjects than those of control subjects. There was significant correlation between age and IHH (r = 0.176, p = 0.03), BDNF and severe IHH (r = 0.1763, p = 0.003), and severe BDNF and severe SHH (r = 0.143, p autism.

  12. Sonic hedgehog protein promotes proliferation and chondrogenic differentiation of bone marrow-derived mesenchymal stem cells in vitro.

    Science.gov (United States)

    Warzecha, Jörg; Göttig, Stephan; Brüning, Christian; Lindhorst, Elmar; Arabmothlagh, Mohammad; Kurth, Andreas

    2006-10-01

    Sonic hedgehog (Shh) protein is known to be an important signaling protein in early embryonic development. Also, Shh is involved in the induction of early cartilaginous differentiation of mesenchymal cells in the limb and in the spine. The impact of Shh on adult stem cells, human bone marrow-derived mesenchymal stem cells (MSCs), was tested. The MSCs were treated either with recombinant Sonic hedgehog protein (r-Shh) or with transforming growth factor-beta 1 (TGF-beta(1)) as a positive control in vitro for 3 weeks. The effects on cartilaginous differentiation and proliferation were assayed. MSCs when treated with either Shh or TGF-beta(1) showed expression of cartilage markers aggrecan, Sox9, CEP-68, and collagen type II and X within 3 weeks. Only r-Shh-treated cells showed a very strong cell proliferation and much higher BrdU incorporation in cell assay systems. These are the first data that indicate an important role of Shh for the induction of cartilage production by MSCs in vitro.

  13. Synthesis and characterisation of 5-acyl-6,7-dihydrothieno[3,2-c]pyridine inhibitors of Hedgehog acyltransferase

    Directory of Open Access Journals (Sweden)

    Thomas Lanyon-Hogg

    2016-06-01

    Full Text Available In this data article we describe synthetic and characterisation data for four members of the 5-acyl-6,7-dihydrothieno[3,2-c]pyridine (termed “RU-SKI” class of inhibitors of Hedgehog acyltransferase, including associated NMR spectra for final compounds. RU-SKI compounds were selected for synthesis based on their published high potencies against the enzyme target. RU-SKI 41 (9a, RU-SKI 43 (9b, RU-SKI 101 (9c, and RU-SKI 201 (9d were profiled for activity in the related article “Click chemistry armed enzyme linked immunosorbent assay to measure palmitoylation by Hedgehog acyltransferase” (Lanyon-Hogg et al., 2015 [1]. 1H NMR spectral data indicate different amide conformational ratios between the RU-SKI inhibitors, as has been observed in other 5-acyl-6,7-dihydrothieno[3,2-c]pyridines. The synthetic and characterisation data supplied in the current article provide validated access to the class of RU-SKI inhibitors.

  14. Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

    Science.gov (United States)

    Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W.; Trudeau, Louis-Eric

    2014-01-01

    Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. PMID:24022593

  15. Characterization of Most Promising Sequestration Formations in the Rocky Mountain Region (RMCCS)

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Brian; Matthews, Vince

    2013-09-30

    The primary objective of the “Characterization of Most Promising Carbon Capture and Sequestration Formations in the Central Rocky Mountain Region” project, or RMCCS project, is to characterize the storage potential of the most promising geologic sequestration formations within the southwestern U.S. and the Central Rocky Mountain region in particular. The approach included an analysis of geologic sequestration formations under the Craig Power Station in northwestern Colorado, and application or extrapolation of those local-scale results to the broader region. A ten-step protocol for geologic carbon storage site characterization was a primary outcome of this project.

  16. Sequestration of organochlorine pesticides in soils of distinct organic carbon content

    International Nuclear Information System (INIS)

    Zhang Na; Yang Yu; Tao Shu; Liu Yan; Shi Kelu

    2011-01-01

    In the present study, five soil samples with organic carbon contents ranging from 0.23% to 7.1% and aged with technical dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) for 15 months were incubated in a sealed chamber to investigate the dynamic changes of the OCP residues. The residues in the soils decreased over the incubation period and finally reached a plateau. Regression analysis showed that degradable fractions of OCPs were negatively correlated with soil organic carbon (SOC) except for α-HCH, while no correlation was found between degradation rate and SOC, which demonstrated that SOC content determines the OCP sequestration fraction in soil. Analysis of the ratio of DDT and its primary metabolites showed that, since it depends on differential sequestration among them, magnitude of (p,p'-DDE + p,p'-DDD)/p,p'-DDT is not a reliable criterion for the identification of new DDT sources. - Research highlights: → Soil organic carbon content determines the OCP sequestration fraction in soil. → Magnitude of (p,p'-DDE + p,p'-DDD)/p,p'-DDT is not a reliable criterion for the identification of new DDT sources. → The more hydrophobic compounds have relatively higher sequestration fractions in soils with SOC contents >2%. → DDD may have higher sorption by soil organic matter than DDE. - The effect of soil organic matter on the sequestration of organochlorine pesticides (HCHs and DDTs) in soils was investigated in an innovative microcosm chamber.

  17. Aerobic, Metal-Free, and Catalytic Dehydrogenative Coupling of Heterocycles: En Route to Hedgehog Signaling Pathway Inhibitors.

    Science.gov (United States)

    Bering, Luis; Paulussen, Felix M; Antonchick, Andrey P

    2018-04-06

    The nitrosonium ion-catalyzed dehydrogenative coupling of heteroarenes under mild reaction conditions is reported. The developed method utilizes ambient molecular oxygen as a terminal oxidant, and only water is produced as byproduct. Dehydrogenative coupling of heteroarenes translated into the rapid discovery of novel hedgehog signaling pathway inhibitors, emphasizing the importance of the developed methodology.

  18. Carbon dioxide sequestration by mineral carbonation

    NARCIS (Netherlands)

    Huijgen, W.J.J.

    2007-01-01

    The increasing atmospheric carbon dioxide (CO2) concentration, mainly caused by fossil fuel combustion, has lead to concerns about global warming. A possible technology that can contribute to the reduction of carbon dioxide emissions is CO2 sequestration by mineral carbonation. The basic concept

  19. Generalized hedgehog ansatz and Gribov copies in regions with nontrivial topologies

    Science.gov (United States)

    Canfora, Fabrizio; Salgado-Rebolledo, Patricio

    2013-02-01

    In this paper the arising of Gribov copies both in Landau and Coulomb gauges in regions with nontrivial topologies but flat metric, (such as closed tubes S1×D2, or R×T2) will be analyzed. Using a novel generalization of the hedgehog ansatz beyond spherical symmetry, analytic examples of Gribov copies of the vacuum will be constructed. Using such ansatz, we will also construct the elliptic Gribov pendulum. The requirement of absence of Gribov copies of the vacuum satisfying the strong boundary conditions implies geometrical constraints on the shapes and sizes of the regions with nontrivial topologies.

  20. Near-term deployment of carbon capture and sequestration from biorefineries in the United States.

    Science.gov (United States)

    Sanchez, Daniel L; Johnson, Nils; McCoy, Sean T; Turner, Peter A; Mach, Katharine J

    2018-05-08

    Capture and permanent geologic sequestration of biogenic CO 2 emissions may provide critical flexibility in ambitious climate change mitigation. However, most bioenergy with carbon capture and sequestration (BECCS) technologies are technically immature or commercially unavailable. Here, we evaluate low-cost, commercially ready CO 2 capture opportunities for existing ethanol biorefineries in the United States. The analysis combines process engineering, spatial optimization, and lifecycle assessment to consider the technical, economic, and institutional feasibility of near-term carbon capture and sequestration (CCS). Our modeling framework evaluates least cost source-sink relationships and aggregation opportunities for pipeline transport, which can cost-effectively transport small CO 2 volumes to suitable sequestration sites; 216 existing US biorefineries emit 45 Mt CO 2 annually from fermentation, of which 60% could be captured and compressed for pipeline transport for under $25/tCO 2 A sequestration credit, analogous to existing CCS tax credits, of $60/tCO 2 could incent 30 Mt of sequestration and 6,900 km of pipeline infrastructure across the United States. Similarly, a carbon abatement credit, analogous to existing tradeable CO 2 credits, of $90/tCO 2 can incent 38 Mt of abatement. Aggregation of CO 2 sources enables cost-effective long-distance pipeline transport to distant sequestration sites. Financial incentives under the low-carbon fuel standard in California and recent revisions to existing federal tax credits suggest a substantial near-term opportunity to permanently sequester biogenic CO 2 This financial opportunity could catalyze the growth of carbon capture, transport, and sequestration; improve the lifecycle impacts of conventional biofuels; support development of carbon-negative fuels; and help fulfill the mandates of low-carbon fuel policies across the United States. Copyright © 2018 the Author(s). Published by PNAS.

  1. CO2 emissions abatement and geologic sequestration - industrial innovations and stakes - status of researches in progress

    International Nuclear Information System (INIS)

    2005-01-01

    This colloquium was jointly organized by the French institute of petroleum (IFP), the French agency of environmental and energy mastery (Ademe) and the geological and mining research office (BRGM). This press kit makes a status of the advances made in CO 2 emissions abatement and geological sequestration: technological advances of CO 2 capture and sequestration, geological reservoir dimensioning with respect to the problem scale, duration of such an interim solution, CO 2 emissions abatement potentialities of geological sequestration, regulatory, economical and financial implications, international stakes of greenhouse gas emissions. This press kit comprises a press release about the IFP-Ademe-BRGM colloquium, a slide presentation about CO 2 abatement and sequestration, and four papers: a joint IFP-Ademe-BRGM press conference, IFP's answers to CO 2 emissions abatement, Ademe's actions in CO 2 abatement and sequestration, and BRGM's experience in CO 2 sequestration and climatic change expertise. (J.S.)

  2. [Estimation of soil carbon sequestration potential in typical steppe of Inner Mongolia and associated uncertainty].

    Science.gov (United States)

    Wang, Wei; Wu, Jian-Guo; Han, Xing-Guo

    2012-01-01

    Based on the measurements in the enclosure and uncontrolled grazing plots in the typical steppe of Xilinguole, Inner Mongolia, this paper studied the soil carbon storage and carbon sequestration in the grasslands dominated by Leymus chinensis, Stipa grandis, and Stipa krylovii, respectively, and estimated the regional scale soil carbon sequestration potential in the heavily degraded grassland after restoration. At local scale, the annual soil carbon sequestration in the three grasslands all decreased with increasing year of enclosure. The soil organic carbon storage was significantly higher in the grasslands dominated by L. chinensis and Stipa grandis than in that dominated by Stipa krylovii, but the latter had much higher soil carbon sequestration potential, because of the greater loss of soil organic carbon during the degradation process due to overgrazing. At regional scale, the soil carbon sequestration potential at the depth of 0-20 cm varied from -0.03 x 10(4) to 3.71 x 10(4) kg C x a(-1), and the total carbon sequestration potential was 12.1 x 10(8) kg C x a(-1). Uncertainty analysis indicated that soil gravel content had less effect on the estimated carbon sequestration potential, but the estimation errors resulted from the spatial interpolation of climate data could be about +/- 4.7 x 10(9) kg C x a(-1). In the future, if the growth season precipitation in this region had an average variation of -3.2 mm x (10 a)(-1), the soil carbon sequestration potential would be de- creased by 1.07 x 10(8) kg C x (10 a)(-1).

  3. CARBON SEQUESTRATION AND PLANT COMMUNITY DYNAMICS FOLLOWING REFORESTATION OF TROPICAL PASTURE.

    Science.gov (United States)

    WHENDEE L. SILVER; LARA M. KUEPPERS; ARIEL E. LUGO; REBECCA OSTERTAG; VIRGINIA MATZEK

    2004-01-01

    Conversion of abandoned cattle pastures to secondary forests and plantations in the tropics has been proposed as a means to increase rates of carbon (C) sequestration from the atmosphere and enhance local biodiversity. We used a long-term tropical reforestation project (55–61 yr) to estimate rates of above- and belowground C sequestration and to investigate the impact...

  4. Reduced carbon sequestration potential of biochar in acidic soil.

    Science.gov (United States)

    Sheng, Yaqi; Zhan, Yu; Zhu, Lizhong

    2016-12-01

    Biochar application in soil has been proposed as a promising method for carbon sequestration. While factors affecting its carbon sequestration potential have been widely investigated, the number of studies on the effect of soil pH is limited. To investigate the carbon sequestration potential of biochar across a series of soil pH levels, the total carbon emission, CO 2 release from inorganic carbon, and phospholipid fatty acids (PLFAs) of six soils with various pH levels were compared after the addition of straw biochar produced at different pyrolysis temperatures. The results show that the acidic soils released more CO 2 (1.5-3.5 times higher than the control) after the application of biochar compared with neutral and alkaline soils. The degradation of both native soil organic carbon (SOC) and biochar were accelerated. More inorganic CO 2 release in acidic soil contributed to the increased degradation of biochar. Higher proportion of gram-positive bacteria in acidic soil (25%-36%) was responsible for the enhanced biochar degradation and simultaneously co-metabolism of SOC. In addition, lower substrate limitation for bacteria, indicated by higher C-O stretching after the biochar application in the acidic soil, also caused more CO 2 release. In addition to the soil pH, other factors such as clay contents and experimental duration also affected the phsico-chemical and biotic processes of SOC dynamics. Gram-negative/gram-positive bacteria ratio was found to be negatively related to priming effects, and suggested to serve as an indicator for priming effect. In general, the carbon sequestration potential of rice-straw biochar in soil reduced along with the decrease of soil pH especially in a short-term. Given wide spread of acidic soils in China, carbon sequestration potential of biochar may be overestimated without taking into account the impact of soil pH. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

    Science.gov (United States)

    Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

    2015-01-01

    The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

  6. Response comment: Carbon sequestration on Mars

    Science.gov (United States)

    Edwards, Christopher; Ehlmann, Bethany L.

    2016-01-01

    Martian atmospheric pressure has important implications for the past and present habitability of the planet, including the timing and causes of environmental change. The ancient Martian surface is strewn with evidence for early water bound in minerals (e.g., Ehlmann and Edwards, 2014) and recorded in surface features such as large catastrophically created outflow channels (e.g., Carr, 1979), valley networks (Hynek et al., 2010; Irwin et al., 2005), and crater lakes (e.g., Fassett and Head, 2008). Using orbital spectral data sets coupled with geologic maps and a set of numerical spectral analysis models, Edwards and Ehlmann (2015) constrained the amount of atmospheric sequestration in early Martian rocks and found that the majority of this sequestration occurred prior to the formation of the early Hesperian/late Noachian valley networks (Fassett and Head, 2011; Hynek et al., 2010), thus implying the atmosphere was already thin by the time these surface-water-related features were formed.

  7. Payments for carbon sequestration to alleviate development pressure in a rapidly urbanizing region

    Science.gov (United States)

    Smith, Jordan W.; Dorning, Monica; Shoemaker, Douglas A.; Méley, Andréanne; Dupey, Lauren; Meentemeyer, Ross K.

    2017-01-01

    The purpose of this study was to determine individuals' willingness to enroll in voluntary payments for carbon sequestration programs through the use of a discrete choice experiment delivered to forest owners living in the rapidly urbanizing region surrounding Charlotte, North Carolina. We examined forest owners' willingness to enroll in payments for carbon sequestration policies under different levels of financial incentives (annual revenue), different contract lengths, and different program administrators (e.g., private companies versus a state or federal agency). We also examined the influence forest owners' sense of place had on their willingness to enroll in hypothetical programs. Our results showed a high level of ambivalence toward participating in payments for carbon sequestration programs. However, both financial incentives and contract lengths significantly influenced forest owners' intent to enroll. Neither program administration nor forest owners' sense of place influenced intent to enroll. Although our analyses indicated that payments from carbon sequestration programs are not currently competitive with the monetary returns expected from timber harvest or property sales, certain forest owners might see payments for carbon sequestration programs as a viable option for offsetting increasing tax costs as development encroaches and property values rise.

  8. Chronic idiopathic thrombocytopenic purpura (ITP): site of platelet sequestration and results of splenectomy

    International Nuclear Information System (INIS)

    Gugliotta, L.; Guarini, A.; Motta, M.R.; Bachetti, G.; Tura, S.; Isacchi, G.; Ciccone, F.; Lattarini, C.; Mazzucconi, M.G.; Mandelli, F.; Baccarani, M.

    1981-01-01

    51 Cr-platelet kinetics study was performed in 197 patients with chronic ITP after corticosteroid therapy had failed to induce a long lasting remission. The incidence of splenic, spleno-hepatic, hepatic and diffuse platelet sequestration site was 58%, 17%, 6% and 19%, respectively. Splenic and spleno-hepatic sequestration sites were more frequent in patients less than 30 years old and in patients with a platelet count lower than 50 x 10 9 /l. 111 patients were splenectomized shortly after the study. Normalization of the platelet count was obtained more frequently in patients with splenic and spleno-hepatic sequestration than in the others. Labelled platelet sequestration site was the best predictor of the outcome of splenectomy. Platelet kinetics is a non-invasive investigation that should be performed early after the diagnosis of chronic ITP in all patients eligible for splenectomy. (author)

  9. Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

    Science.gov (United States)

    Navez, Julie; Hubert, Catherine; Gigot, Jean-François; Navez, Benoit; Lambert, Catherine; Jamar, François; Danse, Etienne; Lannoy, Valérie; Jabbour, Nicolas

    2015-01-01

    Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by (111)Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100 × 10(9)/L, response (R) for PC≥30 × 10(9)/L and splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1-235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR = 1.025 by one-year increase, 95% CI [1.004-1.047], p = 0.020) and pre-operative PC (HR = 0.112 for > 100 versus splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.

  10. Land-use change and carbon sinks: Econometric estimation of the carbon sequestration supply function; FINAL

    International Nuclear Information System (INIS)

    Lubowski, Ruben N.; Plantinga, Andrew J.; Stavins, Robert N.

    2001-01-01

    Increased attention by policy makers to the threat of global climate change has brought with it considerable interest in the possibility of encouraging the expansion of forest area as a means of sequestering carbon dioxide. The marginal costs of carbon sequestration or, equivalently, the carbon sequestration supply function will determine the ultimate effects and desirability of policies aimed at enhancing carbon uptake. In particular, marginal sequestration conts are the critical statistic for identifying a cost-effective policy mix to mitigate net carbon dioxide emissions. We develop a framework for conducting an econometric analysis of land use for the forty-eight contiguous United States and employing it to estimate the carbon sequestration supply function. By estimating the opportunity costs of land on the basis of econometric evidence of landowners' actual behavior, we aim to circumvent many of the shortcomings of previous sequestration cost assessments. By conducting the first nationwide econometric estimation of sequestration costs, endogenizing prices for land-based commodities, and estimating land-use transition probabilities in a framework that explicitly considers the range of land-use alternatives, we hope to provide better estimates eventually of the true costs of large-scale carbon sequestration efforts. In this way, we seek to add to understanding of the costs and potential of this strategy for addressing the threat of global climate change

  11. GLI1, a master regulator of the hallmark of pancreatic cancer.

    Science.gov (United States)

    Kasai, Kenji

    2016-12-01

    Hedgehog signaling is highly conserved across species and governs proper embryonic development. Germline gene mutations that reduce this signaling activity cause a variety of developmental abnormalities such as holoprosencephaly, while those that enhance Hedgehog signaling activity induce a tumor-predisposition condition Nevoid basal cell carcinoma syndrome. Furthermore, dysregulated activation of Hedgehog signaling has been recognized in various sporadic malignancies, including pancreatic adenocarcinoma. Pancreatic adenocarcinoma develops through a multistep carcinogenesis starting with oncogenic mutation of the KRAS gene. During this process, precancerous or cancer cells secrete Hedgehog ligand proteins to promote characteristic desmoplastic stroma around the cells, which in turn activates the expression of the downstream transcription factor GLI1 inside the cells. The quantitative and spatiotemporal dysregulation of GLI1 subsequently leads to the expression of transcriptional target genes of GLI1 that govern the hallmark of malignant properties. Here, after a brief introductory outline, a perspective is offered of Hedgehog signaling with a special focus on the role of GLI1 in pancreatic carcinogenesis. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  12. CT imaging of splenic sequestration in sickle cell disease

    International Nuclear Information System (INIS)

    Sheth, S.; Piomelli, S.; Ruzal-Shapiro, C.; Berdon, W.E.

    2000-01-01

    Pooling of blood in the spleen is a frequent occurrence in children with sickle cell diseases, particularly in the first few years of life, resulting in what is termed ''splenic sequestration crisis.'' The spectrum of severity in this syndrome is wide, ranging from mild splenomegaly to massive enlargement, circulatory collapse, and even death. The diagnosis is usually clinical, based on the enlargement of the spleen with a drop in hemoglobin level by >2 g/dl, and it is rare that imaging studies are ordered. However, in the patient who presents to the emergency department with non-specific findings of an acute abdomen, it is important to recognize the appearance of sequestration on imaging studies. We studied seven patients utilizing contrast-enhanced CT scans and found two distinct patterns - multiple, peripheral, non-enhancing low-density areas or large, diffuse areas of low density in the majority of the splenic tissue. Although radiological imaging is not always necessary to diagnose splenic sequestration, in those situations where this diagnosis is not immediately obvious, it makes an important clarifying contribution. (orig.)

  13. Potential Hydrogeomechanical Impacts of Geological CO2 Sequestration

    Science.gov (United States)

    McPherson, B. J.; Haerer, D.; Han, W.; Heath, J.; Morse, J.

    2006-12-01

    Long-term sequestration of anthropogenic "greenhouse gases" such as CO2 is a proposed approach to managing climate change. Deep brine reservoirs in sedimentary basins are possible sites for sequestration, given their ubiquitous nature. We used a mathematical sedimentary basin model, including coupling of multiphase CO2-groundwater flow and rock deformation, to evaluate residence times in possible brine reservoir storage sites, migration patterns and rates away from such sites, and effects of CO2 injection on fluid pressures and rock strain. Study areas include the Uinta and Paradox basins of Utah, the San Juan basin of New Mexico, and the Permian basin of west Texas. Regional-scale hydrologic and mechanical properties, including the presence of fracture zones, were calibrated using laboratory and field data. Our initial results suggest that, in general, long-term (~100 years or more) sequestration in deep brine reservoirs is possible, if guided by robust structural and hydrologic data. However, specific processes must be addressed to characterize and minimize risks. In addition to CO2 migration from target sequestration reservoirs into other reservoirs or to the land surface, another environmental issue is displacement of brines into freshwater aquifers. We evaluated the potential for such unintended aquifer contamination by displacement of brines out of adjacent sealing layers such as marine shales. Results suggest that sustained injection of CO2 may incur significant brine displacement out of adjacent sealing layers, depending on the injection history, initial brine composition, and hydrologic properties of both reservoirs and seals. Model simulations also suggest that as injection-induced overpressures migrate, effective stresses may follow this migration under some conditions, as will associated rock strain. Such "strain migration" may lead to induced or reactivated fractures or faults, but can be controlled through reservoir engineering.

  14. HedgeHOGS: A Rapid Nuclear Hedge Sizing and Analysis Tool

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, Adam F. [United States Military Academy, West Point, NY (United States); Steinfeldt, Bradley Alexander [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Lafleur, Jarret Marshall [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Hawley, Marilyn F. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Shannon, Lisa M. [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2017-07-01

    The U.S. nuclear stockpile hedge is an inventory of non-deployed nuclear warheads and a force structure capable of deploying those warheads. Current guidance is to retain this hedge to mitigate the risk associated with the technical failure of any single warhead type or adverse geopolitical developments that could require augmentation of the force. The necessary size of the hedge depends on the composition of the nuclear stockpile and assumed constraints. Knowing the theoretical minimum hedge given certain constraints is useful when considering future weapons policy. HedgeHOGS, an Excel-based tool, was developed to enable rapid calculation of the minimum hedge size associated with varying active stockpile composition and hedging strategies.

  15. Two novel mixed-ligand complexes containing organosulfonate ligands.

    Science.gov (United States)

    Li, Mingtian; Huang, Jun; Zhou, Xuan; Fang, Hua; Ding, Liyun

    2008-07-01

    The structures reported herein, viz. bis(4-aminonaphthalene-1-sulfonato-kappaO)bis(4,5-diazafluoren-9-one-kappa(2)N,N')copper(II), [Cu(C(10)H(8)NO(3)S)(2)(C(11)H(6)N(2)O)(2)], (I), and poly[[[diaquacadmium(II)]-bis(mu-4-aminonaphthalene-1-sulfonato)-kappa(2)O:N;kappa(2)N:O] dihydrate], {[Cd(C(10)H(8)NO(3)S)(2)(H(2)O)(2)].2H(2)O}(n), (II), are rare examples of sulfonate-containing complexes where the anion does not fulfill a passive charge-balancing role, but takes an active part in coordination as a monodentate and/or bridging ligand. Monomeric complex (I) possesses a crystallographic inversion center at the Cu(II) atom, and the asymmetric unit contains one-half of a Cu atom, one complete 4-aminonaphthalene-1-sulfonate (ans) ligand and one 4,5-diazafluoren-9-one (DAFO) ligand. The Cu(II) atom has an elongated distorted octahedral coordination geometry formed by two O atoms from two monodentate ans ligands and by four N atoms from two DAFO molecules. Complex (II) is polymeric and its crystal structure is built up by one-dimensional chains and solvent water molecules. Here also the cation (a Cd(II) atom) lies on a crystallographic inversion center and adopts a slightly distorted octahedral geometry. Each ans anion serves as a bridging ligand linking two Cd(II) atoms into one-dimensional infinite chains along the [010] direction, with each Cd(II) center coordinated by four ans ligands via O and N atoms and by two aqua ligands. In both structures, there are significant pi-pi stacking interactions between adjacent ligands and hydrogen bonds contribute to the formation of two- and three-dimensional networks.

  16. Cooperation of Indian Hedgehog and Vascular Endothelial Growth Factor in Tumor Angiogenesis and Growth in Human Hepatocellular Carcinomas, an Immunohistochemical Study.

    Science.gov (United States)

    Li, Yang; Liu, Yang; Wang, Guangxi; Wang, Yuxiang; Guo, Limei

    2018-04-07

    The Hedgehog pathway was recently shown to be involved in vascular development and neovascularization in human embryogenesis and disease. However, the role of Hedgehog pathway in modulating tumor angiogenesis is still unexplored. In the current study, we investigated the expression of Indian Hedgehog (Ihh) and vascular endothelial cell growth factor (VEGF) in human hepatocellular carcinomas (HCCs) with immunohistochemical staining and compared the immunoreaction data with various clinicopathologic characteristics. Immunoreactivity of Ihh and VEGF proteins was observed in 61.5% (56/91) and 64.5% (59/91) cases of HCC tumor tissues, respectively, which was considerably higher than the adjacent nonmalignant tissues. Ihh protein was observed predominantly in the cytoplasm of the tumor cells with a staining pattern of which was sparse and dot-like, or circular around the cell membrane. VEGF protein was expressed heterogenously in the cytoplasm in tumor cells and was negative in peritumoral areas in all cases. CD34 showed diffuse staining in the tumor parenchyma in most HCC specimens. The association of expression of Ihh and VEGF with tumor size was statistically significant (PIhh and VEGF proteins in HCC (r=0.6, PIhh and CD34 staining (r=0.261, P=0.012). Our findings suggest that Ihh is involved in the development of HCC. These findings are also consistent with the concept that cooperation of Ihh and VEGF modulate HCC tumor angiogenesis and growth.

  17. Multi-slice spiral CT diagnosis of arterial sequestration

    International Nuclear Information System (INIS)

    Yu Hong; Li Huimin; Liu Shiyuan; Xiao Xiangsheng

    2010-01-01

    Objective: The purpose of this study was to present the characteristic features on MSCT angiography of arterial sequestration. Methods: The MSCT images of 5 patients with arterial sequestration were retrospectively reviewed. All patients underwent MSCT contrast-enhanced angiography. 3D rendering was made to evaluate the lung parenchyma, bronchial system, and vascular anatomy. Results: All 5 cases demonstrated the anomalous systemic artery (ASA) as an isolated and tortuous artery arising from the descending thoracic aorta, taking a sigmoid course and running along with airway, entering the basal segments of the left lowed lobe. The inferior pulmonary vein (IPV) was significantly engorged. The typical AS was diagnosed in 4 patients. Its ASA intercrossed with the IPV and two branches entering segments 7 and 8 over the IPV, and two branches entering segments 9 and 10 under the IPV. The volume of involved lung shrunk with the artery markedly engorged. A characteristic avascular section was found between the pulmonary artery supplying area and the ASA supplying area, and the bronchi did not accompany the arteries. One was diagnosed atypical AS because of coexistence with bronchial atresia. Conclusion: The arterial sequestration had characteristic MSCT findings. The typical type can be definitely diagnosed, but the atypical type needs further three-dimensional analysis. (authors)

  18. Long-term nitrogen regulation of forest carbon sequestration

    Science.gov (United States)

    Yang, Y.; Luo, Y.

    2009-12-01

    It is well established that nitrogen (N) limits plant production but unclear how N regulates long-term terrestrial carbon (C) sequestration in response to rising atmospheric C dioxide (CO2)(Luo et al., 2004). Most experimental evidence on C-N interactions is primarily derived from short-term CO2 manipulative studies (e.g. Oren et al., 2001; Reich et al., 2006a), which abruptly increase C inputs into ecosystems and N demand from soil while atmospheric CO2 concentration in the real world is gradually increasing over time (Luo & Reynolds, 1999). It is essential to examine long-term N regulations of C sequestration in natural ecosystems. Here we present results of a synthesis of more than 100 studies on long-term C-N interactions during secondary succession. C significantly accumulates in plant, litter and forest floor in most studies, and in mineral soil in one-third studies during stand development. Substantial increases in C stock are tightly coupled with N accretion. The C: N ratio in plant increases with stand age in most cases, but remains relatively constant in litter, forest floor and mineral soil. Our results suggest that natural ecosystems could have the intrinsic capacity to maintain long-term C sequestration through external N accrual, high N use efficiency, and efficient internal N cycling.

  19. SOUTHEAST REGIONAL CARBON SEQUESTRATION PARTNERSHIP (SECARB)

    Energy Technology Data Exchange (ETDEWEB)

    Kenneth J. Nemeth

    2004-09-01

    The Southeast Regional Carbon Sequestration Partnership (SECARB) is on schedule and within budget projections for the work completed during the first year of its two year program. Work during the semiannual period (third and fourth quarter) of the project (April 1--September 30, 2004) was conducted within a ''Task Responsibility Matrix.'' Under Task 1.0 Define Geographic Boundaries of the Region, Texas and Virginia were added during the second quarter of the project and no geographical changes occurred during the third or fourth quarter of the project. Under Task 2.0 Characterize the Region, general mapping and screening of sources and sinks has been completed, with integration and Geographical Information System (GIS) mapping ongoing. The first step focused on the macro level characterization of the region. Subsequent characterization will focus on smaller areas having high sequestration potential. Under Task 3.0 Identify and Address Issues for Technology Deployment, SECARB has completed a preliminary assessment of safety, regulatory, permitting, and accounting frameworks within the region to allow for wide-scale deployment of promising terrestrial and geologic sequestration approaches. Under Task 4.0 Develop Public Involvement and Education Mechanisms, SECARB has conducted a survey and focus group meeting to gain insight into approaches that will be taken to educate and involve the public. Task 5.0 and 6.0 will be implemented beginning October 1, 2004. Under Task 5.0 Identify the Most Promising Capture, Sequestration, and Transport Options, SECARB will evaluate findings from work performed during the first year and shift the focus of the project team from region-wide mapping and characterization to a more detailed screening approach designed to identify the most promising opportunities. Under Task 6.0 Prepare Action Plans for Implementation and Technology Validation Activity, the SECARB team will develop an integrated approach to implementing

  20. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2017-06-15

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

  1. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

    International Nuclear Information System (INIS)

    Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

    2017-01-01

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

  2. Linking salinity stress tolerance with tissue-specific Na+ sequestration in wheat roots

    Directory of Open Access Journals (Sweden)

    Honghong eWu

    2015-02-01

    Full Text Available Salinity stress tolerance is a physiologically complex trait that is conferred by the large array of interacting mechanisms. Among these, vacuolar Na+ sequestration has always been considered as one of the key components differentiating between sensitive and tolerant species and genotypes. However, vacuolar Na+ sequestration has been rarely considered in the context of the tissue-specific expression and regulation of appropriate transporters contributing to Na+ removal from the cytosol. In this work, six bread wheat varieties contrasting in their salinity tolerance (three tolerant and three sensitive were used to understand the essentiality of vacuolar Na+ sequestration between functionally different root tissues, and link it with the overall salinity stress tolerance in this species. Roots of 4-d old wheat seedlings were treated with 100 mM NaCl for 3 days, and then Na+ distribution between cytosol and vacuole was quantified by CoroNa Green fluorescent dye imaging. Our major observations were as follows: 1 salinity stress tolerance correlated positively with vacuolar Na+ sequestration ability in the mature root zone but not in the root apex; 2 Contrary to expectations, cytosolic Na+ levels in root meristem were significantly higher in salt tolerant than sensitive group, while vacuolar Na+ levels showed an opposite trend. These results are interpreted as meristem cells playing a role of the salt sensor; 3 No significant difference in the vacuolar Na+ sequestration ability was found between sensitive and tolerant group in either transition or elongation zones; 4 The overall Na+ accumulation was highest in the elongation zone, suggesting its role in osmotic adjustment and turgor maintenance required to drive root expansion growth. Overall, the reported results suggest high tissue-specificity of Na+ uptake, signalling, and sequestration in wheat root. The implications of these findings for plant breeding for salinity stress tolerance are discussed.

  3. Using silviculture to influence carbon sequestration in southern Appalachian spruce-fir forests

    Science.gov (United States)

    Patrick T. Moore; R. Justin DeRose; James N. Long; Helga. van Miegroet

    2012-01-01

    Enhancement of forest growth through silvicultural modification of stand density is one strategy for increasing carbon (C) sequestration. Using the Fire and Fuels Extension of the Forest Vegetation Simulator, the effects of even-aged, uneven-aged and no-action management scenarios on C sequestration in a southern Appalachian red spruce-Fraser fir forest were modeled....

  4. An Integrated Approach Identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated Genes in Developing Cerebellum and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2008-01-01

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.

  5. Development and validation of a testing protocol for carbon sequestration using a controlled environment.

    Science.gov (United States)

    2012-05-01

    Carbon footprints, carbon credits and associated carbon sequestration techniques are rapidly becoming part : of how environmental mitigation business is conducted, not only in Texas but globally. Terrestrial carbon : sequestration is the general term...

  6. Carbon sequestration via wood burial

    Directory of Open Access Journals (Sweden)

    Zeng Ning

    2008-01-01

    Full Text Available Abstract To mitigate global climate change, a portfolio of strategies will be needed to keep the atmospheric CO2 concentration below a dangerous level. Here a carbon sequestration strategy is proposed in which certain dead or live trees are harvested via collection or selective cutting, then buried in trenches or stowed away in above-ground shelters. The largely anaerobic condition under a sufficiently thick layer of soil will prevent the decomposition of the buried wood. Because a large flux of CO2 is constantly being assimilated into the world's forests via photosynthesis, cutting off its return pathway to the atmosphere forms an effective carbon sink. It is estimated that a sustainable long-term carbon sequestration potential for wood burial is 10 ± 5 GtC y-1, and currently about 65 GtC is on the world's forest floors in the form of coarse woody debris suitable for burial. The potential is largest in tropical forests (4.2 GtC y-1, followed by temperate (3.7 GtC y-1 and boreal forests (2.1 GtC y-1. Burying wood has other benefits including minimizing CO2 source from deforestation, extending the lifetime of reforestation carbon sink, and reducing fire danger. There are possible environmental impacts such as nutrient lock-up which nevertheless appears manageable, but other concerns and factors will likely set a limit so that only part of the full potential can be realized. Based on data from North American logging industry, the cost for wood burial is estimated to be $14/tCO2($50/tC, lower than the typical cost for power plant CO2 capture with geological storage. The cost for carbon sequestration with wood burial is low because CO2 is removed from the atmosphere by the natural process of photosynthesis at little cost. The technique is low tech, distributed, easy to monitor, safe, and reversible, thus an attractive option for large-scale implementation in a world-wide carbon market.

  7. Decarbonization and sequestration for mitigating global warming

    International Nuclear Information System (INIS)

    Steinberg, M.

    2000-01-01

    Mitigating the global warming greenhouse effect while maintaining a fossil fuel economy, requires improving efficiency of utilization of fossil fuels, use of high hydrogen content fossil fuels, decarbonization of fossil fuels, and sequestering of carbon and CO 2 applied to all the sectors of the economy, electric power generation, transportation, and industrial, and domestic power and heat generation. Decarbonization means removal of carbon as C or CO 2 either before or after fossil fuel combustion and sequestration means disposal of the recovered C or CO 2 including its utilization. Removal and recovery of CO 2 from power generation plants and sequestration in the ocean represents one possibility of making a major impact on reducing CO 2 emissions to the atmosphere. This paper will briefly review the progress made in ocean disposal and present some alternative schemes. (author)

  8. AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

    Science.gov (United States)

    Ravindranath, Pradeep Anand; Sanner, Michel F.

    2016-01-01

    Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

  9. Considerations in forecasting the demand for carbon sequestration and biotic storage technologies

    Energy Technology Data Exchange (ETDEWEB)

    Trexler, M.C. [Trexler and Associates, Inc., Portland, OR (United States)

    1997-12-31

    The Intergovernmental Panel on Climate Change (IPCC) has identified forestry and other land-use based mitigation measures as possible sources and sinks of greenhouse gases. An overview of sequestration and biotic storage is presented, and the potential impacts of the use of carbon sequestration as a mitigation technology are briefly noted. Carbon sequestration is also compare to other mitigation technologies. Biotic mitigation technologies are concluded to be a legitimate and potentially important part of greenhouse gas mitigation due to their relatively low costs, ancillary benefits, and climate impact. However, not all biotic mitigation techniques perfectly match the idealized definition of a mitigation measure, and policies are becoming increasingly biased against biotic technologies.

  10. Hydrothermal carbonization of glucose in saline solution: sequestration of nutrients on carbonaceous materials

    Directory of Open Access Journals (Sweden)

    Jessica Nover

    2016-02-01

    Full Text Available In this study, feasibility of selected nutrient sequestration during hydrothermal carbonization (HTC was tested for three different HTC temperatures (180, 230, and 300 °C. To study the nutrient sequestration in solid from liquid solution, sugar and salt solutions were chosen as HTC feedstock. Glucose was used as carbohydrate source and various salts e.g., ammonium hydrophosphate, potassium chloride, potassium sulfate, and anhydrous ferric chloride were used as source of nitrogen and phosphorus, potassium, and iron, respectively. Solid hydrochar was extensively characterized by means of elemental, ICP-OES, SEM-EDX, surface area, pore volume and size, and ATR-FTIR to determine nutrients’ sequestration as well as hydrochar quality variation with HTC temperatures. The spherical mesoporous hydrochars produced during HTC have low surface area in the range of 1.0–3.5 m2 g−1. Hydrochar yield was increased about 10% with the increase of temperature from 180 °C to 300 °C. Nutrient sequestration was also increased with HTC temperature. In fact, around 71, 31, and 23 wt% nitrogen, iron, and phosphorus were sequestered at 300 °C, respectively. Potassium sequestration was very low throughout the HTC and maximum 5.2% was observed in solid during HTC.

  11. Carbon sequestration in the U.S. forest sector from 1990 to 2010

    Science.gov (United States)

    Peter B. Woodbury; James E. Smith; Linda S. Heath

    2007-01-01

    Forest inventory data supplemented with data from intensive research sites and models were used to estimate carbon stocks and sequestration rates in U.S. forests, including effects of land use change. Data on the production of wood products and emission from decomposition were used to estimate carbon stocks and sequestration rates in wood products and landfills. From...

  12. Leukotriene synthesis is required for hedgehog-dependent neurite projection in neuralized embryoid bodies but not for motor neuron differentiation

    NARCIS (Netherlands)

    Bijlsma, Maarten F.; Peppelenbosch, Maikel P.; Spek, C. Arnold; Roelink, Henk

    The hedgehog (Hh) pathway is required for many developmental processes,. as well as for adult homeostasis. Although all known effects of Hh signaling affecting patterning and differentiation are mediated by members of the Gli family of zinc ringer transcription factors, we demonstrate that the

  13. Hedgehog signal activation coordinates proliferation and differentiation of fetal liver progenitor cells

    International Nuclear Information System (INIS)

    Hirose, Yoshikazu; Itoh, Tohru; Miyajima, Atsushi

    2009-01-01

    Hedgehog (Hh) signaling plays crucial roles in development and homeostasis of various organs. In the adult liver, it regulates proliferation and/or viability of several types of cells, particularly under injured conditions, and is also implicated in stem/progenitor cell maintenance. However, the role of this signaling pathway during the normal developmental process of the liver remains elusive. Although Sonic hedgehog (Shh) is expressed in the ventral foregut endoderm from which the liver derives, the expression disappears at the onset of the liver bud formation, and its possible recurrence at the later stages has not been investigated. Here we analyzed the activation and functional relevance of Hh signaling during the mouse fetal liver development. At E11.5, Shh and an activation marker gene for Hh signaling, Gli1, were expressed in Dlk + hepatoblasts, the fetal liver progenitor cells, and the expression was rapidly decreased thereafter as the development proceeded. In the culture of Dlk + hepatoblasts isolated from the E11.5 liver, activation of Hh signaling stimulated their proliferation and this effect was cancelled by a chemical Hh signaling inhibitor, cyclopamine. In contrast, hepatocyte differentiation of Dlk + hepatoblasts in vitro as manifested by the marker gene expression and acquisition of ammonia clearance activity was significantly inhibited by forced activation of Hh signaling. Taken together, these results demonstrate the temporally restricted manner of Hh signal activation and its role in promoting the hepatoblast proliferation, and further suggest that the pathway needs to be shut off for the subsequent hepatic differentiation of hepatoblasts to proceed normally.

  14. Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy

    DEFF Research Database (Denmark)

    Kristensen, Lone Krøldrup; Kjaergaard, S; Kirchhoff, Marianne

    2012-01-01

    with muscular hypertrophy and mildly retarded psychomotor development. Array-CGH identified a small duplication of 7q36.3 including the Sonic Hedgehog (SHH) gene in both the aborted foetus and the live born male sib. Neither of the parents carried the 7q36.3 duplication. The consequences of overexpression...

  15. CO2 geological sequestration: state of art in Italy and abroad

    International Nuclear Information System (INIS)

    Quattrocchi, Fedora; Bencini, Roberto

    2005-01-01

    This paper proposes a wide scenario on the state of art in Italy and abroad of industrial CO 2 geological sequestration, with particular attention to Weyburn Project. Geochemical monitoring techniques are described, mentioning also geophysical monitoring techniques for CO 2 injected into the soil. Critical choices and objections in Italy to a complete use of clean fossil fuels, hydrogen carrier, clean coal technologies: all of these approaches require geological sequestration of CO 2 [it

  16. Carbon sequestration, optimum forest rotation and their environmental impact

    International Nuclear Information System (INIS)

    Kula, Erhun; Gunalay, Yavuz

    2012-01-01

    Due to their large biomass forests assume an important role in the global carbon cycle by moderating the greenhouse effect of atmospheric pollution. The Kyoto Protocol recognises this contribution by allocating carbon credits to countries which are able to create new forest areas. Sequestrated carbon provides an environmental benefit thus must be taken into account in cost–benefit analysis of afforestation projects. Furthermore, like timber output carbon credits are now tradable assets in the carbon exchange. By using British data, this paper looks at the issue of identifying optimum felling age by considering carbon sequestration benefits simultaneously with timber yields. The results of this analysis show that the inclusion of carbon benefits prolongs the optimum cutting age by requiring trees to stand longer in order to soak up more CO 2 . Consequently this finding must be considered in any carbon accounting calculations. - Highlights: ► Carbon sequestration in forestry is an environmental benefit. ► It moderates the problem of global warming. ► It prolongs the gestation period in harvesting. ► This paper uses British data in less favoured districts for growing Sitka spruce species.

  17. Carbon sequestration, optimum forest rotation and their environmental impact

    Energy Technology Data Exchange (ETDEWEB)

    Kula, Erhun, E-mail: erhun.kula@bahcesehir.edu.tr [Department of Economics, Bahcesehir University, Besiktas, Istanbul (Turkey); Gunalay, Yavuz, E-mail: yavuz.gunalay@bahcesehir.edu.tr [Department of Business Studies, Bahcesehir University, Besiktas, Istanbul (Turkey)

    2012-11-15

    Due to their large biomass forests assume an important role in the global carbon cycle by moderating the greenhouse effect of atmospheric pollution. The Kyoto Protocol recognises this contribution by allocating carbon credits to countries which are able to create new forest areas. Sequestrated carbon provides an environmental benefit thus must be taken into account in cost-benefit analysis of afforestation projects. Furthermore, like timber output carbon credits are now tradable assets in the carbon exchange. By using British data, this paper looks at the issue of identifying optimum felling age by considering carbon sequestration benefits simultaneously with timber yields. The results of this analysis show that the inclusion of carbon benefits prolongs the optimum cutting age by requiring trees to stand longer in order to soak up more CO{sub 2}. Consequently this finding must be considered in any carbon accounting calculations. - Highlights: Black-Right-Pointing-Pointer Carbon sequestration in forestry is an environmental benefit. Black-Right-Pointing-Pointer It moderates the problem of global warming. Black-Right-Pointing-Pointer It prolongs the gestation period in harvesting. Black-Right-Pointing-Pointer This paper uses British data in less favoured districts for growing Sitka spruce species.

  18. CXCL14 is a candidate biomarker for Hedgehog signalling in idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Jia, Guiquan; Chandriani, Sanjay; Abbas, Alexander R; DePianto, Daryle J; N'Diaye, Elsa N; Yaylaoglu, Murat B; Moore, Heather M; Peng, Ivan; DeVoss, Jason; Collard, Harold R; Wolters, Paul J; Egen, Jackson G; Arron, Joseph R

    2017-09-01

    Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity. We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor. Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was CXCL14 , which encodes a soluble secreted chemokine whose expression is inhibited in vitro by the addition of vismodegib. CXCL14 expression was induced by SHh overexpression in mouse lung. Circulating CXCL14 protein levels were significantly higher in plasma from IPF patients than controls. In cancer patients, circulating CXCL14 levels were significantly reduced upon vismodegib treatment. CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF. Post-results, NCT00968981. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. CARBON SEQUESTRATION: A METHODS COMPARATIVE ANALYSIS

    International Nuclear Information System (INIS)

    Christopher J. Koroneos; Dimitrios C. Rovas

    2008-01-01

    All human activities are related with the energy consumption. Energy requirements will continue to rise, due to the modern life and the developing countries growth. Most of the energy demand emanates from fossil fuels. Fossil fuels combustion has negative environmental impacts, with the CO 2 production to be dominating. The fulfillment of the Kyoto protocol criteria requires the minimization of CO 2 emissions. Thus the management of the CO 2 emissions is an urgent matter. The use of appliances with low energy use and the adoption of an energy policy that prevents the unnecessary energy use, can play lead to the reduction of carbon emissions. A different route is the introduction of ''clean'' energy sources, such as renewable energy sources. Last but not least, the development of carbon sequestration methods can be promising technique with big future potential. The objective of this work is the analysis and comparison of different carbon sequestration and deposit methods. Ocean deposit, land ecosystems deposit, geological formations deposit and radical biological and chemical approaches will be analyzed

  20. Ligand Depot: a data warehouse for ligands bound to macromolecules.

    Science.gov (United States)

    Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

    2004-09-01

    Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

  1. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    Science.gov (United States)

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  2. Indian hedgehog contributes to human cartilage endplate degeneration.

    Science.gov (United States)

    Wang, Shaowei; Yang, Kun; Chen, Shuai; Wang, Jiying; Du, Guoqing; Fan, Shunwu; Wei, Lei

    2015-08-01

    To determine the role of Indian hedgehog (Ihh) signaling in human cartilage endplate (CEP) degeneration. CEP-degenerated tissues from patients with Modic I or II changes (n = 9 and 45, respectively) and normal tissues from vertebral burst fracture patients (n = 17) were collected. Specimens were either cut into slices for organ culture ex vivo or digested to isolate chondrocytes for cell culture in vitro. Ihh expression and the effect of Ihh on cartilage degeneration were determined by investigating degeneration markers in this study. Ihh expression and cartilage degeneration markers significantly increased in the Modic I and II groups. The expression of cartilage degeneration markers was positively correlated with degeneration severity. Gain-of-function for Ihh promoted expression of cartilage degeneration markers in vitro, while loss-of-function for Ihh inhibited their expression both in vitro and ex vivo. These findings demonstrated that Ihh promotes CEP degeneration. Blocking Ihh pathway has potential clinical usage for attenuating CEP degeneration.

  3. Sonic Hedgehog Signaling Drives Mitochondrial Fragmentation by Suppressing Mitofusins in Cerebellar Granule Neuron Precursors and Medulloblastoma.

    Science.gov (United States)

    Malhotra, Anshu; Dey, Abhinav; Prasad, Niyathi; Kenney, Anna Marie

    2016-01-01

    Sonic hedgehog (Shh) signaling is closely coupled with bioenergetics of medulloblastoma, the most common malignant pediatric brain tumor. Shh-associated medulloblastoma arises from cerebellar granule neuron precursors (CGNP), a neural progenitor whose developmental expansion requires signaling by Shh, a ligand secreted by the neighboring Purkinje neurons. Previous observations show that Shh signaling inhibits fatty acid oxidation although driving increased fatty acid synthesis. Proliferating CGNPs and mouse Shh medulloblastomas feature high levels of glycolytic enzymes in vivo and in vitro. Because both of these metabolic processes are closely linked to mitochondrial bioenergetics, the role of Shh signaling in mitochondrial biogenesis was investigated. This report uncovers a surprising decrease in mitochondrial membrane potential (MMP) and overall ATP production in CGNPs exposed to Shh, consistent with increased glycolysis resulting in high intracellular acidity, leading to mitochondrial fragmentation. Ultrastructural examination of mitochondria revealed a spherical shape in Shh-treated cells, in contrast to the elongated appearance in vehicle-treated postmitotic cells. Expression of mitofusin 1 and 2 was reduced in these cells, although their ectopic expression restored the MMP to the nonproliferating state and the morphology to a fused, interconnected state. Mouse Shh medulloblastoma cells featured drastically impaired mitochondrial morphology, restoration of which by ectopic mitofusin expression was also associated with a decrease in the expression of Cyclin D2 protein, a marker for proliferation. This report exposes a novel role for Shh in regulating mitochondrial dynamics and rescue of the metabolic profile of tumor cells to that of nontransformed, nonproliferating cells and represents a potential avenue for development of medulloblastoma therapeutics. ©2015 American Association for Cancer Research.

  4. Bile acid sequestrants : more than simple resins

    NARCIS (Netherlands)

    Out, Carolien; Groen, Albert K.; Brufau, Gemma

    Purpose of review Bile acid sequestrants (BAS) have been used for more than 50 years in the treatment of hypercholesterolemia. The last decade, bile acids are emerging as integrated regulators of metabolism via induction of various signal transduction pathways. Consequently, BAS treatment may exert

  5. Analysis of ex situ processes of CO2 sequestration. Final report

    International Nuclear Information System (INIS)

    Touze, S.; Bourgeois, F.; Baranger, P.; Durst, P.

    2004-01-01

    The aim of this study is to bring quantitative elements to evaluate the validation of the CO 2 mineral sequestration to limit the greenhouse effect gases. This analysis aims to calculate the CO 2 accounting of the system (internal energy production balance the energy expend) sequestrated CO 2 and produced CO 2 . The first part detailed the possible experimental solutions. Then two carbonation processes, direct and indirect, have been chosen of the analysis. (A.L.B.)

  6. How sequestration cuts affect primary care physicians and graduate medical education.

    Science.gov (United States)

    Chauhan, Bindiya; Coffin, Janis

    2013-01-01

    On April 1, 2013, sequestration cuts went into effect impacting Medicare physician payments, graduate medical education, and many other healthcare agencies. The cuts range from 2% to 5%, affecting various departments and organizations. There is already a shortage of primary care physicians in general, not including rural or underserved areas, with limited grants for advanced training. The sequestration cuts negatively impact the future of many primary care physicians and hinder the care many Americans will receive over time.

  7. Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells.

    Science.gov (United States)

    Liu, Yanjun; DU, Fangfang; Zhao, Qiannan; Jin, Jian; Ma, Xin; Li, Huazhong

    2015-06-01

    Colon cancer has a high incidence in individuals >60-years-old. The commonly used chemotherapeutic agent, 5-fluorouracil (5-FU), has gradually lost its potency in treating colorectal cancer following the acquisition of resistance. Drug resistance is usually associated with epithelial-mesenchymal transitions (EMTs) in cancer cells. In the present study, the EMT phenotypes of two colon cancer cell lines, wild-type (HCT-8/WT) and 5-FU-resistant (HCT-8/5-FU), were characterized following the analysis of cellular migration, proliferation, morphology and molecular changes. In order to further clarify the mechanism of EMT in HCT-8/5-FU cells, the effect of EMT pathway inhibitors upon drug sensitivity was investigated. The results revealed that the Hedgehog signaling pathway inhibitor, GDC0449, reversed drug resistance. Therefore, inhibition of the Hedgehog pathway may provide a novel chemotherapeutic strategy for the treatment of patients with 5-FU-resistant colon cancer.

  8. Technological learning for carbon capture and sequestration technologies

    International Nuclear Information System (INIS)

    Riahi, Keywan; Rubin, Edward S.; Taylor, Margaret R.; Schrattenholzer, Leo; Hounshell, David

    2004-01-01

    This paper analyzes potentials of carbon capture and sequestration technologies (CCT) in a set of long-term energy-economic-environmental scenarios based on alternative assumptions for technological progress of CCT. In order to get a reasonable guide to future technological progress in managing CO 2 emissions, we review past experience in controlling sulfur dioxide (SO 2 ) emissions from power plants. By doing so, we quantify a 'learning curve' for CCT, which describes the relationship between the improvement of costs due to accumulation of experience in CCT construction. We incorporate the learning curve into the energy-modeling framework MESSAGE-MACRO and develop greenhouse gas emissions scenarios of economic, demographic, and energy demand development, where alternative policy cases lead to the stabilization of atmospheric CO 2 concentrations at 550 parts per million by volume (ppmv) by the end of the 21st century. We quantify three types of contributors to the carbon emissions mitigation: (1) demand reductions due to the increased price of energy, (2) fuel switching primarily away from coal, and (3) carbon capture and sequestration from fossil fuels. Due to the assumed technological learning, costs of the emissions reduction for CCT drop rapidly and in parallel with the massive introduction of CCT on the global scale. Compared to scenarios based on static cost assumptions for CCT, the contribution of carbon sequestration is about 50% higher in the case of learning, resulting in cumulative sequestration of CO 2 ranging from 150 to 250 billion (10 9 ) tons with carbon during the 21st century. Also, carbon values (tax) across scenarios (to meet the 550 ppmv carbon concentration constraint) are between 2% and 10% lower in the case of learning for CCT by 2100. The results illustrate that assumptions on technological change are a critical determinant of future characteristics of the energy system, indicating the importance of long-term technology policies in

  9. Soil carbon sequestration potential in semi-arid grasslands in the conservation reserve program

    Science.gov (United States)

    The Conservation Reserve Program (CRP) in the USA plays a major role in carbon (C) sequestration to help mitigate rising CO2 levels and climate change. The Southern High Plains (SHP) region contains N900.000 ha enrolled in CRP, but a regionally specific C sequestration rate has not been studied, and...

  10. Method for carbon dioxide sequestration

    Science.gov (United States)

    Wang, Yifeng; Bryan, Charles R.; Dewers, Thomas; Heath, Jason E.

    2017-12-05

    A method for geo-sequestration of a carbon dioxide includes selection of a target water-laden geological formation with low-permeability interbeds, providing an injection well into the formation and injecting supercritical carbon dioxide (SC-CO.sub.2) and water or bine into the injection well under conditions of temperature, pressure and density selected to cause the fluid to enter the formation and splinter and/or form immobilized ganglia within the formation.

  11. Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease.

    Science.gov (United States)

    Owusu-Ofori, Shirley; Remmington, Tracey

    2015-09-07

    Acute splenic sequestration crises are a complication of sickle cell disease, with high mortality rates and frequent recurrence in survivors of first attacks. Splenectomy and blood transfusion, with their consequences, are the mainstay of long-term management used in different parts of the world. This is a 2015 update of a Cochrane review first published in 2002, and previously updated in 2013. To assess whether splenectomy (total or partial), to prevent acute splenic sequestration crises in people with sickle cell disease, improved survival and decreased morbidity in people with sickle cell disease, as compared with regular blood transfusions. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and handsearching relevant journals and abstract books of conference proceedings.Additional trials were sought from the reference lists of the trials and reviews identified by the search strategy.Date of the most recent search: 10 June 2015. All randomized or quasi-randomized controlled trials comparing splenectomy (total or partial) to prevent recurrence of acute splenic sequestration crises with no treatment or blood transfusions in people with sickle cell disease. No trials of splenectomy for acute splenic sequestration were found. No trials of splenectomy for acute splenic sequestration were found. Splenectomy, if full, will prevent further sequestration and if partial, may reduce the recurrence of acute splenic sequestration crises. However, there is a lack of evidence from trials showing that splenectomy improves survival and decreases morbidity in people with sickle cell disease. There is a need for a well-designed, adequately-powered, randomized controlled trial to assess the benefits and risks of splenectomy compared to transfusion programmes, as a means of improving survival and decreasing mortality from acute splenic

  12. Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

    Science.gov (United States)

    Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

    2014-09-01

    The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The United States Department of Energy's Regional Carbon Sequestration Partnerships Program Validation Phase

    Energy Technology Data Exchange (ETDEWEB)

    Litynski, J.T.; Plasynski, S.; McIlvried, H.G.; Mahoney, C.; Srivastava, R.D. [US DOE, Morgantown, WV (United States). National Energy Technology Laboratory

    2008-01-15

    This paper reviews the Validation Phase (Phase II) of the Department of Energy's Regional Carbon Sequestration Partnerships initiative. During the Validation Phase, the seven regional partnerships will put the knowledge learned during the Characterization Phase into practice through field tests that will validate carbon sequestration technologies that are best suited to their respective regions of the country. These tests will verify technologies developed through DOE's core R&D effort and enable implementation of CO{sub 2} sequestration on a large scale, should that become necessary. Pilot projects will have a site-specific focus to test technology; assess formation storage capacity and injectivity; validate and refine existing CO{sub 2} formation models used to determine the transport and fate of CO{sub 2} in the formation; demonstrate the integrity of geologic seals to contain CO{sub 2}; validate monitoring, mitigation, and verification (MMV) technologies; define project costs and compare costs of alternatives; assess potential operational and long-term storage risks; address regulatory requirements; and engage and evaluate public acceptance of sequestration technologies. Field validation tests involving both sequestration in geologic formations and terrestrial sequestration are being developed. The results from the Validation Phase will help to confirm the estimates made during the Characterization Phase and will be used to update the regional atlases and NatCarb.

  14. Carbon sequestration by fruit trees--Chinese apple orchards as an example.

    Science.gov (United States)

    Wu, Ting; Wang, Yi; Yu, Changjiang; Chiarawipa, Rawee; Zhang, Xinzhong; Han, Zhenhai; Wu, Lianhai

    2012-01-01

    Apple production systems are an important component in the Chinese agricultural sector with 1.99 million ha plantation. The orchards in China could play an important role in the carbon (C) cycle of terrestrial ecosystems and contribute to C sequestration. The carbon sequestration capability in apple orchards was analyzed through identifying a set of potential assessment factors and their weighting factors determined by a field model study and literature. The dynamics of the net C sink in apple orchards in China was estimated based on the apple orchard inventory data from 1990s and the capability analysis. The field study showed that the trees reached the peak of C sequestration capability when they were 18 years old, and then the capability began to decline with age. Carbon emission derived from management practices would not be compensated through C storage in apple trees before reaching the mature stage. The net C sink in apple orchards in China ranged from 14 to 32 Tg C, and C storage in biomass from 230 to 475 Tg C between 1990 and 2010. The estimated net C sequestration in Chinese apple orchards from 1990 to 2010 was equal to 4.5% of the total net C sink in the terrestrial ecosystems in China. Therefore, apple production systems can be potentially considered as C sinks excluding the energy associated with fruit production in addition to provide fruits.

  15. Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration

    International Nuclear Information System (INIS)

    Osawa, Hiroyuki; Ohnishi, Hirohide; Takano, Koji; Noguti, Takasi; Mashima, Hirosato; Hoshino, Hiroko; Kita, Hiroto; Sato, Kiichi; Matsui, Hirofumi; Sugano, Kentaro

    2006-01-01

    Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca 2+ ] i ). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca 2+ ] i , activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system

  16. Marine sequestration of carbon in bacterial metabolites.

    Science.gov (United States)

    Lechtenfeld, Oliver J; Hertkorn, Norbert; Shen, Yuan; Witt, Matthias; Benner, Ronald

    2015-03-31

    Linking microbial metabolomics and carbon sequestration in the ocean via refractory organic molecules has been hampered by the chemical complexity of dissolved organic matter (DOM). Here, using bioassay experiments and ultra-high resolution metabolic profiling, we demonstrate that marine bacteria rapidly utilize simple organic molecules and produce exometabolites of remarkable molecular and structural diversity. Bacterial DOM is similar in chemical composition and structural complexity to naturally occurring DOM in sea water. An appreciable fraction of bacterial DOM has molecular and structural properties that are consistent with those of refractory molecules in the ocean, indicating a dominant role for bacteria in shaping the refractory nature of marine DOM. The rapid production of chemically complex and persistent molecules from simple biochemicals demonstrates a positive feedback between primary production and refractory DOM formation. It appears that carbon sequestration in diverse and structurally complex dissolved molecules that persist in the environment is largely driven by bacteria.

  17. Sequestration of plant secondary metabolites by insect herbivores: molecular mechanisms and ecological consequences.

    Science.gov (United States)

    Erb, Matthias; Robert, Christelle Am

    2016-04-01

    Numerous insect herbivores can take up and store plant toxins as self-defense against their own natural enemies. Plant toxin sequestration is tightly linked with tolerance strategies that keep the toxins functional. Specific transporters have been identified that likely allow the herbivore to control the spatiotemporal dynamics of toxin accumulation. Certain herbivores furthermore possess specific enzymes to boost the bioactivity of the sequestered toxins. Ecologists have studied plant toxin sequestration for decades. The recently uncovered molecular mechanisms in combination with transient, non-transgenic systems to manipulate insect gene expression will help to understand the importance of toxin sequestration for food-web dynamics in nature. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Peatland geoengineering: an alternative approach to terrestrial carbon sequestration.

    Science.gov (United States)

    Freeman, Christopher; Fenner, Nathalie; Shirsat, Anil H

    2012-09-13

    Terrestrial and oceanic ecosystems contribute almost equally to the sequestration of ca 50 per cent of anthropogenic CO(2) emissions, and already play a role in minimizing our impact on Earth's climate. On land, the majority of the sequestered carbon enters soil carbon stores. Almost one-third of that soil carbon can be found in peatlands, an area covering just 2-3% of the Earth's landmass. Peatlands are thus well established as powerful agents of carbon capture and storage; the preservation of archaeological artefacts, such as ancient bog bodies, further attest to their exceptional preservative properties. Peatlands have higher carbon storage densities per unit ecosystem area than either the oceans or dry terrestrial systems. However, despite attempts over a number of years at enhancing carbon capture in the oceans or in land-based afforestation schemes, no attempt has yet been made to optimize peatland carbon storage capacity or even to harness peatlands to store externally captured carbon. Recent studies suggest that peatland carbon sequestration is due to the inhibitory effects of phenolic compounds that create an 'enzymic latch' on decomposition. Here, we propose to harness that mechanism in a series of peatland geoengineering strategies whereby molecular, biogeochemical, agronomical and afforestation approaches increase carbon capture and long-term sequestration in peat-forming terrestrial ecosystems.

  19. Ligands in PSI structures

    International Nuclear Information System (INIS)

    Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

    2010-01-01

    A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

  20. Carbon sequestration in wood and paper products

    Science.gov (United States)

    Kenneth E. Skog; Geraldine A. Nicholson

    2000-01-01

    Recognition that increasing levels of CO2 in the atmosphere will affect the global climate has spurred research into reduction global carbon emissions and increasing carbon sequestration. The main nonhuman sources of atmospheric CO2 are animal respiration and decay of biomass. However, increases in atmospheric levels are...

  1. Soil carbon sequestration is a climate stabilization wedge: comments on Sommer and Bossio (2014).

    Science.gov (United States)

    Lassaletta, Luis; Aguilera, Eduardo

    2015-04-15

    Sommer and Bossio (2014) model the potential soil organic carbon (SOC) sequestration in agricultural soils (croplands and grasslands) during the next 87 years, concluding that this process cannot be considered as a climate stabilization wedge. We argue, however, that the amounts of SOC potentially sequestered in both scenarios (pessimistic and optimistic) fulfil the requirements for being considered as wedge because in both cases at least 25 GtC would be sequestered during the next 50 years. We consider that it is precisely in the near future, and meanwhile other solutions are developed, when this stabilization effort is most urgent even if after some decades the sequestration rate is significantly reduced. Indirect effects of SOC sequestration on mitigation could reinforce the potential of this solution. We conclude that the sequestration of organic carbon in agricultural soils as a climate change mitigation tool still deserves important attention for scientists, managers and policy makers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Geologic CO2 Sequestration: Predicting and Confirming Performance in Oil Reservoirs and Saline Aquifers

    Science.gov (United States)

    Johnson, J. W.; Nitao, J. J.; Newmark, R. L.; Kirkendall, B. A.; Nimz, G. J.; Knauss, K. G.; Ziagos, J. P.

    2002-05-01

    Reducing anthropogenic CO2 emissions ranks high among the grand scientific challenges of this century. In the near-term, significant reductions can only be achieved through innovative sequestration strategies that prevent atmospheric release of large-scale CO2 waste streams. Among such strategies, injection into confined geologic formations represents arguably the most promising alternative; and among potential geologic storage sites, oil reservoirs and saline aquifers represent the most attractive targets. Oil reservoirs offer a unique "win-win" approach because CO2 flooding is an effective technique of enhanced oil recovery (EOR), while saline aquifers offer immense storage capacity and widespread distribution. Although CO2-flood EOR has been widely used in the Permian Basin and elsewhere since the 1980s, the oil industry has just recently become concerned with the significant fraction of injected CO2 that eludes recycling and is therefore sequestered. This "lost" CO2 now has potential economic value in the growing emissions credit market; hence, the industry's emerging interest in recasting CO2 floods as co-optimized EOR/sequestration projects. The world's first saline aquifer storage project was also catalyzed in part by economics: Norway's newly imposed atmospheric emissions tax, which spurred development of Statoil's unique North Sea Sleipner facility in 1996. Successful implementation of geologic sequestration projects hinges on development of advanced predictive models and a diverse set of remote sensing, in situ sampling, and experimental techniques. The models are needed to design and forecast long-term sequestration performance; the monitoring techniques are required to confirm and refine model predictions and to ensure compliance with environmental regulations. We have developed a unique reactive transport modeling capability for predicting sequestration performance in saline aquifers, and used it to simulate CO2 injection at Sleipner; we are now

  3. Ecosystem Controls on C & N Sequestration Following Afforestation of Agricultural Lands

    Energy Technology Data Exchange (ETDEWEB)

    E.A. Paul, S.J. Morris, R.T. Conant

    2013-03-05

    In our project, we proposed to continue analysis of our available soil samples and data, and to develop new studies to answer the following objectives: Objective 1) Broaden field based studies of ecosystem C and N compartments to enhance current understanding of C and N sequestration and dynamics. Objective 2) Improve our understanding of mechanism controlling C and N stabilization and dynamics. Objective 3) Investigate the interrelated role of soil temperature and organism type and activity as controlling mechanism in SOC dynamics and sequestration.

  4. Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

    Directory of Open Access Journals (Sweden)

    Tino Wolter

    Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

  5. A case of intralobar pulmonary sequestration

    International Nuclear Information System (INIS)

    Misawa, Takuo; Hongo, Minoru; Okubo, Shinichi; Yamada, Hiroyoshi; Matsuoka, Ken; Soga, Naoko; Kono, Jun; Kusama, Shozo

    1985-01-01

    A 57-year-old female was admitted to our hospital, complaining of hemoptysis. On auscultation, moist rales were audible at the lower portion of left posterior chest. Plain chest roentgenogram showed a round shadow in the left lower lung field. Computed tomography with contrast enhancement revealed an abnormal structure which was contiguous to a strand structure. Dynamic scanning demonstrated opacification of the strand structure and that of the greater part of the abnormal structure during peak opacification of the descending aorta. A part of the abnormal structure was opacified during the same phase as the opacification of the right ventricle and pulmonary artery. A diagnosis of intralobar pulmonary sequestration associated with pulmonary arterio-venous malformation was confirmed by thoracic aortography and left pulmonary arteriography. The hemoptysis was found to be caused by chronic bronchitis. It was emphasized that dynamic computed tomography is very useful to diagnose intralobar pulmonary sequestration and to assess the presence of pulmonary arterio-venous malformation. In addition, it is of particular interest that this case cannot be assigned to any category of Pryce's classification although it resembles both type I and IV. (author)

  6. Identification and Characterization of KCASH2 and KCASH3, 2 Novel Cullin3 Adaptors Suppressing Histone Deacetylase and Hedgehog Activity in Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2011-04-01

    Full Text Available Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent a potential therapeutic target for Hh-dependent tumors, but still little information is available on the physiological mechanisms of HDAC regulation. The putative tumor suppressor RENKCTD11 acts through ubiquitination-dependent degradation of HDAC1, thereby affecting Hh activity and medulloblastoma growth. We identify and characterize here two RENKCTD11 homologues, defining a new family of proteins named KCASH, as “KCTD containing, Cullin3 adaptor, suppressor of Hedgehog.” Indeed, the novel genes (KCASH2KCTD21 and KCASH3KCTD6 share with RENKCTD11 a number of features, such as a BTB domain required for the formation of a Cullin3 ubiquitin ligase complex and HDAC1 ubiquitination and degradation capability, suppressing the acetylation-dependent Hh/Gli signaling. Expression of KCASH2 and -3 is observed in cerebellum, whereas epigenetic silencing and allelic deletion are observed in human medulloblastoma. Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis. Accordingly, they might represent a promising class of endogenous “agents” through which this pathway may be targeted.

  7. [Regional and global estimates of carbon stocks and carbon sequestration capacity in forest ecosystems: A review].

    Science.gov (United States)

    Liu, Wei-wei; Wang, Xiao-ke; Lu, Fei; Ouyang, Zhi-yun

    2015-09-01

    As a dominant part of terrestrial ecosystems, forest ecosystem plays an important role in absorbing atmospheric CO2 and global climate change mitigation. From the aspects of zonal climate and geographical distribution, the present carbon stocks and carbon sequestration capacity of forest ecosystem were comprehensively examined based on the review of the latest literatures. The influences of land use change on forest carbon sequestration were analyzed, and factors that leading to the uncertainty of carbon sequestration assessment in forest ecosystem were also discussed. It was estimated that the current forest carbon stock was in the range of 652 to 927 Pg C and the carbon sequestration capacity was approximately 4.02 Pg C · a(-1). In terms of zonal climate, the carbon stock and carbon sequestration capacity of tropical forest were the maximum, about 471 Pg C and 1.02-1.3 Pg C · a(-1) respectively; then the carbon stock of boreal forest was about 272 Pg C, while its carbon sequestration capacity was the minimum, approximately 0.5 Pg C · a(-1); for temperate forest, the carbon stock was minimal, around 113 to 159 Pg C and its carbon sequestration capacity was 0.8 Pg C · a(-1). From the aspect of geographical distribution, the carbon stock of forest ecosystem in South America was the largest (187.7-290 Pg C), then followed by European (162.6 Pg C), North America (106.7 Pg C), Africa (98.2 Pg C) and Asia (74.5 Pg C), and Oceania (21.7 Pg C). In addition, carbon sequestration capacity of regional forest ecosystem was summed up as listed below: Tropical South America forest was the maximum (1276 Tg C · a(-1)), then were Tropical Africa (753 Tg C · a(-1)), North America (248 Tg C · a(-1)) and European (239 Tg C · a(-1)), and East Asia (98.8-136.5 Tg C · a(-1)) was minimum. To further reduce the uncertainty in the estimations of the carbon stock and carbon sequestration capacity of forest ecosystem, comprehensive application of long-term observation, inventories

  8. Hedgehog signaling: endocrine gland development and function.

    Science.gov (United States)

    Cohen, M Michael

    2010-01-01

    The role of hedgehog signaling is analyzed in relation to the developing endocrine glands: pituitary, ovary, testis, adrenal cortex, pancreas, prostate, and epiphyseal growth. Experimental and pathological correlates of these organs are also discussed. The second section addresses a number of topics. First, the pituitary gland, no matter how hypoplastic, is present in most cases of human holoprosencephaly, unlike animals in which it is always said to be absent. The difference appears to be that animal mutations and teratogenic models involve both copies of the gene in question, whereas in humans the condition is most commonly heterozygous. Second, tests of endocrine function are not reported with great frequency, and an early demise in severe cases of holoprosencephaly accounts for this trend. Reported tests of endocrine function are reviewed. Third, diabetes insipidus has been recorded in a number of cases of holoprosencephaly. Its frequency is unknown because it could be masked by adrenal insufficiency in some cases and may not be recognized in others. Because of the abnormal hypothalamic-infundibular region in holoprosencephaly, diabetes insipidus could be caused by a defect in the supra-optic or paraventricular hypothalamic nuclei or in release of ADH via the infundibulum and posterior pituitary.

  9. Regulator of G-protein signaling - 5 (RGS5 is a novel repressor of hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    William M Mahoney

    Full Text Available Hedgehog (Hh signaling plays fundamental roles in morphogenesis, tissue repair, and human disease. Initiation of Hh signaling is controlled by the interaction of two multipass membrane proteins, patched (Ptc and smoothened (Smo. Recent studies identify Smo as a G-protein coupled receptor (GPCR-like protein that signals through large G-protein complexes which contain the Gαi subunit. We hypothesize Regulator of G-Protein Signaling (RGS proteins, and specifically RGS5, are endogenous repressors of Hh signaling via their ability to act as GTPase activating proteins (GAPs for GTP-bound Gαi, downstream of Smo. In support of this hypothesis, we demonstrate that RGS5 over-expression inhibits sonic hedgehog (Shh-mediated signaling and osteogenesis in C3H10T1/2 cells. Conversely, signaling is potentiated by siRNA-mediated knock-down of RGS5 expression, but not RGS4 expression. Furthermore, using immuohistochemical analysis and co-immunoprecipitation (Co-IP, we demonstrate that RGS5 is present with Smo in primary cilia. This organelle is required for canonical Hh signaling in mammalian cells, and RGS5 is found in a physical complex with Smo in these cells. We therefore conclude that RGS5 is an endogenous regulator of Hh-mediated signaling and that RGS proteins are potential targets for novel therapeutics in Hh-mediated diseases.

  10. Black-holes-hedgehogs in the false vacuum and a new physics beyond the Standard Model

    Science.gov (United States)

    Das, C. R.; Laperashvili, L. V.; Sidharth, B. G.; Nielsen, H. B.

    2017-12-01

    In the present talk, we consider the existence of the two degenerate universal vacua: a) the first Electroweak vacuum at v = 246 GeV - “true vacuum”, and b) the second Planck scale “false vacuum” at v 2 ∼ 1018 GeV. In these vacua, we investigated the different topological defects. The main aim of this paper is an investigation of the hedgehog’s configurations as defects of the false vacuum. In the framework of the f(R) gravity, suggested by authors in their Gravi-Weak Unification model, we obtained a black hole solution, which corresponds to a “hedgehog” - global monopole, “swallowed” by a black-hole with mass ∼ 1019 GeV. These black-holes form a lattice-like structure of the vacuum at the Planck scale. Considering the results of the hedgehog lattice theory in the framework of the SU(2) Yang-Mills gauge-invariant theory with hedgehogs in the Wilson loops, we have used the critical value of temperature for the hedgehog’s confinement phase. This result gave us the possibility to conclude that there exist triplet Higgs fields which can contribute to the SM at the energy scale ≃ 104 ∼ 105 GeV. Showing a new physics at the scale 10÷100 TeV, these triplet Higgs particles can provide the stability of the EW-vacuum of the SM.

  11. Forest management and carbon sequestration in the Mediterranean region: A review

    International Nuclear Information System (INIS)

    Ruiz-Peinado, R.; Bravo-Oviedo, A.; López-Senespleda, E.; Bravo, F.; Río, M. Del

    2017-01-01

    Aim of the study: To review and acknowledge the value of carbon sequestration by forest management in the Mediterranean area. Material and methods: We review the main effects of forest management by comparing the effects of silviculture systems (even-aged vs. uneven-aged stands, coppice systems, agroforestry systems), silvicultural options (thinning, rotation period, species composition), afforestation, harvesting, fire impact or effects of shrub layer on carbon sequestration in the Mediterranean area. Main results: We illustrate as forest management can clearly improve forest carbon sequestration amounts. We conclude that forest management is an effective way to maintain and enhance high carbon sequestration rates in order to cope with climate change and provision of ecosystem services. We also think that although much effort has been put into this topic research, there are still certain gaps that must be dealt with to increase our scientific knowledge and in turn transfer this knowledge to forest practitioners in order to achieve sustainable management aimed at mitigating climate change. Research highlights: It is important to underline the importance of forests in the carbon cycle as this role can be enhanced by forest managers through sustainable forest management. The effects of different management options or disturbances can be critical as regards mitigating climate change. Understanding the effects of forest management is even more important in the Mediterranean area, given that the current high climatic variability together with historical human exploitation and disturbance events make this area more vulnerable to the effects of climate change

  12. Forest management and carbon sequestration in the Mediterranean region: A review

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz-Peinado, R.; Bravo-Oviedo, A.; López-Senespleda, E.; Bravo, F.; Río, M. Del

    2017-11-01

    Aim of the study: To review and acknowledge the value of carbon sequestration by forest management in the Mediterranean area. Material and methods: We review the main effects of forest management by comparing the effects of silviculture systems (even-aged vs. uneven-aged stands, coppice systems, agroforestry systems), silvicultural options (thinning, rotation period, species composition), afforestation, harvesting, fire impact or effects of shrub layer on carbon sequestration in the Mediterranean area. Main results: We illustrate as forest management can clearly improve forest carbon sequestration amounts. We conclude that forest management is an effective way to maintain and enhance high carbon sequestration rates in order to cope with climate change and provision of ecosystem services. We also think that although much effort has been put into this topic research, there are still certain gaps that must be dealt with to increase our scientific knowledge and in turn transfer this knowledge to forest practitioners in order to achieve sustainable management aimed at mitigating climate change. Research highlights: It is important to underline the importance of forests in the carbon cycle as this role can be enhanced by forest managers through sustainable forest management. The effects of different management options or disturbances can be critical as regards mitigating climate change. Understanding the effects of forest management is even more important in the Mediterranean area, given that the current high climatic variability together with historical human exploitation and disturbance events make this area more vulnerable to the effects of climate change.

  13. Carbon Sequestration by Fruit Trees - Chinese Apple Orchards as an Example

    Science.gov (United States)

    Wu, Ting; Wang, Yi; Yu, Changjiang; Chiarawipa, Rawee; Zhang, Xinzhong; Han, Zhenhai; Wu, Lianhai

    2012-01-01

    Apple production systems are an important component in the Chinese agricultural sector with 1.99 million ha plantation. The orchards in China could play an important role in the carbon (C) cycle of terrestrial ecosystems and contribute to C sequestration. The carbon sequestration capability in apple orchards was analyzed through identifying a set of potential assessment factors and their weighting factors determined by a field model study and literature. The dynamics of the net C sink in apple orchards in China was estimated based on the apple orchard inventory data from 1990s and the capability analysis. The field study showed that the trees reached the peak of C sequestration capability when they were 18 years old, and then the capability began to decline with age. Carbon emission derived from management practices would not be compensated through C storage in apple trees before reaching the mature stage. The net C sink in apple orchards in China ranged from 14 to 32 Tg C, and C storage in biomass from 230 to 475 Tg C between 1990 and 2010. The estimated net C sequestration in Chinese apple orchards from 1990 to 2010 was equal to 4.5% of the total net C sink in the terrestrial ecosystems in China. Therefore, apple production systems can be potentially considered as C sinks excluding the energy associated with fruit production in addition to provide fruits. PMID:22719974

  14. Carbon sequestration by fruit trees--Chinese apple orchards as an example.

    Directory of Open Access Journals (Sweden)

    Ting Wu

    Full Text Available Apple production systems are an important component in the Chinese agricultural sector with 1.99 million ha plantation. The orchards in China could play an important role in the carbon (C cycle of terrestrial ecosystems and contribute to C sequestration. The carbon sequestration capability in apple orchards was analyzed through identifying a set of potential assessment factors and their weighting factors determined by a field model study and literature. The dynamics of the net C sink in apple orchards in China was estimated based on the apple orchard inventory data from 1990s and the capability analysis. The field study showed that the trees reached the peak of C sequestration capability when they were 18 years old, and then the capability began to decline with age. Carbon emission derived from management practices would not be compensated through C storage in apple trees before reaching the mature stage. The net C sink in apple orchards in China ranged from 14 to 32 Tg C, and C storage in biomass from 230 to 475 Tg C between 1990 and 2010. The estimated net C sequestration in Chinese apple orchards from 1990 to 2010 was equal to 4.5% of the total net C sink in the terrestrial ecosystems in China. Therefore, apple production systems can be potentially considered as C sinks excluding the energy associated with fruit production in addition to provide fruits.

  15. Intralobar pulmonary sequestration: a case report

    International Nuclear Information System (INIS)

    Nacif, Marcelo Souto; Miranda, Bruno Jose de Pinho; Caramel, Juliana Mauro; Jauregui, Gustavo Federico; Santos, Alair Augusto Sarmet Moreira Damas dos

    2001-01-01

    We report the case of a 49-year-old patient with repeated lung infections. Chest x-rays showed a mass in the posterior basal segment of the right lung. Angio tomography and 3D reconstructions showed a blood supply coming from the descending aorta. The analysis of the surgical specimen confirmed the occurrence of intra lobar pulmonary sequestration with a cavitation filled with mucus. (author)

  16. Mycorrhizae Alter Toxin Sequestration and Performance of Two Specialist Herbivores

    Directory of Open Access Journals (Sweden)

    Amanda R. Meier

    2018-04-01

    Full Text Available Multitrophic species interactions are shaped by both top-down and bottom-up factors. Belowground symbionts of plants, such as arbuscular mycorrhizal fungi (AMF, can alter the strength of these forces by altering plant phenotype. For example, AMF-mediated changes in foliar toxin and nutrient concentrations may influence herbivore growth and fecundity. In addition, many specialist herbivores sequester toxins from their host plants to resist natural enemies, and the extent of sequestration varies with host plant secondary chemistry. Therefore, by altering plant phenotype, AMF may affect both herbivore performance and their resistance to natural enemies. We examined how inoculation of plants with AMF influences toxin sequestration and performance of two specialist herbivores feeding upon four milkweed species (Asclepias incarnata, A. curassavica, A. latifolia, A. syriaca. We raised aphids (Aphis nerii and caterpillars (Danaus plexippus on plants for 6 days in a fully factorial manipulation of milkweed species and level of AMF inoculation (zero, medium, and high. We then assessed aphid and caterpillar sequestration of toxins (cardenolides and performance, and measured defensive and nutritive traits of control plants. Aphids and caterpillars sequestered higher concentrations of cardenolides from plants inoculated with AMF across all milkweed species. Aphid per capita growth rates and aphid body mass varied non-linearly with increasing AMF inoculum availability; across all milkweed species, aphids had the lowest performance under medium levels of AMF availability and highest performance under high AMF availability. In contrast, caterpillar survival varied strongly with AMF availability in a plant species-specific manner, and caterpillar growth was unaffected by AMF. Inoculation with AMF increased foliar cardenolide concentrations consistently among milkweed species, but altered aboveground biomasses and foliar phosphorous concentrations in a plant

  17. Southwest Regional Partnership on Carbon Sequestration Phase II

    Energy Technology Data Exchange (ETDEWEB)

    James Rutledge

    2011-02-01

    The Southwest Regional Partnership (SWP) on Carbon Sequestration designed and deployed a medium-scale field pilot test of geologic carbon dioxide (CO2) sequestration in the Aneth oil field. Greater Aneth oil field, Utah's largest oil producer, was discovered in 1956 and has produced over 455 million barrels of oil (72 million m3). Located in the Paradox Basin of southeastern Utah, Greater Aneth is a stratigraphic trap producing from the Pennsylvanian Paradox Formation. Because it represents an archetype oil field of the western U.S., Greater Aneth was selected as one of three geologic pilots to demonstrate combined enhanced oil recovery (EOR) and CO2 sequestration under the auspices of the SWP on Carbon Sequestration, sponsored by the U.S. Department of Energy. The pilot demonstration focuced on the western portion of the Aneth Unit as this area of the field was converted from waterflood production to CO2 EOR starting in late 2007. The Aneth Unit is in the northwestern part of the field and has produced 149 million barrels (24 million m3) of the estimated 450 million barrels (71.5 million m3) of the original oil in place - a 33% recovery rate. The large amount of remaining oil makes the Aneth Unit ideal to demonstrate both CO2 storage capacity and EOR by CO2 flooding. This report summarizes the geologic characterization research, the various field monitoring tests, and the development of a geologic model and numerical simulations conducted for the Aneth demonstration project. The Utah Geological Survey (UGS), with contributions from other Partners, evaluated how the surface and subsurface geology of the Aneth Unit demonstration site will affect sequestration operations and engineering strategies. The UGS-research for the project are summarized in Chapters 1 through 7, and includes (1) mapping the surface geology including stratigraphy, faulting, fractures, and deformation bands, (2) describing the local Jurassic and Cretaceous stratigraphy, (3) mapping the

  18. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Directory of Open Access Journals (Sweden)

    Stéphanie Pérot

    Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

  19. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    Science.gov (United States)

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

  20. Subcellular Localization of Patched and Smoothened, the Receptors for Sonic Hedgehog Signaling, in the Hippocampal Neuron

    OpenAIRE

    Petralia, Ronald S.; Schwartz, Catherine M.; Wang, Ya-Xian; Mattson, Mark P.; Yao, Pamela J.

    2011-01-01

    Cumulative evidence suggests that, aside from patterning the embryonic neural tube, Sonic hedgehog (Shh) signaling plays important roles in the mature nervous system. In this study, we investigate the expression and localization of the Shh signaling receptors, Patched (Ptch) and Smoothened (Smo), in the hippocampal neurons of young and mature rats. Reverse transcriptase-polymerase chain reaction and immunoblotting analyses show that the expression of Ptch and Smo remains at a moderate level i...

  1. Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

    Science.gov (United States)

    Milowska, Karolina Z; Stolarczyk, Jacek K

    2016-05-14

    The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

  2. Calcium silicates synthesised from industrial residues with the ability for CO2 sequestration.

    Science.gov (United States)

    Morales-Flórez, Victor; Santos, Alberto; López, Antonio; Moriña, Isabel; Esquivias, Luis

    2014-12-01

    This work explored several synthesis routes to obtain calcium silicates from different calcium-rich and silica-rich industrial residues. Larnite, wollastonite and calcium silicate chloride were successfully synthesised with moderate heat treatments below standard temperatures. These procedures help to not only conserve natural resources, but also to reduce the energy requirements and CO2 emissions. In addition, these silicates have been successfully tested as carbon dioxide sequesters, to enhance the viability of CO2 mineral sequestration technologies using calcium-rich industrial by-products as sequestration agents. Two different carbon sequestration experiments were performed under ambient conditions. Static experiments revealed carbonation efficiencies close to 100% and real-time resolved experiments characterised the dynamic behaviour and ability of these samples to reduce the CO2 concentration within a mixture of gases. The CO2 concentration was reduced up to 70%, with a carbon fixation dynamic ratio of 3.2 mg CO2 per g of sequestration agent and minute. Our results confirm the suitability of the proposed synthesis routes to synthesise different calcium silicates recycling industrial residues, being therefore energetically more efficient and environmentally friendly procedures for the cement industry. © The Author(s) 2014.

  3. Design of a Bioactive Small Molecule that Targets the Myotonic Dystrophy Type 1 RNA Via an RNA Motif-Ligand Database & Chemical Similarity Searching

    Science.gov (United States)

    Parkesh, Raman; Childs-Disney, Jessica L.; Nakamori, Masayuki; Kumar, Amit; Wang, Eric; Wang, Thomas; Hoskins, Jason; Tran, Tuan; Housman, David; Thornton, Charles A.; Disney, Matthew D.

    2012-01-01

    Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5′CUG/3′GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, Sarco(endo)plasmic reticulum Ca2+ ATPase 1 (Serca1/Atp2a1), and cardiac troponin T (cTNT). Based on these observations, the development of small molecule ligands that target specifically expanded DM1 repeats could serve as therapeutics. In the present study, computational screening was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of inhibitors of the RNA-protein complex with low micromolar IC50’s, which are >20-fold more potent than the query compounds, were identified. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with virtual screening. PMID:22300544

  4. Sonic hedgehog signaling inhibition provides opportunities for targeted therapy by sulforaphane in regulating pancreatic cancer stem cell self-renewal.

    Directory of Open Access Journals (Sweden)

    Mariana Rodova

    Full Text Available Dysregulation of the sonic hedgehog (Shh signaling pathway has been associated with cancer stem cells (CSC and implicated in the initiation of pancreatic cancer. Pancreatic CSCs are rare tumor cells characterized by their ability to self-renew, and are responsible for tumor recurrence accompanied by resistance to current therapies. The lethality of these incurable, aggressive and invasive pancreatic tumors remains a daunting clinical challenge. Thus, the objective of this study was to investigate the role of Shh pathway in pancreatic cancer and to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables, inhibits self-renewal capacity of human pancreatic CSCs. Interestingly, we demonstrate here that Shh pathway is highly activated in pancreatic CSCs and plays important role in maintaining stemness by regulating the expression of stemness genes. Given the requirement for Hedgehog in pancreatic cancer, we investigated whether hedgehog blockade by SFN could target the stem cell population in pancreatic cancer. In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN, suggesting the clonogenic depletion of the CSCs. Interestingly, SFN inhibited the components of Shh pathway and Gli transcriptional activity. Interference of Shh-Gli signaling significantly blocked SFN-induced inhibitory effects demonstrating the requirement of an active pathway for the growth of pancreatic CSCs. SFN also inhibited downstream targets of Gli transcription by suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4 as well as PDGFRα and Cyclin D1. Furthermore, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases. Our data reveal the essential role of Shh-Gli signaling in controlling the characteristics of pancreatic CSCs. We propose that pancreatic cancer preventative effects of SFN may result from inhibition of the Shh pathway

  5. Hedgehog signaling activation induces stem cell proliferation and hormone release in the adult pituitary gland

    OpenAIRE

    Joanna Pyczek; Rolf Buslei; David Schult; Annett Hölsken; Michael Buchfelder; Ina Heß; Heidi Hahn; Anja Uhmann

    2016-01-01

    Hedgehog (HH) signaling is known to be essential during the embryonal development of the pituitary gland but the knowledge about its role in the adult pituitary and in associated tumors is sparse. In this report we investigated the effect of excess Hh signaling activation in murine pituitary explants and analyzed the HH signaling status of human adenopituitary lobes and a large cohort of pituitary adenomas. Our data show that excess Hh signaling led to increased proliferation of Sox2(+) and S...

  6. [Effect of hedgehog hydnum on the delay of fatigue in mice].

    Science.gov (United States)

    Lu, Y H; Xin, C L; Zhou, Y F; Liu, X W; Chi, J W; Chang, X

    1996-02-01

    Two groups of mice were fed with either hedgehog hydnum powder or extract for sixty days. For the assay of fatigue, the activity of serum lactate dehydrogenase, the serum urea nitrogen content, blood lactic acid, hepatic and muscular glycogen, and the physical stamina of the mice were determined. The activity of serum lactate dehydrogenase and the hepatic and muscular glycogen content in the experimental mice were evidently higher than that in the control mice (P increase in blood lactic acid and serum urea nitrogen in the experimental mice was significantly lower than that in the control mice (P stamina swimming, the experimental mice drowned after a longer period of time than the control mice (P stamina and delaying fatigue in mice.

  7. The hedgehog pathway gene shifted functions together with the hmgcr-dependent isoprenoid biosynthetic pathway to orchestrate germ cell migration.

    Directory of Open Access Journals (Sweden)

    Girish Deshpande

    Full Text Available The Drosophila embryonic gonad is assembled from two distinct cell types, the Primordial Germ Cells (PGCs and the Somatic Gonadal Precursor cells (SGPs. The PGCs form at the posterior of blastoderm stage embryos and are subsequently carried inside the embryo during gastrulation. To reach the SGPs, the PGCs must traverse the midgut wall and then migrate through the mesoderm. A combination of local repulsive cues and attractive signals emanating from the SGPs guide migration. We have investigated the role of the hedgehog (hh pathway gene shifted (shf in directing PGC migration. shf encodes a secreted protein that facilitates the long distance transmission of Hh through the proteoglycan matrix after it is released from basolateral membranes of Hh expressing cells in the wing imaginal disc. shf is expressed in the gonadal mesoderm, and loss- and gain-of-function experiments demonstrate that it is required for PGC migration. Previous studies have established that the hmgcr-dependent isoprenoid biosynthetic pathway plays a pivotal role in generating the PGC attractant both by the SGPs and by other tissues when hmgcr is ectopically expressed. We show that production of this PGC attractant depends upon shf as well as a second hh pathway gene gγ1. Further linking the PGC attractant to Hh, we present evidence indicating that ectopic expression of hmgcr in the nervous system promotes the release/transmission of the Hh ligand from these cells into and through the underlying mesodermal cell layer, where Hh can contact migrating PGCs. Finally, potentiation of Hh by hmgcr appears to depend upon cholesterol modification.

  8. Balancing Methane Emissions and Carbon Sequestration in Tropical/Subtropical Coastal Wetlands: A Review

    Science.gov (United States)

    Mitsch, W. J.; Schafer, K. V.; Cabezas, A.; Bernal, B.

    2016-02-01

    Wetlands are estimated to emit about 20 to 25 percent of current global CH4 emissions, or about 120 to 180 Tg-CH4 yr-1. Thus, in climate change discussions concerning wetlands, these "natural emissions" often receive the most attention, often overshadowing the more important ecosystem services that wetlands provide, including carbon sequestration. While methane emissions from coastal wetlands have generally been described as small due to competing biogeochemical cycles, disturbance of coastal wetlands, e.g., the introduction of excessive freshwater fluxes or substrate disturbance, can lead to much higher methane emission rates. Carbon sequestration is a more positive carbon story about wetlands and coastal wetlands in particular. The rates of carbon sequestration in tropical/subtropical coastal wetlands, mainly mangroves, are in the range of 100 to 200 g-C m-2 yr-1, two to ten times higher rates than in the more frequently studied northern peatlands. This function of coastal wetlands has significant international support now for mangrove conservation and it is referred to in the literature and popular press as blue carbon. This presentation will summarize what we know about methane emissions and carbon sequestration in tropical/subtropical coastal wetlands, how these rates compare with those in non-tropical and/or inland wetlands, and a demonstration of two or three models that compare methane fluxes with carbon dioxide sequestration to determine if wetlands are net sinks of radiative forcing. The presentation will also present a global model of carbon with an emphasis on wetlands.

  9. Reaction mechanisms for enhancing carbon dioxide mineral sequestration

    Science.gov (United States)

    Jarvis, Karalee Ann

    Increasing global temperature resulting from the increased release of carbon dioxide into the atmosphere is one of the greatest problems facing society. Nevertheless, coal plants remain the largest source of electrical energy and carbon dioxide gas. For this reason, researchers are searching for methods to reduce carbon dioxide emissions into the atmosphere from the combustion of coal. Mineral sequestration of carbon dioxide reacted in electrolyte solutions at 185°C and 2200 psi with olivine (magnesium silicate) has been shown to produce environmentally benign carbonates. However, to make this method feasible for industrial applications, the reaction rate needs to be increased. Two methods were employed to increase the rate of mineral sequestration: reactant composition and concentration were altered independently in various runs. The products were analyzed with complete combustion for total carbon content. Crystalline phases in the product were analyzed with Debye-Scherrer X-ray powder diffraction. To understand the reaction mechanism, single crystals of San Carlos Olivine were reacted in two solutions: (0.64 M NaHCO3/1 M NaCl) and (5.5 M KHCO3) and analyzed with scanning electron microscopy (SEM), transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), and fluctuation electron microscopy (FEM) to study the surface morphology, atomic crystalline structure, composition and amorphous structure. From solution chemistry studies, it was found that increasing the activity of the bicarbonate ion increased the conversion rate of carbon dioxide to magnesite. The fastest conversion, 60% conversion in one hour, occurred in a solution of 5.5 M KHCO3. The reaction product particles, magnesium carbonate, significantly increased in both number density and size on the coupon when the bicarbonate ion activity was increased. During some experiments reaction vessel corrosion also altered the mineral sequestration mechanism. Nickel ions from vessel

  10. Carbon storage and sequestration by trees in urban and community areas of the United States

    International Nuclear Information System (INIS)

    Nowak, David J.; Greenfield, Eric J.; Hoehn, Robert E.; Lapoint, Elizabeth

    2013-01-01

    Carbon storage and sequestration by urban trees in the United States was quantified to assess the magnitude and role of urban forests in relation to climate change. Urban tree field data from 28 cities and 6 states were used to determine the average carbon density per unit of tree cover. These data were applied to statewide urban tree cover measurements to determine total urban forest carbon storage and annual sequestration by state and nationally. Urban whole tree carbon storage densities average 7.69 kg C m −2 of tree cover and sequestration densities average 0.28 kg C m −2 of tree cover per year. Total tree carbon storage in U.S. urban areas (c. 2005) is estimated at 643 million tonnes ($50.5 billion value; 95% CI = 597 million and 690 million tonnes) and annual sequestration is estimated at 25.6 million tonnes ($2.0 billion value; 95% CI = 23.7 million to 27.4 million tonnes). -- Highlights: •Total tree carbon storage in U.S. urban areas (c. 2005) is estimated at 643 million tonnes. •Total tree carbon storage in U.S. urban and community areas is estimated at 1.36 billion tonnes. •Net carbon sequestration in U.S. urban areas varies by state and is estimated at 18.9 million tonnes per year. •Overlap between U.S. forest and urban forest carbon estimates is between 247 million and 303 million tonnes. -- Field and tree cover measurements reveal carbon storage and sequestration by trees in U.S. urban and community areas

  11. Carbon sequestration index as a determinant for climate change mitigation: Case study of Bintan Island

    Science.gov (United States)

    Wahyudi, A.'an J.; Afdal; Prayudha, Bayu; Dharmawan, I. W. E.; Irawan, Andri; Abimanyu, Haznan; Meirinawati, Hanny; Surinati, Dewi; Syukri, Agus F.; Yuliana, Chitra I.; Yuniati, Putri I.

    2018-02-01

    The increase of the anthropogenic carbon dioxide (CO2) affects the global carbon cycle altering the atmospheric system and initiates the climate changes. There are two ways to mitigate these changes, by maintaining the greenhouse gasses below the carbon budget and by conserving the marine and terrestrial vegetation for carbon sequestration. These two strategies become variable to the carbon sequestration index (CSI) that represents the potential of a region in carbon sequestration, according to its natural capacity. As a study case, we conducted carbon sequestration research in Bintan region (Bintan Island and its surrounding), Riau Archipelago province. This research was aimed to assess the CSI and its possibility for climate change mitigation. We observed carbon sequestration of seagrass meadows and mangrove, greenhouse gas (CO2) emission (correlated to population growth, the increase of vehicles), and CSI. Bintan region has 125,849.9 ha of vegetation area and 14,879.6 ha of terrestrial and marine vegetation area, respectively. Both vegetation areas are able to sequester 0.262 Tg C yr-1 in total and marine vegetation contributes about 77.1%. Total CO2 emission in Bintan region is up to 0.273 Tg C yr-1, produced by transportation, industry and land use sectors. Therefore, CSI of the Bintan region is 0.98, which is above the global average (i.e. 0.58). This value demonstrates that the degree of sequestration is comparable to the total carbon emission. This result suggests that Bintan’s vegetation has high potential for reducing greenhouse gas effects.

  12. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

    Directory of Open Access Journals (Sweden)

    Carolina N Perdigoto

    2016-07-01

    Full Text Available An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2 in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

  13. Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

    Science.gov (United States)

    Perdigoto, Carolina N; Dauber, Katherine L; Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J; Cohen, Idan; Santoriello, Francis J; Zhao, Dejian; Zheng, Deyou; Hsu, Ya-Chieh; Ezhkova, Elena

    2016-07-01

    An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

  14. Evolutionary genomics and adaptive evolution of the hedgehog gene family (Shh, Ihh and Dhh) in vertebrates

    DEFF Research Database (Denmark)

    Pereira, Joana; Johnson, Warren E.; O'Brien, Stephen J.

    2014-01-01

    The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typi...

  15. Mesoscale carbon sequestration site screening and CCS infrastructure analysis.

    Science.gov (United States)

    Keating, Gordon N; Middleton, Richard S; Stauffer, Philip H; Viswanathan, Hari S; Letellier, Bruce C; Pasqualini, Donatella; Pawar, Rajesh J; Wolfsberg, Andrew V

    2011-01-01

    We explore carbon capture and sequestration (CCS) at the meso-scale, a level of study between regional carbon accounting and highly detailed reservoir models for individual sites. We develop an approach to CO(2) sequestration site screening for industries or energy development policies that involves identification of appropriate sequestration basin, analysis of geologic formations, definition of surface sites, design of infrastructure, and analysis of CO(2) transport and storage costs. Our case study involves carbon management for potential oil shale development in the Piceance-Uinta Basin, CO and UT. This study uses new capabilities of the CO(2)-PENS model for site screening, including reservoir capacity, injectivity, and cost calculations for simple reservoirs at multiple sites. We couple this with a model of optimized source-sink-network infrastructure (SimCCS) to design pipeline networks and minimize CCS cost for a given industry or region. The CLEAR(uff) dynamical assessment model calculates the CO(2) source term for various oil production levels. Nine sites in a 13,300 km(2) area have the capacity to store 6.5 GtCO(2), corresponding to shale-oil production of 1.3 Mbbl/day for 50 years (about 1/4 of U.S. crude oil production). Our results highlight the complex, nonlinear relationship between the spatial deployment of CCS infrastructure and the oil-shale production rate.

  16. Analysis of CO2 Separation from Flue Gas, Pipeline Transportation, and Sequestration in Coal

    Energy Technology Data Exchange (ETDEWEB)

    Eric P. Robertson

    2007-09-01

    This report was written to satisfy a milestone of the Enhanced Coal Bed Methane Recovery and CO2 Sequestration task of the Big Sky Carbon Sequestration project. The report begins to assess the costs associated with separating the CO2 from flue gas and then injecting it into an unminable coal seam. The technical challenges and costs associated with CO2 separation from flue gas and transportation of the separated CO2 from the point source to an appropriate sequestration target was analyzed. The report includes the selection of a specific coal-fired power plant for the application of CO2 separation technology. An appropriate CO2 separation technology was identified from existing commercial technologies. The report also includes a process design for the chosen technology tailored to the selected power plant that used to obtain accurate costs of separating the CO2 from the flue gas. In addition, an analysis of the costs for compression and transportation of the CO2 from the point-source to an appropriate coal bed sequestration site was included in the report.

  17. An index-based approach to assessing recalcitrance and soil carbon sequestration potential of engineered black carbons (biochars).

    Science.gov (United States)

    Harvey, Omar R; Kuo, Li-Jung; Zimmerman, Andrew R; Louchouarn, Patrick; Amonette, James E; Herbert, Bruce E

    2012-02-07

    The ability of engineered black carbons (or biochars) to resist abiotic and, or biotic degradation (herein referred to as recalcitrance) is crucial to their successful deployment as a soil carbon sequestration strategy. A new recalcitrance index, the R(50), for assessing biochar quality for carbon sequestration is proposed. The R(50) is based on the relative thermal stability of a given biochar to that of graphite and was developed and evaluated with a variety of biochars (n = 59), and soot-like black carbons. Comparison of R(50), with biochar physicochemical properties and biochar-C mineralization revealed the existence of a quantifiable relationship between R(50) and biochar recalcitrance. As presented here, the R(50) is immediately applicable to pre-land application screening of biochars into Class A (R(50) ≥ 0.70), Class B (0.50 ≤ R(50) carbon sequestration classes. Class A and Class C biochars would have carbon sequestration potential comparable to soot/graphite and uncharred plant biomass, respectively, whereas Class B biochars would have intermediate carbon sequestration potential. We believe that the coupling of the R(50), to an index-based degradation, and an economic model could provide a suitable framework in which to comprehensively assess soil carbon sequestration in biochars.

  18. Sonic Hedgehog Signaling in Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Xiulong Xu

    2017-10-01

    Full Text Available Thyroid cancer is the most common malignancy of the endocrine system. The initiation of thyroid cancer is often triggered by a genetic mutation in the phosphortidylinositol-3 kinase (PI3K or mitogen-activated protein kinase (MAPK pathway, such as RAS and BRAF, or by the rearrangement of growth factor receptor tyrosine kinase genes such as RET/PTC. The sonic hedgehog (Shh pathway is evolutionarily conserved and plays an important role in the embryonic development of normal tissues and organs. Gene mutations in the Shh pathway are involved in basal cell carcinomas (BCC. Activation of the Shh pathway due to overexpression of the genes encoding the components of this pathway stimulates the growth and spread of a wide range of cancer types. The Shh pathway also plays an important role in cancer stem cell (CSC self-renewal. GDC-0449 and LDE-225, two inhibitors of this pathway, have been approved for treating BCC and are being tested as a single agent or in combination with other drugs for treating various other cancers. Here, we review the recent findings on activation of the Shh pathway in thyroid cancer and its role in maintaining thyroid CSC self-renewal. We also summarize the recent developments on crosstalk of the Shh pathway with the MAPK and PI3K oncogenic pathways, and its implications for combination therapy.

  19. Sonic Hedgehog Signaling in Thyroid Cancer

    Science.gov (United States)

    Xu, Xiulong; Lu, Yurong; Li, Yi; Prinz, Richard A.

    2017-01-01

    Thyroid cancer is the most common malignancy of the endocrine system. The initiation of thyroid cancer is often triggered by a genetic mutation in the phosphortidylinositol-3 kinase (PI3K) or mitogen-activated protein kinase (MAPK) pathway, such as RAS and BRAF, or by the rearrangement of growth factor receptor tyrosine kinase genes such as RET/PTC. The sonic hedgehog (Shh) pathway is evolutionarily conserved and plays an important role in the embryonic development of normal tissues and organs. Gene mutations in the Shh pathway are involved in basal cell carcinomas (BCC). Activation of the Shh pathway due to overexpression of the genes encoding the components of this pathway stimulates the growth and spread of a wide range of cancer types. The Shh pathway also plays an important role in cancer stem cell (CSC) self-renewal. GDC-0449 and LDE-225, two inhibitors of this pathway, have been approved for treating BCC and are being tested as a single agent or in combination with other drugs for treating various other cancers. Here, we review the recent findings on activation of the Shh pathway in thyroid cancer and its role in maintaining thyroid CSC self-renewal. We also summarize the recent developments on crosstalk of the Shh pathway with the MAPK and PI3K oncogenic pathways, and its implications for combination therapy. PMID:29163356

  20. Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli.

    Science.gov (United States)

    Wang, Zhong Chuan; Gao, Jun; Zi, Shu Ming; Yang, Ming; Du, Peng; Cui, Long

    2013-08-01

    To determine the hedgehog (Hh) signaling pathway correlated with the development of colon cancer and melanosis coli. Protein and mRNA levels of Hh signaling pathway components (sonic hedgehog [Shh], protein patched homolog 1 [Ptch 1], GLI family zinc finger 1 [Gli 1] and suppressor of fused homolog [Drosophila] [Sufu]) in 127 patients with colon cancer, 36 with melanosis coli and 20 adjacent normal mucosal tissues taken from surgical specimens were evaluated using antibody staining and quantitative real-time polymerase chain reaction. In adjacent normal tissue Shh and Ptch1, but not Gli1 or Sufu, were weakly expressed and mainly in the lining epithelium of the colonic mucosa. In cancerous tissues Shh and Gli1 were uniformly strong while Ptch1 was patchy and weak, and Sufu uniformly weak, which paralleled their levels of corresponding mRNA. Elevated protein levels of Shh and Ptch were significantly associated with mucinous colonic tissues. Elevated Sufu protein levels were positively correlated with the diameter and invasion of the tumor. In patients with melanosis coli, mRNA levels of Shh, Ptch1, Gli1 and Sufu were very low, which was similar to those of adjacent normal tissues; but protein levels of Shh, Ptch1 and Gli1, but not Sufu, were high, which was similar to those of cancerous tissues. The mRNA and protein levels of Hh pathway components are aberrantly elevated in colon cancer, which may be the potential molecular classification markers. Further studies are required to determine the role of melanosis coli in the colon tumorigenesis. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  1. Celiac Disease Histopathology Recapitulates Hedgehog Downregulation, Consistent with Wound Healing Processes Activation.

    Directory of Open Access Journals (Sweden)

    Stefania Senger

    Full Text Available In celiac disease (CD, intestinal epithelium damage occurs secondary to an immune insult and is characterized by blunting of the villi and crypt hyperplasia. Similarities between Hedgehog (Hh/BMP4 downregulation, as reported in a mouse model, and CD histopathology, suggest mechanistic involvement of Hh/BMP4/WNT pathways in proliferation and differentiation of immature epithelial cells in the context of human intestinal homeostasis and regeneration after damage. Herein we examined the nature of intestinal crypt hyperplasia and involvement of Hh/BMP4 in CD histopathology.Immunohistochemistry, qPCR and in situ hybridization were used to study a cohort of 24 healthy controls (HC and 24 patients with diagnosed acute celiac disease (A-CD intestinal biopsies. In A-CD we observed an increase in cells positive for Leucin-rich repeat-containing G protein-coupled receptor 5 (LGR5, an epithelial stem cell specific marker and expansion of WNT responding compartment. Further, we observed alteration in number and distribution of mesenchymal cells, predicted to be part of the intestinal stem cells niche. At the molecular level we found downregulation of indian hedgehog (IHH and other components of the Hh pathway, but we did not observe a concurrent downregulation of BMP4. However, we observed upregulation of BMPs antagonists, gremlin 1 and gremlin 2.Our data suggest that acute CD histopathology partially recapitulates the phenotype reported in Hh knockdown models. Specifically, Hh/BMP4 paradigm appears to be decoupled in CD, as the expansion of the immature cell population does not occur consequent to downregulation of BMP4. Instead, we provide evidence that upregulation of BMP antagonists play a key role in intestinal crypt hyperplasia. This study sheds light on the molecular mechanisms underlying CD histopathology and the limitations in the use of mouse models for celiac disease.

  2. Neuronal plasticity in the hedgehog supraoptic nucleus during hibernation.

    Science.gov (United States)

    Sanchez-Toscano, F; Caminero, A A; Machin, C; Abella, G

    1989-01-01

    The purpose of the present study was to identify processes of plasticity in the receptive field of neurosecretory neurons of the supraoptic nucleus during hibernation in the hedgehog, in order to correlate them with the increased neurosecretory activity observed in this nucleus during this annual period. Using the Rapid Golgi method, a quantitative study was conducted in the receptive field of bipolar and multipolar neurons (the main components of the nucleus). Results indicate a generalized increase in the following characteristics: (1) number of dendritic spines per millimeter along the dendritic shafts; (2) degree of branching in the dendritic field; and (3) dendritic density around the neuronal soma. These data demonstrate modification of the dendritic field in the supraoptic nucleus during hibernation, a change undoubtedly related to functional conditions. Since the observed changes affect structures such as dendritic spines which are directly related to the arrival of neural afferences, the discussion is centered on the types of stimuli which may be responsible for the observed processes.

  3. Assessing net carbon sequestration on urban and community forests of northern New England, USA

    Science.gov (United States)

    Daolan Zheng; Mark J. Ducey; Linda S. Heath

    2013-01-01

    Urban and community forests play an important role in the overall carbon budget of the USA. Accurately quantifying carbon sequestration by these forests can provide insight for strategic planning to mitigate greenhouse gas effects on climate change. This study provides a new methodology to estimate net forest carbon sequestration (FCS) in urban and community lands of...

  4. Effects of lanthanum and acid rain stress on the bio-sequestration of lanthanum in phytoliths in germinated rice seeds

    Science.gov (United States)

    Si, Yong; Wang, Lihong; Huang, Xiaohua

    2018-01-01

    REEs in the environment can be absorbed by plants and sequestered by plant phytoliths. Acid rain can directly or indirectly affect plant physiological functions. Currently, the effects of REEs and acid rain on phytolith-REEs complex in plants are not yet fully understood. In this study, a high-silicon accumulation crop, rice (Oryza sativa L.), was selected as a representative of plants, and orthogonal experiments were conducted under various levels of lanthanum [La(III)] and pH. The results showed that various La(III) concentrations could significantly improve the efficiency and sequestration of phytolith La(III) in germinated rice seeds. A pH of 4.5 promoted phytolith La(III) sequestration, while a pH of 3.5 inhibited sequestration. Compared with the single treatment with La(III), the combination of La(III) and acid rain inhibited the efficiency and sequestration of phytolith La(III). Correlation analysis showed that the efficiency of phytolith La(III) sequestration had no correlation with the production of phytolith but was closely correlated with the sequestration of phytolith La(III) and the physiological changes of germinated rice seeds. Phytolith morphology was an important factor affecting phytolith La(III) sequestration in germinated rice seeds, and the effect of tubes on sequestration was more significant than that of dumbbells. This study demonstrated that the formation of the phytolith and La(III) complex could be affected by exogenous La(III) and acid rain in germinated rice seeds. PMID:29763463

  5. Yield and soil carbon sequestration in grazed pastures sown with two or five forage species

    Science.gov (United States)

    Increasing plant species richness is often associated with an increase in productivity and associated ecosystem services such as soil C sequestration. In this paper we report on a nine-year experiment to evaluate the relative forage production and C sequestration potential of grazed pastures sown to...

  6. Carbon sequestration potential for forage and pasture systems

    Science.gov (United States)

    Grassland soils represent a large reservoir of organic and inorganic carbon. Regionally, grasslands are annual CO2 sources or sinks depending on crop and soil management, current soil organic carbon (SOC) concentration and climate. Land management changes (LMC) impact SOC sequestration rate, the du...

  7. Bile acid sequestrants

    DEFF Research Database (Denmark)

    Hansen, Morten; Sonne, David P; Knop, Filip K

    2014-01-01

    Bile acids are synthesized in the liver from cholesterol and have traditionally been recognized for their role in absorption of lipids and in cholesterol homeostasis. In recent years, however, bile acids have emerged as metabolic signaling molecules that are involved in the regulation of lipid...... and glucose metabolism, and possibly energy homeostasis, through activation of the bile acid receptors farnesoid X receptor (FXR) and TGR5. Bile acid sequestrants (BASs) constitute a class of drugs that bind bile acids in the intestine to form a nonabsorbable complex resulting in interruption...... of the enterohepatic circulation. This increases bile acid synthesis and consequently reduces serum low-density lipoprotein cholesterol. Also, BASs improve glycemic control in patients with type 2 diabetes. Despite a growing understanding of the impact of BASs on glucose metabolism, the mechanisms behind their glucose...

  8. [Greenhouse gas emissions, carbon leakage and net carbon sequestration from afforestation and forest management: A review.

    Science.gov (United States)

    Liu, Bo Jie; Lu, Fei; Wang, Xiao Ke; Liu, Wei Wei

    2017-02-01

    Forests play an important role in climate change mitigation and concentration of CO 2 reduction in the atmosphere. Forest management, especially afforestation and forest protection, could increase carbon stock of forests significantly. Carbon sequestration rate of afforestation ranges from 0.04 to 7.52 t C·hm -2 ·a -1 , while that of forest protection is 0.33-5.20 t C·hm -2 ·a -1 . At the same time, greenhouse gas (GHG) is generated within management boundary due to the production and transportation of the materials consumed in relevant activities of afforestation and forest management. In addition, carbon leakage is also generated outside boundary from activity shifting, market effects and change of environments induced by forest management. In this review, we summarized the definition of emission sources of GHG, monitoring methods, quantity and rate of greenhouse gas emissions within boundary of afforestation and forest management. In addition, types, monitoring methods and quantity of carbon leakage outside boundary of forest management were also analyzed. Based on the reviewed results of carbon sequestration, we introduced greenhouse gas emissions within boundary and carbon leakage, net carbon sequestration as well as the countervailing effects of greenhouse gas emissions and carbon leakage to carbon sequestration. Greenhouse gas emissions within management boundary counteract 0.01%-19.3% of carbon sequestration, and such counteraction could increase to as high as 95% considering carbon leakage. Afforestation and forest management have substantial net carbon sequestration benefits, when only taking direct greenhouse gas emissions within boundary and measurable carbon leakage from activity shifting into consideration. Compared with soil carbon sequestration measures in croplands, afforestation and forest management is more advantageous in net carbon sequestration and has better prospects for application in terms of net mitigation potential. Along with the

  9. Carbon sequestration and natural longleaf pine ecosystems

    Science.gov (United States)

    Ralph S. Meldahl; John S. Kush

    2006-01-01

    A fire-maintained longleaf pine (Pinus palustris Mill.) ecosystem may offer the best option for carbon (C) sequestration among the southern pines. Longleaf is the longest living of the southern pines, and products from longleaf pine will sequester C longer than most since they are likely to be solid wood products such as structural lumber and poles....

  10. Temporal Considerations of Carbon Sequestration in LCA

    Science.gov (United States)

    James Salazar; Richard Bergman

    2013-01-01

    Accounting for carbon sequestration in LCA illustrates the limitations of a single global warming characterization factor. Typical cradle-to-grave LCA models all emissions from end-of-life processes and then characterizes these flows by IPCC GWP (100-yr) factors. A novel method estimates climate change impact by characterizing annual emissions with the IPCC GHG forcing...

  11. Forest management and carbon sequestration in the Mediterranean region: A review

    Directory of Open Access Journals (Sweden)

    Ricardo Ruiz-Peinado

    2017-10-01

    Full Text Available Aim of the study: To review and acknowledge the value of carbon sequestration by forest management in the Mediterranean area. Material and methods: We review the main effects of forest management by comparing the effects of silvicultural systems (even-aged vs. uneven-aged stands, coppice systems, agroforestry systems, silvicultural options (thinning, rotation period, species composition, afforestation, harvesting, fire impact or effects of shrub layer on carbon sequestration in the Mediterranean area. Main results: We illustrate as forest management can clearly improve forest carbon sequestration amounts. We conclude that forest management is an effective way to maintain and enhance high carbon sequestration rates in order to cope with climate change and provision of ecosystem services. We also think that although much effort has been put into this topic research, there are still certain gaps that must be dealt with to increase our scientific knowledge and in turn transfer this knowledge to forest practitioners in order to achieve sustainable management aimed at mitigating climate change. Research highlights: It is important to underline the importance of forests in the carbon cycle as this role can be enhanced by forest managers through sustainable forest management. The effects of different management options or disturbances can be critical as regards mitigating climate change. Understanding the effects of forest management is even more important in the Mediterranean area, given that the current high climatic variability together with historical human exploitation and disturbance events make this area more vulnerable to the effects of climate change

  12. Prospects for carbon capture and sequestration technologies assuming their technological learning

    International Nuclear Information System (INIS)

    Riahi, Keywan; Rubin, Edward S.; Schrattenholzer, Leo

    2004-01-01

    This paper analyzes potentials of carbon capture and sequestration technologies (CCS) in a set of long-term energy-economic-environmental scenarios based on alternative assumptions for technological progress of CCS. In order to get a reasonable guide to future technological progress in managing CO 2 emissions, we review past experience in controlling sulfur dioxide emissions (SO 2 ) from power plants. By doing so, we quantify a 'learning curve' for CCS, which describes the relationship between the improvement of costs due to accumulation of experience in CCS construction. We incorporate the learning curve into the energy modeling framework MESSAGE-MACRO and develop greenhouse gas emissions scenarios of economic, demographic, and energy demand development, where alternative policy cases lead to the stabilization of atmospheric CO 2 concentrations at 550 parts per million by volume (ppmv) by the end of the 21st century. Due to the assumed technological learning, costs of the emissions reduction for CCS drop rapidly and in parallel with the massive introduction of CCS on the global scale. Compared to scenarios based on static cost assumptions for CCS, the contribution of carbon sequestration is about 50 percent higher in the case of learning resulting in cumulative sequestration of CO 2 ranging from 150 to 250 billion (10 9 ) tons carbon during the 21st century. The results illustrate that carbon capture and sequestration is one of the obvious priority candidates for long-term technology policies and enhanced R and D efforts to hedge against the risk associated with high environmental impacts of climate change

  13. Osteocalcin expressing cells from tendon sheaths in mice contribute to tendon repair by activating Hedgehog signaling

    OpenAIRE

    Wang, Yi; Zhang, Xu; Huang, Huihui; Xia, Yin; Yao, YiFei; Mak, Arthur Fuk-Tat; Yung, Patrick Shu-Hang; Chan, Kai-Ming; Wang, Li; Zhang, Chenglin; Huang, Yu; Mak, Kingston King-Lun

    2017-01-01

    Both extrinsic and intrinsic tissues contribute to tendon repair, but the origin and molecular functions of extrinsic tissues in tendon repair are not fully understood. Here we show that tendon sheath cells harbor stem/progenitor cell properties and contribute to tendon repair by activating Hedgehog signaling. We found that Osteocalcin (Bglap) can be used as an adult tendon-sheath-specific marker in mice. Lineage tracing experiments show that Bglap-expressing cells in adult sheath tissues pos...

  14. Trace metal mobilization in an experimental carbon sequestration scenario

    Energy Technology Data Exchange (ETDEWEB)

    Marcon, Virginia [University of Wyoming, Geology and Geophysics, Laramie, WY. 82070 (United States); Kaszuba, John [University of Wyoming, Geology and Geophysics, Laramie, WY. 82070 (United States); Univeristy of Wyoming, School of Energy Resources, Larmaie, WY. 82070 (United States)

    2013-07-01

    Mobilizing trace metals with injection of supercritical CO{sub 2} into deep saline aquifers is a concern for geologic carbon sequestration. Hydrothermal experiments investigate the release of harmful metals from two zones of a sequestration injection reservoir: at the cap-rock-reservoir boundary and deeper within the reservoir, away from the cap-rock. In both systems, Cd, Cr, Cu, Pb, and Zn behave in a similar manner, increasing in concentration with injection, but subsequently decreasing in concentration over time. SEM images and geochemical models indicate initial dissolution of minerals and precipitation of Ca-Mg-Fe carbonates, metal sulfides (i.e. Fe, As, Ag, and Co sulfides), and anhydrite in both systems. The results suggest that Ba, Cu, and Zn will not be contaminants of concern, but Pb, Fe, and As may require careful attention. (authors)

  15. The value of carbon sequestration and storage in coastal habitats

    Science.gov (United States)

    Beaumont, N. J.; Jones, L.; Garbutt, A.; Hansom, J. D.; Toberman, M.

    2014-01-01

    Coastal margin habitats are globally significant in terms of their capacity to sequester and store carbon, but their continuing decline, due to environmental change and human land use decisions, is reducing their capacity to provide this ecosystem service. In this paper the UK is used as a case study area to develop methodologies to quantify and value the ecosystem service of blue carbon sequestration and storage in coastal margin habitats. Changes in UK coastal habitat area between 1900 and 2060 are documented, the long term stocks of carbon stored by these habitats are calculated, and the capacity of these habitats to sequester CO2 is detailed. Changes in value of the carbon sequestration service of coastal habitats are then projected for 2000-2060 under two scenarios, the maintenance of the current state of the habitat and the continuation of current trends of habitat loss. If coastal habitats are maintained at their current extent, their sequestration capacity over the period 2000-2060 is valued to be in the region of £1 billion UK sterling (3.5% discount rate). However, if current trends of habitat loss continue, the capacity of the coastal habitats both to sequester and store CO2 will be significantly reduced, with a reduction in value of around £0.25 billion UK sterling (2000-2060; 3.5% discount rate). If loss-trends due to sea level rise or land reclamation worsen, this loss in value will be greater. This case study provides valuable site specific information, but also highlights global issues regarding the quantification and valuation of carbon sequestration and storage. Whilst our ability to value ecosystem services is improving, considerable uncertainty remains. If such ecosystem valuations are to be incorporated with confidence into national and global policy and legislative frameworks, it is necessary to address this uncertainty. Recommendations to achieve this are outlined.

  16. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng

    2014-12-03

    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  17. Instability of the hedgehog shape for the octet baryon in the chiral quark soliton model

    OpenAIRE

    Akiyama, Satoru; Futami, Yasuhiko

    2003-01-01

    In this paper the stability of the hedgehog shape of the chiral soliton is studied for the octet baryon with the SU(3) chiral quark soliton model. The strangeness degrees of freedom are treated by a simplified bound-state approach, which omits the locality of the kaon wave function. The mean field approximation for the flavor rotation is applied to the model. The classical soliton changes shape according to the strangeness. The baryon appears as a rotational band of the combined system of the...

  18. A simulation method for the rapid screening of potential depleted oil reservoirs for CO2 sequestration

    International Nuclear Information System (INIS)

    Bossie-Codreanu, D.; Le Gallo, Y.

    2004-01-01

    The reduction of greenhouse gases emission is a growing concern of many industries. The oil and gas industry has a long commercial practice of gas injection, enhanced oil recovery (EOR) and gas storage. Using a depleted oil or gas reservoir for CO 2 storage has several interesting advantages. The long-term risk analysis of the CO 2 behavior and its impact on the environment is a major concern. That is why the selection of an appropriate reservoir is crucial to the success of a sequestration operation. Our modeling study, based on a synthetic reservoir, quantifies uncertainties due to reservoir parameters in order to establish a set of guidelines to select the most appropriate depleted reservoirs. Several production and sequestration scenarios are investigated in order to quantify key parameter for CO 2 storage. The influence of parameters such as API gravity, heterogeneity (Dykstra-Parson coefficient), pressure support (water injection) and cap rock integrity are analyzed. Estimation of sequestration capacity is proposed through a sequestration factor (SF) estimated for different reservoir production drives. Multiple regression relationships were developed, allowing SF estimation. CO 2 sequestration optimization highlights the best clean oil recovery strategy (CO 2 injection and/or oil production)

  19. Enhanced Coal Bed Methane Recovery and CO2 Sequestration in the Powder River Basin

    Energy Technology Data Exchange (ETDEWEB)

    Eric P. Robertson

    2010-06-01

    Unminable coal beds are potentially large storage reservoirs for the sequestration of anthropogenic CO2 and offer the benefit of enhanced methane production, which can offset some of the costs associated with CO2 sequestration. The objective of this report is to provide a final topical report on enhanced coal bed methane recovery and CO2 sequestration to the U.S. Department of Energy in fulfillment of a Big Sky Carbon Sequestration Partnership milestone. This report summarizes work done at Idaho National Laboratory in support of Phase II of the Big Sky Carbon Sequestration Partnership. Research that elucidates the interaction of CO2 and coal is discussed with work centering on the Powder River Basin of Wyoming and Montana. Sorption-induced strain, also referred to as coal swelling/shrinkage, was investigated. A new method of obtaining sorption-induced strain was developed that greatly decreases the time necessary for data collection and increases the reliability of the strain data. As coal permeability is a strong function of sorption-induced strain, common permeability models were used to fit measured permeability data, but were found inadequate. A new permeability model was developed that can be directly applied to coal permeability data obtained under laboratory stress conditions, which are different than field stress conditions. The coal permeability model can be used to obtain critical coal parameters that can be applied in field models. An economic feasibility study of CO2 sequestration in unminable coal seams in the Powder River Basin of Wyoming was done. Economic analyses of CO2 injection options are compared. Results show that injecting flue gas to recover methane from CBM fields is marginally economical; however, this method will not significantly contribute to the need to sequester large quantities of CO2. Separating CO2 from flue gas and injecting it into the unminable coal zones of the Powder River Basin seam is currently uneconomical, but can

  20. Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition

    Directory of Open Access Journals (Sweden)

    Takashi Onikubo

    2015-03-01

    Full Text Available Nucleoplasmin (Npm is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg.

  1. Sequestration of arsenic in ombrotrophic peatlands

    Science.gov (United States)

    Rothwell, James; Hudson-Edwards, Karen; Taylor, Kevin; Polya, David; Evans, Martin; Allott, Tim

    2014-05-01

    Peatlands can be important stores of arsenic but we are lacking spectroscopic evidence of the sequestration pathways of this toxic metalloid in peatland environments. This study reports on the solid-phase speciation of anthropogenically-derived arsenic in atmospherically contaminated peat from the Peak District National Park (UK). Surface and sub-surface peat samples were analysed by synchrotron X-ray absorption spectroscopy on B18 beamline at Diamond Light Source (UK). The results suggest that there are contrasting arsenic sequestration mechanisms in the peat. The bulk arsenic speciation results, in combination with strong arsenic-iron correlations at the surface, suggest that iron (hydr)oxides are key phases for the immobilisation of arsenic at the peat surface. In contrast, the deeper peat samples are dominated by arsenic sulphides (arsenopyrite, realgar and orpiment). Given that these peats receive inputs solely from the atmosphere, the presence of these sulphide phases suggests an in-situ authigenic formation. Redox oscillations in the peat due to a fluctuating water table and an abundant store of legacy sulphur from historic acid rain inputs may favour the precipitation of arsenic sequestering sulphides in sub-surface horizons. Oxidation-induced loss of these arsenic sequestering sulphur species by water table drawdown has important implications for the mobility of arsenic and the quality of waters draining peatlands.

  2. Neocortical layers I and II of the hedgehog (Erinaceus europaeus). I. Intrinsic organization.

    Science.gov (United States)

    Valverde, F; Facal-Valverde, M V

    1986-01-01

    The intrinsic organization and interlaminar connections in neocortical layers I and II have been studied in adult hedgehogs (Erinaceus europaeus) using the Golgi method. Layer I contains a dense plexus of horizontal fibers, the terminal dendritic bouquets of pyramidal cells of layer II and of underlying layers, and varieties of intrinsic neurons. Four main types of cells were found in layer I. Small horizontal cells represent most probably persisting foetal horizontal cells described for other mammals. Large horizontal cells, tufted cells, and spinous horizontal cells were also found in this layer. Layer II contains primitive pyramidal cells representing the most outstanding feature of the neocortex of the hedgehog. Most pyramidal cells in layer II have two, three or more apical dendrites, richly covered by spines predominating over the basal dendrites. These cells resemble pyramidal cells found in the piriform cortex, hippocampus and other olfactory areas. It is suggested that the presence of these neurons reflects the retention of a primitive character in neocortical evolution. Cells with intrinsic axons were found among pyramidal cells in layer II. These have smooth dendrites penetrating layer I and local axons forming extremely complex terminal arborizations around the bodies and proximal dendritic portions of pyramidal cells. They most probably effect numerous axo-somatic contacts resembling basket cells. The similarity of some axonal terminals with the chandelier type of axonal arborization is discussed. Other varieties of cells located in deep cortical layers and having ascending axons for layers I and II were also studied. It is concluded that the two first neocortical layers represent a level of important integration in this primitive mammal.

  3. Capture and geological sequestration of CO2: fighting against global warming

    International Nuclear Information System (INIS)

    Czernichowski-Lauriol, I.

    2006-01-01

    In order to take up the global warming challenge, a set of emergency measures is to be implemented: energy saving, clean transportation systems, development of renewable energy sources.. CO 2 sequestration of massive industrial emission sources inside deep geologic formations is another promising solution, which can contribute to the division by two of the world CO 2 emissions between today and 2050. The CO 2 capture and sequestration industry is developing. Research projects and pilot facilities are on the increase over the world. Their aim is to warrant the efficiency and security of this technology over the centuries to come. (J.S.)

  4. Correlation between hedgehog (hh) protein family and brain-derived neurotrophic factor (bdnf) in autism spectrum disorder (asd)

    International Nuclear Information System (INIS)

    Halepoto, D.M.; Bashir, S.

    2015-01-01

    To determine the correlation of Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Brain-Derived Neurotrophic Factor (BDNF) in children with Autism Spectrum Disorder (ASD). Study Design: An observational, comparative study. Place and Duration of Study: Autism Research and Treatment Center, Al-Amodi Autism Research Chair, Department of Physiology, Faculty of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from October 2011 to May 2012. Methodology: Serum levels of SHH, IHH and BDNF were determined in recently diagnosed autistic patients and age matched healthy children (n=25), using the Enzyme-Linked Immunosorbent Assay (ELISA). Childhood Autism Rating Scale (CARS) was used for the assessment of autistic severity. Spearman correlation co-efficient-r was determined. Results: The serum levels of IHH and SHH were significantly higher in autistic subjects than those of control subjects. There was significant correlation between age and IHH (r = 0.176, p = 0.03), BDNF and severe IHH (r = 0.1763, p = 0.003), and severe BDNF and severe SHH (r = 0.143, p < 0.001). However, there were no significant relationships among the serum levels of SHH, IHH and BDNF and the CARS score, age or gender. Conclusion: The findings support a correlation between SHH, IHH and BDNF in autistic children, suggesting their pathological role in autism. (author)

  5. The NatCarb geoportal: Linking distributed data from the Carbon Sequestration Regional Partnerships

    Science.gov (United States)

    Carr, T.R.; Rich, P.M.; Bartley, J.D.

    2007-01-01

    The Department of Energy (DOE) Carbon Sequestration Regional Partnerships are generating the data for a "carbon atlas" of key geospatial data (carbon sources, potential sinks, etc.) required for rapid implementation of carbon sequestration on a broad scale. The NATional CARBon Sequestration Database and Geographic Information System (NatCarb) provides Web-based, nation-wide data access. Distributed computing solutions link partnerships and other publicly accessible repositories of geological, geophysical, natural resource, infrastructure, and environmental data. Data are maintained and enhanced locally, but assembled and accessed through a single geoportal. NatCarb, as a first attempt at a national carbon cyberinfrastructure (NCCI), assembles the data required to address technical and policy challenges of carbon capture and storage. We present a path forward to design and implement a comprehensive and successful NCCI. ?? 2007 The Haworth Press, Inc. All rights reserved.

  6. Occurrence and sequestration of toxins in food chains.

    Science.gov (United States)

    Mebs, D

    1998-11-01

    Animals may acquire toxicity by absorbing toxic compounds from their food, e.g. from plants or other animals. Sequestration and accumulation of toxins may provide protection from predators, which learn to avoid this prey because of unpleasant experiences such as bitter taste. This is a common phenomenon in marine as well as in terrestrial ecosystems. Moreover, toxins may enter food chains where they accumulate reaching high, often lethal concentrations. Palytoxin which had been primarily detected in marine zoanthids (Palythoa sp.), occurs also in a wide range of other animals, e.g. in sponges, corals, shellfish, polychaetes and crustaceans, but also in fish, which feed on crustaceans and zoanthids as well. These animals exhibit a high resistance to the toxin's action. The mechanisms which protect the Na+, K+-ATPase of their cell membranes, the primary target of palytoxin, is unknown. Sequestration of the toxin by other animals may cause health problems due to food poisoning.

  7. Phylogenetic variation of phytolith carbon sequestration in bamboos.

    Science.gov (United States)

    Li, Beilei; Song, Zhaoliang; Li, Zimin; Wang, Hailong; Gui, Renyi; Song, Ruisheng

    2014-04-16

    Phytoliths, the amorphous silica deposited in plant tissues, can occlude organic carbon (phytolith-occluded carbon, PhytOC) during their formation and play a significant role in the global carbon balance. This study explored phylogenetic variation of phytolith carbon sequestration in bamboos. The phytolith content in bamboo varied substantially from 4.28% to 16.42%, with the highest content in Sasa and the lowest in Chimonobambusa, Indocalamus and Acidosasa. The mean PhytOC production flux and rate in China's bamboo forests were 62.83 kg CO2 ha(-1) y(-1) and 4.5 × 10(8)kg CO2 y(-1), respectively. This implies that 1.4 × 10(9) kg CO2 would be sequestered in world's bamboo phytoliths because the global bamboo distribution area is about three to four times higher than China's bamboo. Therefore, both increasing the bamboo area and selecting high phytolith-content bamboo species would increase the sequestration of atmospheric CO2 within bamboo phytoliths.

  8. Relevance of hair and spines of the European hedgehog (Erinaceus europaeus) as biomonitoring tissues for arsenic and metals in relation to blood

    NARCIS (Netherlands)

    Vermeulen, F.; Havé, D' H.; Mubiana, V.K.; Brink, van den N.W.; Blust, R.; Bervoets, L.; Coen, De W.

    2009-01-01

    Hair has been proven to be suitable for non-destructive and non-invasive exposure assessments in human and mammal populations. A previous study with European hedgehog (Erinaceus europaeus) showed that, for some metals, hair and spine metal concentrations were positively correlated to levels in

  9. Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.

    Science.gov (United States)

    Chapouly, Candice; Yao, Qinyu; Vandierdonck, Soizic; Larrieu-Lahargue, Frederic; Mariani, John N; Gadeau, Alain-Pierre; Renault, Marie-Ange

    2016-02-01

    Microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. In the present paper, we have identified the role of Hedgehog (Hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired Hh signalling in endothelial cells (ECs) on nerve function. By using Desert Hedgehog (Dhh)-deficient mice, we have revealed, that in the absence of Dhh, endoneurial capillaries are abnormally dense and permeable. Furthermore, Smoothened (Smo) conditional KO mice clarified that this increased vessel permeability is specifically due to impaired Hh signalling in ECs and is associated with a down-regulation of Claudin5 (Cldn5). Moreover, impairment of Hh signalling in ECs was sufficient to induce hypoalgesia and neuropathic pain. Finally in Lepr(db/db) type 2 diabetic mice, the loss of Dhh expression observed in the nerve was shown to be associated with increased endoneurial capillary permeability and decreased Cldn5 expression. Conversely, systemic administration of the Smo agonist SAG increased Cldn5 expression, decreased endoneurial capillary permeability, and restored thermal algesia to diabetic mice, demonstrating that loss of Dhh expression is crucial in the development of diabetic neuropathy. The present work demonstrates the critical role of Dhh in maintaining blood nerve barrier integrity and demonstrates for the first time that endothelial dysfunction is sufficient to induce neuropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  10. Crystallization of protein–ligand complexes

    International Nuclear Information System (INIS)

    Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

    2007-01-01

    Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

  11. Non-destructive pollution exposure assessment in the European hedgehog (Erinaceus europaeus): IV hair versus soil analysis in exposure and risk assessment of organochlorine compounds

    NARCIS (Netherlands)

    Havé, D' H.; Scheirs, J.; Covaci, A.; Brink, van den N.W.; Verhagen, R.; Coen, De W.

    2007-01-01

    Few ecotoxicological studies on mammals use non-destructive methodologies, despite the growing ethical concern over the use of destructive sampling methods. In the present study we assessed exposure of hedgehogs (Erinaceus europaeus) to polychlorinated biphenyls (PCBs),

  12. Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3-E1 cells

    Science.gov (United States)

    Deng, Ang; Zhang, Hongqi; Hu, Minyu; Liu, Shaohua; Gao, Qile; Wang, Yuxiang; Guo, Chaofeng

    2017-01-01

    Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation. In the present study, Ihh was knocked down in osteoblast MC3T3-E1 cells using short hairpin RNA, to investigate the function of Ihh in osteoblast proliferation and differentiation and to examine the potential mechanism through which Ihh induces osteoblast apoptosis and cell cycle arrest. It was observed that the knockdown of Ihh induced a marked inhibition of cell growth and increased the apoptosis rate compared with the negative control osteoblasts. Downregulation of Ihh resulted in a cell cycle arrest at the G1 to S phase boundary in osteoblasts. In addition, the knockdown of Ihh decreased the alkaline phosphatase activity and mineral deposition of osteoblasts. The inhibitory roles of Ihh downregulation in osteoblast growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic homolog and tumor necrosis factor receptor superfamily member 11B/tumor necrosis factor ligand superfamily member 11 signaling pathways. Manipulating either Ihh expression or its signaling components may be of benefit for the treatment of skeletal diseases. PMID:28990069

  13. Integrating science, economics and law into policy: The case of carbon sequestration in climate change policy

    Science.gov (United States)

    Richards, Kenneth

    Carbon sequestration, the extraction and storage of carbon from the atmosphere by biomass, could potentially provide a cost-effective means to reduce net greenhouse gas emissions. The claims on behalf of carbon sequestration may be inadvertently overstated, however. Several key observations emerge from this study. First, although carbon sequestration studies all report results in terms of dollars per ton, the definition of that term varies significantly, meaning that the results of various analyses can not be meaningfully compared. Second, when carbon sequestration is included in an energy-economy model of climate change policy, it appears that carbon sequestration could play a major, if not dominant role in a national carbon emission abatement program, reducing costs of emissions stabilization by as much as 80 percent, saving tens of billions of dollars per year. However, the results are very dependant upon landowners' perceived risk. Studies may also have overstated the potential for carbon sequestration because they have not considered the implementation process. This study demonstrates that three factors will reduce the cost-effectiveness of carbon sequestration. First, the implementation costs associated with measurement and governance of the government-private sector relation are higher than in the case of carbon source control. Second, legal constraints limit the range of instruments that the government can use to induce private landowners to expand their carbon sinks. The government will likely have to pay private parties to expand their sinks, or undertake direct government production. In either case, additional revenues will be required, introducing social costs associated with excess burden. Third, because of the very long time involved in developing carbon sinks (up to several decades) the government may not be able to make credible commitments against exactions of one type or another that would effectively reduce the value of private sector investments

  14. Carbon dioxide sequestration by mineral carbonation. Feasibility of enhanced natural weathering as a CO2 emission reduction technology

    International Nuclear Information System (INIS)

    Huijgen, W.J.J.

    2007-01-01

    A possible technology that can contribute to the reduction of carbon dioxide emissions is CO2 sequestration by mineral carbonation. The basic concept behind mineral CO2 sequestration is the mimicking of natural weathering processes in which calcium or magnesium containing minerals react with gaseous CO2 and form solid calcium or magnesium carbonates. Potential advantages of mineral CO2 sequestration compared to, e.g., geological CO2 storage include (1) the permanent and inherently safe sequestration of CO2, due to the thermodynamic stability of the carbonate product formed and (2) the vast potential sequestration capacity, because of the widespread and abundant occurrence of suitable feedstock. In addition, carbonation is an exothermic process, which potentially limits the overall energy consumption and costs of CO2 emission reduction. However, weathering processes are slow, with timescales at natural conditions of thousands to millions of years. For industrial implementation, a reduction of the reaction time to the order of minutes has to be achieved by developing alternative process routes. The aim of this thesis is an investigation of the technical, energetic, and economic feasibility of CO2 sequestration by mineral carbonation. In Chapter 1 the literature published on CO2 sequestration by mineral carbonation is reviewed. Among the potentially suitable mineral feedstock for mineral CO2 sequestration, Ca-silicates, more particularly wollastonite (CaSiO3), a mineral ore, and steel slag, an industrial alkaline solid residue, are selected for further research. Alkaline Ca-rich residues seem particularly promising, since these materials are inexpensive and available near large industrial point sources of CO2. In addition, residues tend to react relatively rapidly with CO2 due to their (geo)chemical instability. Various process routes have been proposed for mineral carbonation, which often include a pre-treatment of the solid feedstock (e.g., size reduction and

  15. Laboratory investigations into the reactive transport module of carbon dioxide sequestration and geochemical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Heidaryan, E. [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Masjidosolayman Branch; Enayati, M.; Mokhtari, B. [Iranian Offshore Oil Co., Tehran (Iran, Islamic Republic of)

    2008-07-01

    Over long time periods, geological sequestration in some systems shows mineralization effects or mineral sequestration of carbon dioxide, converting the carbon dioxide to a less mobile form. However, a detailed investigation of these geological systems is needed before disposing of carbon dioxide into these formations. Depleted oil and gas reservoirs and underground aquifers are proposed candidates for carbon dioxide injection. This paper presented an experimental investigation into the reactive transport module for handling aquifer sequestration of carbon dioxide and modeling of simultaneous geochemical reactions. Two cases of laboratory carbon dioxide sequestration experiments, conducted for different rock systems were modeled using the fully coupled geochemical compositional simulator. The relevant permeability relationships were compared to determine the best fit with the experimental results. The paper discussed the theory of modeling; geochemical reactions and mineral trapping of carbon dioxide; and application simulator for modeling including the remodeling of flow experiments. It was concluded that simulated changes in porosity and permeability could mimic experimental results to some extent. The study satisfactorily simulated the results of experimental observations and permeability results could be improved if the Kozeny-Carman equation was replaced by the Civan power law. 6 refs., 2 tabs., 21 figs.

  16. Potential for carbon sequestration and mitigation of climate change by irrigation of grasslands

    International Nuclear Information System (INIS)

    Olsson, Alexander; Campana, Pietro Elia; Lind, Mårten; Yan, Jinyue

    2014-01-01

    Highlights: • A generic method for climate change mitigation feasibility of PVWPS is developed. • Restoration of degraded lands in China has large climate change mitigation potential. • PV produces excess electricity included in the mitigation potential of the system. • The benefit is higher than if the PV were to produce electricity for the grid only. - Abstract: The climate change mitigation potential of irrigation powered by a photovoltaic water pumping system (PVWPS) to restore degraded grasslands has been investigated using the Intergovernmental Panel on Climate Change (IPCC) 2006 Guidelines for National Greenhouse Gas Inventories for Agriculture, Forestry and Other Land Use. The purpose of this study is to develop a generic and simple method to estimate the climate change mitigation benefit of a PVWPS. The possibility to develop carbon credits for the carbon offset markets has also been studied comparing carbon sequestration in grasslands to other carbon sequestration projects. The soil carbon sequestration following irrigation of the grassland is calculated as an annual increase in the soil organic carbon pool. The PVWPS can also generate an excess of electricity when irrigation is not needed and the emissions reductions due to substitution of grid electricity give additional climate change mitigation potential. The results from this study show that the carbon sequestration and emissions reductions benefits per land area using a PVWPS for irrigating grasslands are comparable to other carbon sequestration options such as switching to no-till practice. Soil carbon in irrigated grasslands is increased with over 60% relative to severely degraded grasslands and if nitrogen fixing species are introduced the increase in soil organic carbon can be almost 80%. Renewable electricity generation by the PVWPS will further increase the mitigation benefit of the system with 70–90%. When applying the methodology developed in this paper to a case in Qinghai, China

  17. Carbon Sequestration Estimation of Street Trees Based on Point Cloud from Vehicle-Borne Laser Scanning System

    Science.gov (United States)

    Zhao, Y.; Hu, Q.

    2017-09-01

    Continuous development of urban road traffic system requests higher standards of road ecological environment. Ecological benefits of street trees are getting more attention. Carbon sequestration of street trees refers to the carbon stocks of street trees, which can be a measurement for ecological benefits of street trees. Estimating carbon sequestration in a traditional way is costly and inefficient. In order to solve above problems, a carbon sequestration estimation approach for street trees based on 3D point cloud from vehicle-borne laser scanning system is proposed in this paper. The method can measure the geometric parameters of a street tree, including tree height, crown width, diameter at breast height (DBH), by processing and analyzing point cloud data of an individual tree. Four Chinese scholartree trees and four camphor trees are selected for experiment. The root mean square error (RMSE) of tree height is 0.11m for Chinese scholartree and 0.02m for camphor. Crown widths in X direction and Y direction, as well as the average crown width are calculated. And the RMSE of average crown width is 0.22m for Chinese scholartree and 0.10m for camphor. The last calculated parameter is DBH, the RMSE of DBH is 0.5cm for both Chinese scholartree and camphor. Combining the measured geometric parameters and an appropriate carbon sequestration calculation model, the individual tree's carbon sequestration will be estimated. The proposed method can help enlarge application range of vehicle-borne laser point cloud data, improve the efficiency of estimating carbon sequestration, construct urban ecological environment and manage landscape.

  18. Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

    Science.gov (United States)

    Marsh, Lorraine

    2015-01-01

    Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

  19. Quantification of the sequestration of indium 111 labelled platelets

    International Nuclear Information System (INIS)

    Najean, Y.; Picard, N.; Dufour, V.; Rain, J.D.

    1988-01-01

    A simple method is proposed for an accurate quantification of the splenic and/or hepatic sequestration of the 111 In-labelled platelets. It could be allow a better prediction of the efficiency of splenectomy in idiopathic thrombocytopenic purpura [fr

  20. Sequestration of human cytomegalovirus by human renal and mammary epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Twite, Nicolas [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Andrei, Graciela [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Kummert, Caroline [ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium); Donner, Catherine [Department of Obstetrics and Gynecology, Erasme Hospital, Route de Lennik 808, 1070 Brussels (Belgium); Perez-Morga, David [Laboratory of Molecular Parasitology, Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, Gosselies (Belgium); De Vos, Rita [Pathology Department, U.Z. Leuven, Minderbroedersstraat 12, Leuven (Belgium); Snoeck, Robert, E-mail: Robert.Snoeck@Rega.kuleuven.be [Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven (Belgium); Marchant, Arnaud, E-mail: arnaud.marchant@ulb.ac.be [Institute for Medical Immunology, Université Libre de Bruxelles, Rue A. Bolland 8, B-6041 Charleroi (Belgium); ImmuneHealth, Rue A. Bolland 8, B-6041 Charleroi (Belgium)

    2014-07-15

    Urine and breast milk represent the main routes of human cytomegalovirus (HCMV) transmission but the contribution of renal and mammary epithelial cells to viral excretion remains unclear. We observed that kidney and mammary epithelial cells were permissive to HCMV infection and expressed immediate early, early and late antigens within 72 h of infection. During the first 24 h after infection, high titers of infectious virus were measured associated to the cells and in culture supernatants, independently of de novo synthesis of virus progeny. This phenomenon was not observed in HCMV-infected fibroblasts and suggested the sequestration and the release of HCMV by epithelial cells. This hypothesis was supported by confocal and electron microscopy analyses. The sequestration and progressive release of HCMV by kidney and mammary epithelial cells may play an important role in the excretion of the virus in urine and breast milk and may thereby contribute to HCMV transmission. - Highlights: • Primary renal and mammary epithelial cells are permissive to HCMV infection. • HCMV is sequestered by epithelial cells and this phenomenon does not require viral replication. • HCMV sequestration by epithelial cells is reduced by antibodies and IFN-γ.

  1. Soil carbon sequestration potential of permanent pasture and continuous cropping soils in New Zealand.

    Science.gov (United States)

    McNally, Sam R; Beare, Mike H; Curtin, Denis; Meenken, Esther D; Kelliher, Francis M; Calvelo Pereira, Roberto; Shen, Qinhua; Baldock, Jeff

    2017-11-01

    Understanding soil organic carbon (SOC) sequestration is important to develop strategies to increase the SOC stock and, thereby, offset some of the increases in atmospheric carbon dioxide. Although the capacity of soils to store SOC in a stable form is commonly attributed to the fine (clay + fine silt) fraction, the properties of the fine fraction that determine the SOC stabilization capacity are poorly known. The aim of this study was to develop an improved model to estimate the SOC stabilization capacity of Allophanic (Andisols) and non-Allophanic topsoils (0-15 cm) and, as a case study, to apply the model to predict the sequestration potential of pastoral soils across New Zealand. A quantile (90th) regression model, based on the specific surface area and extractable aluminium (pyrophosphate) content of soils, provided the best prediction of the upper limit of fine fraction carbon (FFC) (i.e. the stabilization capacity), but with different coefficients for Allophanic and non-Allophanic soils. The carbon (C) saturation deficit was estimated as the difference between the stabilization capacity of individual soils and their current C concentration. For long-term pastures, the mean saturation deficit of Allophanic soils (20.3 mg C g -1 ) was greater than that of non-Allophanic soils (16.3 mg C g -1 ). The saturation deficit of cropped soils was 1.14-1.89 times that of pasture soils. The sequestration potential of pasture soils ranged from 10 t C ha -1 (Ultic soils) to 42 t C ha -1 (Melanic soils). Although meeting the estimated national soil C sequestration potential (124 Mt C) is unrealistic, improved management practices targeted to those soils with the greatest sequestration potential could contribute significantly to off-setting New Zealand's greenhouse gas emissions. As the first national-scale estimate of SOC sequestration potential that encompasses both Allophanic and non-Allophanic soils, this serves as an informative case study for the international

  2. Carbon storage and sequestration by trees in urban and community areas of the United States.

    Science.gov (United States)

    Nowak, David J; Greenfield, Eric J; Hoehn, Robert E; Lapoint, Elizabeth

    2013-07-01

    Carbon storage and sequestration by urban trees in the United States was quantified to assess the magnitude and role of urban forests in relation to climate change. Urban tree field data from 28 cities and 6 states were used to determine the average carbon density per unit of tree cover. These data were applied to statewide urban tree cover measurements to determine total urban forest carbon storage and annual sequestration by state and nationally. Urban whole tree carbon storage densities average 7.69 kg C m(-2) of tree cover and sequestration densities average 0.28 kg C m(-2) of tree cover per year. Total tree carbon storage in U.S. urban areas (c. 2005) is estimated at 643 million tonnes ($50.5 billion value; 95% CI = 597 million and 690 million tonnes) and annual sequestration is estimated at 25.6 million tonnes ($2.0 billion value; 95% CI = 23.7 million to 27.4 million tonnes). Published by Elsevier Ltd.

  3. Interdisciplinary Investigation of CO2 Sequestration in Depleted Shale Gas Formations

    Energy Technology Data Exchange (ETDEWEB)

    Zoback, Mark D. [Stanford Univ., CA (United States); Kovscek, Anthony R. [Stanford Univ., CA (United States); Wilcox, Jennifer [Stanford Univ., CA (United States)

    2013-09-30

    This project investigates the feasibility of geologic sequestration of CO2 in depleted shale gas reservoirs from an interdisciplinary viewpoint. It is anticipated that over the next two decades, tens of thousands of wells will be drilled in the 23 states in which organic-rich shale gas deposits are found. This research investigates the feasibility of using these formations for sequestration. If feasible, the number of sites where CO2 can be sequestered increases dramatically. The research embraces a broad array of length scales ranging from the ~10 nanometer scale of the pores in the shale formations to reservoir scale through a series of integrated laboratory and theoretical studies.

  4. Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

    OpenAIRE

    Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha; Vaidya, Vidita A.

    2011-01-01

    Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and...

  5. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng; Huang, Jianhua Z; Gao, Xin

    2014-01-01

    Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

  6. The Effect of Gasification Biochar on Soil Carbon Sequestration, Soil Quality and Crop Growth

    DEFF Research Database (Denmark)

    Hansen, Veronika

    and pot and field experiments was used to study the effect of straw and wood biochar on carbon sequestration, soil quality and crop growth. Overall, the biochar amendment improved soil chemical and physical properties and plant growth and showed a potential for soil carbon sequestration without having any......New synergies between agriculture and the energy sector making use of agricultural residues for bioenergy production and recycling recalcitrant residuals to soil may offer climate change mitigation potential through the substitution of fossil fuels and soil carbon sequestration. However, concerns...... have been raised about the potential negative impacts of incorporating bioenergy residuals (biochar) in soil and increasing the removal of crop residues such as straw, possibly reducing important soil functions and services for maintaining soil quality. Therefore, a combination of incubation studies...

  7. Influence of land urbanization on carbon sequestration of urban vegetation: A temporal cooperativity analysis in Guangzhou as an example.

    Science.gov (United States)

    Xu, Qian; Dong, Yu-Xiang; Yang, Ren

    2018-04-13

    Land urbanization can affect carbon sequestration. In this study, the relationships between land urbanization and carbon sequestration of urban vegetation were studied for Guangzhou, China. The methodology was based on land use data from Thematic Mapper (TM) imagery, MODIS13Q1 data, and climate data, and the improved Carnegie-Ames-Stanford approach (CASA) model and linear system models were employed. Characteristics such as the amount of expansion, spatial agglomeration, spatial expansion intensity, and spatial growth of built-up land were analyzed, and the influence of land urbanization (built-up land expansion) on carbon sequestration of urban vegetation was elucidated by a temporal sequential cooperativity analysis. The main results were as follows. (1) Land urbanization had a clear influence on carbon sequestration of urban vegetation in Guangzhou, and the proportion and spatial agglomeration of built-up land showed significant negative correlations with this carbon sequestration; the correlation coefficients were -0.443 and -0.537, respectively, in 2014. (2) The spatial expansion intensity and spatial growth of built-up land showed small correlations with carbon sequestration, and the correlations from 2000 to 2005 were relatively larger than those at other times; this was because the built-up land expansion speed was the fastest during this period. (3) The temporal sequential cooperativity analysis revealed that carbon was lost as natural surfaces were transformed to artificial surfaces, and land urbanization effects on carbon sequestration showed no significant temporal lag. Carbon sequestration of urban vegetation in the city could be improved by adding urban green spaces; however, this would likely take some time as the system recovers. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Interactions between carbon sequestration and shade tree diversity in a smallholder coffee cooperative in El Salvador.

    Science.gov (United States)

    Richards, Meryl Breton; Méndez, V Ernesto

    2014-04-01

    Agroforestry systems have substantial potential to conserve native biodiversity and provide ecosystem services. In particular, agroforestry systems have the potential to conserve native tree diversity and sequester carbon for climate change mitigation. However, little research has been conducted on the temporal stability of species diversity and aboveground carbon stocks in these systems or the relation between species diversity and aboveground carbon sequestration. We measured changes in shade-tree diversity and shade-tree carbon stocks in 14 plots of a 35-ha coffee cooperative over 9 years and analyzed relations between species diversity and carbon sequestration. Carbon sequestration was positively correlated with initial species richness of shade trees. Species diversity of shade trees did not change significantly over the study period, but carbon stocks increased due to tree growth. Our results show a potential for carbon sequestration and long-term biodiversity conservation in smallholder coffee agroforestry systems and illustrate the opportunity for synergies between biodiversity conservation and climate change mitigation. © 2013 Society for Conservation Biology.

  9. Thermodynamic Data for Geochemical Modeling of Carbonate Reactions Associated with CO2 Sequestration - Literature Review

    International Nuclear Information System (INIS)

    Krupka, Kenneth M.; Cantrell, Kirk J.; McGrail, B. Peter

    2010-01-01

    Permanent storage of anthropogenic CO 2 in deep geologic formations is being considered as a means to reduce the concentration of atmospheric CO 2 and thus its contribution to global climate change. To ensure safe and effective geologic sequestration, numerous studies have been completed of the extent to which the CO 2 migrates within geologic formations and what physical and geochemical changes occur in these formations when CO 2 is injected. Sophisticated, computerized reservoir simulations are used as part of field site and laboratory CO 2 sequestration studies. These simulations use coupled multiphase flow-reactive chemical transport models and/or standalone (i.e., no coupled fluid transport) geochemical models to calculate gas solubility, aqueous complexation, reduction/oxidation (redox), and/or mineral solubility reactions related to CO 2 injection and sequestration. Thermodynamic data are critical inputs to modeling geochemical processes. The adequacy of thermodynamic data for carbonate compounds has been identified as an important data requirement for the successful application of these geochemical reaction models to CO 2 sequestration. A review of thermodynamic data for CO 2 gas and carbonate aqueous species and minerals present in published data compilations and databases used in geochemical reaction models was therefore completed. Published studies that describe mineralogical analyses from CO 2 sequestration field and natural analogue sites and laboratory studies were also reviewed to identify specific carbonate minerals that are important to CO 2 sequestration reactions and therefore require thermodynamic data. The results of the literature review indicated that an extensive thermodynamic database exists for CO 2 and CH 4 gases, carbonate aqueous species, and carbonate minerals. Values of Δ f G 298 o and/or log K r,298 o are available for essentially all of these compounds. However, log K r,T o or heat capacity values at temperatures above 298 K exist

  10. Surface evolution and carbon sequestration in disturbed and undisturbed wetland soils of the Hunter estuary, southeast Australia

    Science.gov (United States)

    Howe, A. J.; Rodríguez, J. F.; Saco, P. M.

    2009-08-01

    The aim of this work was to quantify the soil carbon storage and sequestration rates of undisturbed natural wetlands and disturbed wetlands subject to restriction of tidal flow and subsequent rehabilitation in an Australian estuary. Disturbed and undisturbed estuarine wetlands of the Hunter estuary, New South Wales, Australia were selected as the study sites for this research. Vertical accretion rates of estuarine substrates were combined with soil carbon concentrations and bulk densities to determine the carbon store and carbon sequestration rates of the substrates tested. Relationships between estuary water level, soil evolution and vertical accretion were also examined. The carbon sequestration rate of undisturbed wetlands was lower (15% for mangrove and 55% for saltmarsh) than disturbed wetlands, but the carbon store was higher (65% for mangrove and 60% for saltmarsh). The increased carbon sequestration rate of the disturbed wetlands was driven by substantially higher rates of vertical accretion (95% for mangrove and 345% for saltmarsh). Estuarine wetland carbon stores were estimated at 700-1000 Gg C for the Hunter estuary and 3900-5600 Gg C for New South Wales. Vertical accretion and carbon sequestration rates of estuarine wetlands in the Hunter are at the lower end of the range reported in the literature. The comparatively high carbon sequestration rates reported for the disturbed wetlands in this study indicate that wetland rehabilitation has positive benefits for regulation of atmospheric carbon concentrations, in addition to more broadly accepted ecosystem services.

  11. A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

    OpenAIRE

    Tukachinsky, Hanna; Lopez, Lyle V.; Salic, Adrian

    2010-01-01

    In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in wh...

  12. On leakage and seepage from geological carbon sequestration sites

    Energy Technology Data Exchange (ETDEWEB)

    Oldenburg, C.M.; Unger, A.J.A.; Hepple, R.P.; Jordan, P.D.

    2002-07-18

    Geologic carbon sequestration is one strategy for reducing the rate of increase of global atmospheric carbon dioxide (CO{sub 2} ) concentrations (IEA, 1997; Reichle, 2000). As used here, the term geologic carbon sequestration refers to the direct injection of supercritical CO{sub 2} deep into subsurface target formations. These target formations will typically be either depleted oil and gas reservoirs, or brine-filled permeable formations referred to here as brine formations. Injected CO{sub 2} will tend to be trapped by one or more of the following mechanisms: (1) permeability trapping, for example when buoyant supercritical CO{sub 2} rises until trapped by a confining caprock; (2) solubility trapping, for example when CO{sub 2} dissolves into the aqueous phase in water-saturated formations, or (3) mineralogic trapping, such as occurs when CO{sub 2} reacts to produce stable carbonate minerals. When CO{sub 2} is trapped in the subsurface by any of these mechanisms, it is effectively sequestered away from the atmosphere where it would otherwise act as a greenhouse gas. The purpose of this report is to summarize our work aimed at quantifying potential CO{sub 2} seepage due to leakage from geologic carbon sequestration sites. The approach we take is to present first the relevant properties of CO{sub 2} over the range of conditions from the deep subsurface to the vadose zone (Section 2), and then discuss conceptual models for how leakage might occur (Section 3). The discussion includes consideration of gas reservoir and natural gas storage analogs, along with some simple estimates of seepage based on assumed leakage rates. The conceptual model discussion provides the background for the modeling approach wherein we focus on simulating transport in the vadose zone, the last potential barrier to CO{sub 2} seepage (Section 4). Because of the potentially wide range of possible properties of actual future geologic sequestration sites, we carry out sensitivity analyses by

  13. Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3‑E1 cells.

    Science.gov (United States)

    Deng, Ang; Zhang, Hongqi; Hu, Minyu; Liu, Shaohua; Gao, Qile; Wang, Yuxiang; Guo, Chaofeng

    2017-12-01

    Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation. In the present study, Ihh was knocked down in osteoblast MC3T3‑E1 cells using short hairpin RNA, to investigate the function of Ihh in osteoblast proliferation and differentiation and to examine the potential mechanism through which Ihh induces osteoblast apoptosis and cell cycle arrest. It was observed that the knockdown of Ihh induced a marked inhibition of cell growth and increased the apoptosis rate compared with the negative control osteoblasts. Downregulation of Ihh resulted in a cell cycle arrest at the G1 to S phase boundary in osteoblasts. In addition, the knockdown of Ihh decreased the alkaline phosphatase activity and mineral deposition of osteoblasts. The inhibitory roles of Ihh downregulation in osteoblast growth and differentiation may be associated with the transforming growth factor‑β/mothers against decapentaplegic homolog and tumor necrosis factor receptor superfamily member 11B/tumor necrosis factor ligand superfamily member 11 signaling pathways. Manipulating either Ihh expression or its signaling components may be of benefit for the treatment of skeletal diseases.

  14. Global patterns of aboveground carbon stock and sequestration in mangroves

    Directory of Open Access Journals (Sweden)

    GUSTAVO C.D. ESTRADA

    Full Text Available ABSTRACT In order to contribute to understand the factors that control the provisioning of the ecosystem service of carbon storage by mangroves, data on carbon stock and sequestration in the aboveground biomass (AGB from 73 articles were averaged and tested for the dependence on latitude, climatic parameters, physiographic types and age. Global means of carbon stock (78.0 ± 64.5 tC.ha-1 and sequestration (2.9 ± 2.2 tC.ha-1.yr-1 showed that mangroves are among the forest ecosystems with greater capacity of carbon storage in AGB per area. On the global scale, carbon stock increases toward the equator (R²=0.22 and is dependent on 13 climatic parameters, which can be integrated in the following predictive equation: Carbon Stock in AGB = -16.342 + (8.341 x Isothermality + (0.021 x Annual Precipitation [R²=0.34; p < 0.05]. It was shown that almost 70% of carbon stock variability is explained by age. Carbon stock and sequestration also vary according to physiographic types, indicating the importance of hydroperiod and edaphic parameters to the local variability of carbon stock. By demonstrating the contribution of local and regional-global factors to carbon stock, this study provides information to the forecast of the effects of future climate changes and local anthropogenic forcings on this ecosystem service.

  15. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng

    2014-12-01

    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  16. A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

    KAUST Repository

    Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

    2014-01-01

    Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

  17. Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma.

    Science.gov (United States)

    Kuromi, Teruyuki; Matsushita, Michiko; Iwasaki, Takeshi; Nonaka, Daisuke; Kuwamoto, Satoshi; Nagata, Keiko; Kato, Masako; Akizuki, Gen; Kitamura, Yukisato; Hayashi, Kazuhiko

    2017-11-01

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. Twenty-nineMCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score. Polymerase chain reaction and sequence analysis for SHH and GLI1 exons were also performed. Expression of SHH was higher in MCPyV-positive MCCs than in MCPyV-negative MCCs (PA. Only 2 mutations with amino acid changes were detected in MCPyV-negative MCCs only: 1 missense mutation in GLI1 exon 4 and 1 nonsense mutation in SHH-3B. Expression of SHH and GLI1 may be useful prognostic markers of MCC because increased expression was associated with better prognosis. The high rate of c.576G>A silent mutation in GLI1 exon 5 was a feature of MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Red cell survival and sequestration in acute intermittent porphyria

    International Nuclear Information System (INIS)

    Nawalkha, P.L.; Soni, S.G.; Agrawal, V.K.; Misra, S.N.

    1980-01-01

    Life span and sequestration of red cells have been studied in twenty one proved cases of acute intermittent porphyria of different age and sex group from Bikaner District, Rajasthan State (India). Chromium-51 labelled red cells were used in the study and the excess count method of Bughe Jones and Szur was used to calculate the index of sequestration. The mean apparent half survival time of erythrocytes in the control subjects was 25.9 +- 2.9 (S.D.) days and the same in the prophyria patients was 27.0 +- 3.8 days. This shows that the life span of red cells is normal in both the patient and the control. Excess destruction of red blood cells was found to take place in either spleen or liver in the disease and no excess accumulation of erythrocytes occurred over spleen as compared to liver. (M.G.B.)

  19. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Flemban, Arwa [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom); Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah 24382 (Saudi Arabia); Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical and Analytical Sciences, Faculty of Health and Applied Sciences, University of West of England, Bristol BS16 1QY (United Kingdom)

    2015-09-16

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT.

  20. The Potential Role of Hedgehog Signaling in the Luminal/Basal Phenotype of Breast Epithelia and in Breast Cancer Invasion and Metastasis

    International Nuclear Information System (INIS)

    Flemban, Arwa; Qualtrough, David

    2015-01-01

    The epithelium of the lactiferous ducts in the breast is comprised of luminal epithelial cells and underlying basal myoepithelial cells. The regulation of cell fate and transit of cells between these two cell types remains poorly understood. This relationship becomes of greater importance when studying the subtypes of epithelial breast carcinoma, which are categorized according to their expression of luminal or basal markers. The epithelial mesenchymal transition (EMT) is a pivotal event in tumor invasion. It is important to understand mechanisms that regulate this process, which bears relation to the normal dynamic of epithelial/basal phenotype regulation in the mammary gland. Understanding this process could provide answers for the regulation of EMT in breast cancer, and thereby identify potential targets for therapy. Evidence points towards a role for hedgehog signaling in breast tissue homeostasis and also in mammary neoplasia. This review examines our current understanding of role of the hedgehog-signaling (Hh) pathway in breast epithelial cells both during breast development and homeostasis and to assess the potential misappropriation of Hh signals in breast neoplasia, cancer stem cells and tumor metastasis via EMT