Sample records for jack caranx hippos

  1. Review of the crevalle jacks, Caranx hippos complex (Teleostei: Carangidae), with a description of a new species from West Africa

    USGS Publications Warehouse

    Smith-Vaniz, W.F.; Carpenter, K.E.

    2007-01-01

    The Caranx hippos species complex comprises three extant species: crevalle jack (Caranx hippos) (Linnaeus, 1766) from both the western and eastern Atlantic oceans; Pacific crevalle jack (Caranx caninus) Gu??nther, 1868 from the eastern Pacific Ocean; and longfin crevalle jack (Caranx fischeri) new species, from the eastern Atlantic, including the Mediterranean Sea and Ascension Island. Adults of all three species are superficially similar with a black blotch on the lower half of the pectoral fin, a black spot on the upper margin of opercle, one or two pairs of enlarged symphyseal canines on the lower jaw, and a similar pattern of breast squamation. Each species has a different pattern of hyperostotic bone development and anal-fin color. The two sympatric eastern Atlantic species also differ from each other in number of dorsal- and anal-fin rays, and in large adults of C. fischeri the lobes of these fins are longer and the body is deeper. Caranx hippos from opposite sides of the Atlantic are virtually indistinguishable externally but differ consistently in the expression of hyperostosis of the first dorsal-fin pterygiophore. The fossil species Caranx carangopsis Steindachner 1859 appears to have been based on composite material of Trachurus sp. and a fourth species of the Caranx hippos complex. Patterns of hyperostotic bone development are compared in the nine (of 15 total) species of Caranx sensu stricto that exhibit hyperostosis.

  2. Population structure and comparative phylogeography of jack species (Caranx ignobilis and C. melampygus) in the high Hawaiian Islands.

    PubMed

    Santos, Scott R; Xiang, Yu; Tagawa, Annette W

    2011-01-01

    Members of the family Carangidae are top-level predators and highly prized food and sport fishes. Although ecologically and economically important, little is known about the biology of numerous species in the family. This is particularly true of the jacks Caranx ignobilis and C. melampygus, which have experienced recent population reductions around the high Hawaiian Islands due to overfishing. Previous studies have documented territorial tendencies as well as cases of long-distance excursions in both species, suggesting populations may exhibit a range of structure at the genetic level. To explore this possibility, mitochondrial DNA ATPase6 and ATPase8 gene sequence variation was assessed from 91 individuals (33 C. ignobilis and 58 C. melampygus) spanning the islands of Kaua'i, O'ahu, Moloka'i, Maui, and Hawai'i. Although a total of 20 distinct haplotypes (8 for C. ignobilis; 12 for C. melampygus) were recovered, no evidence of population structure was found for either species across the examined geographic range. However, distinct demographic patterns were identified, implying differing evolutionary histories and/or population dynamics. Additionally, ∼ 6% of the examined C. ignobilis were C. ignobilis × C. melampygus hybrids because they harbored mitochondrial haplotypes typical of C. melampygus. These hybrids contribute to measurable gene flow between the species and may play a significant role in the evolution of the genus.

  3. Species-specific patterns of hyperostosis in marine teleost fishes

    USGS Publications Warehouse

    Smith-Vaniz, William F.; Kaufman, L.S.; Glowacki, J.

    1995-01-01

    The occurrence of swollen or hyperostotic bones in skeletal preparations, preserved museum material or whole fresh specimens of marine teleost fishes was identified in 92 species belonging to 22 families. Patterns of hyperostotic skeletal growth were typically consistent and often species-specific in all individuals larger than a certain size. The taxonomic distribution of hyperostosis in diverse phylogenetic groups suggests that it has arisen independently many times. Selected bones from two species of the family Carangidae, horse-eye jack Caranx latus Agassiz and crevalle jackCaranx hippos (Linnaeus), were examined in detail by light and electron microscopy. Nonhyperostotic bone contained osteoid-producing osteoblasts, resorbing osteoclasts, occasional osteocytes, and a rich vascular network, all characteristics of cellular bone. Thus, these fishes have a spatial juxtaposition of cellular and acellular bone tissues in adjacent and often serially homologous bone sites. The functional significance of hyperostosis is unknown, but it is a predictable manifestation of bone growth and development for the many taxa in which it occurs.

  4. 50 CFR 665.101 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... palu-gutusiliva red snapper, silvermouth Aphareus rutilans. asoama gray snapper, jobfish Aprion virescens. sapoanae giant trevally, jack Caranx ignobilis. tafauli black trevally, jack Caranx lugubris. fausi blacktip grouper Epinephelus fasciatus. papa, velo lunartail grouper Variola louti. palu malau red...

  5. 50 CFR 665.101 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... palu-gutusiliva red snapper, silvermouth Aphareus rutilans. asoama gray snapper, jobfish Aprion virescens. sapoanae giant trevally, jack Caranx ignobilis. tafauli black trevally, jack Caranx lugubris. fausi blacktip grouper Epinephelus fasciatus. papa, velo lunartail grouper Variola louti. palu malau red...

  6. 50 CFR 665.101 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... palu-gutusiliva red snapper, silvermouth Aphareus rutilans. asoama gray snapper, jobfish Aprion virescens. sapoanae giant trevally, jack Caranx ignobilis. tafauli black trevally, jack Caranx lugubris. fausi blacktip grouper Epinephelus fasciatus. papa, velo lunartail grouper Variola louti. palu malau red...

  7. 50 CFR 665.101 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... palu-gutusiliva red snapper, silvermouth Aphareus rutilans. asoama gray snapper, jobfish Aprion virescens. sapoanae giant trevally, jack Caranx ignobilis. tafauli black trevally, jack Caranx lugubris. fausi blacktip grouper Epinephelus fasciatus. papa, velo lunartail grouper Variola louti. palu malau red...

  8. Hippo vs. Crab: tissue-specific functions of the mammalian Hippo pathway.

    PubMed

    Nishio, Miki; Maehama, Tomohiko; Goto, Hiroki; Nakatani, Keisuke; Kato, Wakako; Omori, Hirofumi; Miyachi, Yosuke; Togashi, Hideru; Shimono, Yohei; Suzuki, Akira

    2017-01-01

    The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements. In this review, we attempt to systematically summarize results that have been gleaned from detailed in vivo characterizations of these mutants. Our goal is to describe the physiological roles of Hippo signaling in several normal organ systems, as well as to emphasize how disruption of the Hippo pathway, and particularly hyperactivation of YAP1/TAZ, can be oncogenic. © 2017 The Authors Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  9. Two faces of Hippo: activate or suppress the Hippo pathway in cancer.

    PubMed

    Cao, Jingwen; Huang, Wenlong

    2017-11-01

    The Hippo pathway has generated considerable interest in recent years because of its involvement in several key hallmarks of cancer progression and metastasis. Research on the Hippo signaling pathway in cancer has been used to determine the activity of yes-associated protein (YAP) in tumorigenesis and disease progression. Previous studies have shown that the Hippo pathway can be used as a target to inhibit YAP activity and is a viable treatment for cancer. However, more studies are required to further advance our understanding of the Hippo signaling pathway in cancer. It has been shown that knockout of serine/threonine-kinases LATS1/2 in the Hippo pathway suppresses cancer immunity in mice. In addition, suppression of the oncogene YAP could contribute toward cancer immune therapy. Therefore, regulation of Hippo signaling can be an attractive alternative strategy for cancer treatment. This review will provide a summary of currently known compounds that activate or suppress the Hippo pathway.

  10. Disease implication of hyper-Hippo signalling.

    PubMed

    Wang, Shu-Ping; Wang, Lan-Hsin

    2016-10-01

    The Hippo signalling pathway regulates cellular proliferation, apoptosis and differentiation, thus exerting profound effects on cellular homeostasis. Inhibition of Hippo signalling has been frequently implicated in human cancers, indicating a well-known tumour suppressor function of the Hippo pathway. However, it is less certain whether and how hyperactivation of the Hippo pathway affects biological outcome in living cells. This review describes current knowledge of the regulatory mechanisms of the Hippo pathway, mainly focusing on hyperactivation of the Hippo signalling nexus. The disease implications of hyperactivated Hippo signalling have also been discussed, including arrhythmogenic cardiomyopathy, Sveinsson's chorioretinal atrophy, Alzheimer's disease, amyotrophic lateral sclerosis and diabetes. By highlighting the significance of disease-relevant Hippo signalling activation, this review can offer exciting prospects to address the onset and potential reversal of Hippo-related disorders. © 2016 The Authors.

  11. Disease implication of hyper-Hippo signalling

    PubMed Central

    Wang, Shu-Ping

    2016-01-01

    The Hippo signalling pathway regulates cellular proliferation, apoptosis and differentiation, thus exerting profound effects on cellular homeostasis. Inhibition of Hippo signalling has been frequently implicated in human cancers, indicating a well-known tumour suppressor function of the Hippo pathway. However, it is less certain whether and how hyperactivation of the Hippo pathway affects biological outcome in living cells. This review describes current knowledge of the regulatory mechanisms of the Hippo pathway, mainly focusing on hyperactivation of the Hippo signalling nexus. The disease implications of hyperactivated Hippo signalling have also been discussed, including arrhythmogenic cardiomyopathy, Sveinsson's chorioretinal atrophy, Alzheimer's disease, amyotrophic lateral sclerosis and diabetes. By highlighting the significance of disease-relevant Hippo signalling activation, this review can offer exciting prospects to address the onset and potential reversal of Hippo-related disorders. PMID:27805903

  12. 50 CFR 665.201 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Caranx ignobilis. ulua la`uli black jack Caranx lugubris. hpu`upu`u sea bass Epinephalus quernus... dumerili. Hawaii restricted bottomfish species fishing year means the year beginning at 0001 HST on... is used in any non-commercial vessel-based fishing, landing, or transshipment of any Hawaii...

  13. 50 CFR 665.201 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Caranx ignobilis. ulua la`uli black jack Caranx lugubris. hpu`upu`u sea bass Epinephalus quernus... dumerili. Hawaii restricted bottomfish species fishing year means the year beginning at 0001 HST on... is used in any non-commercial vessel-based fishing, landing, or transshipment of any Hawaii...

  14. 50 CFR 665.201 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Caranx ignobilis. ulua la`uli black jack Caranx lugubris. hpu`upu`u sea bass Epinephalus quernus... dumerili. Hawaii restricted bottomfish species fishing year means the year beginning at 0001 HST on... is used in any non-commercial vessel-based fishing, landing, or transshipment of any Hawaii...

  15. 50 CFR 665.201 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Caranx ignobilis. ulua la`uli black jack Caranx lugubris. hpu`upu`u sea bass Epinephalus quernus... dumerili. Hawaii restricted bottomfish species fishing year means the year beginning at 0001 HST on... is used in any non-commercial vessel-based fishing, landing, or transshipment of any Hawaii...

  16. 50 CFR 665.201 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Caranx ignobilis. ulua la`uli black jack Caranx lugubris. hpu`upu`u sea bass Epinephalus quernus... dumerili. Hawaii restricted bottomfish species fishing year means the year beginning at 0001 HST on... is used in any non-commercial vessel-based fishing, landing, or transshipment of any Hawaii...

  17. Mechanisms of Hippo pathway regulation

    PubMed Central

    Meng, Zhipeng; Moroishi, Toshiro; Guan, Kun-Liang

    2016-01-01

    The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway. PMID:26728553

  18. The Hippo Pathway: Immunity and Cancer.

    PubMed

    Taha, Zaid; J Janse van Rensburg, Helena; Yang, Xiaolong

    2018-03-28

    Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work.

  19. The Hippo Pathway: Immunity and Cancer

    PubMed Central

    J. Janse van Rensburg, Helena

    2018-01-01

    Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats. We further discuss how Hippo signaling functions as part of an immune response. Finally, we review how immune cell-intrinsic Hippo signaling modulates the development/function of leukocytes and propose directions for future work. PMID:29597279

  20. AJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol

    PubMed Central

    Jagannathan, Radhika; Schimizzi, Gregory V.; Zhang, Kun; Loza, Andrew J.; Yabuta, Norikazu; Nojima, Hitoshi

    2016-01-01

    The Hippo pathway controls organ growth and is implicated in cancer development. Whether and how Hippo pathway activity is limited to sustain or initiate cell growth when needed is not understood. The members of the AJUBA family of LIM proteins are negative regulators of the Hippo pathway. In mammalian epithelial cells, we found that AJUBA LIM proteins limit Hippo regulation of YAP, in proliferating cells only, by sequestering a cytosolic Hippo kinase complex in which LATS kinase is inhibited. At the plasma membranes of growth-arrested cells, AJUBA LIM proteins do not inhibit or associate with the Hippo kinase complex. The ability of AJUBA LIM proteins to inhibit YAP regulation by Hippo and to associate with the kinase complex directly correlate with their capacity to limit Hippo signaling during Drosophila wing development. AJUBA LIM proteins did not influence YAP activity in response to cell-extrinsic or cell-intrinsic mechanical signals. Thus, AJUBA LIM proteins limit Hippo pathway activity in contexts where cell proliferation is needed. PMID:27457617

  1. AJUBA LIM Proteins Limit Hippo Activity in Proliferating Cells by Sequestering the Hippo Core Kinase Complex in the Cytosol.

    PubMed

    Jagannathan, Radhika; Schimizzi, Gregory V; Zhang, Kun; Loza, Andrew J; Yabuta, Norikazu; Nojima, Hitoshi; Longmore, Gregory D

    2016-10-15

    The Hippo pathway controls organ growth and is implicated in cancer development. Whether and how Hippo pathway activity is limited to sustain or initiate cell growth when needed is not understood. The members of the AJUBA family of LIM proteins are negative regulators of the Hippo pathway. In mammalian epithelial cells, we found that AJUBA LIM proteins limit Hippo regulation of YAP, in proliferating cells only, by sequestering a cytosolic Hippo kinase complex in which LATS kinase is inhibited. At the plasma membranes of growth-arrested cells, AJUBA LIM proteins do not inhibit or associate with the Hippo kinase complex. The ability of AJUBA LIM proteins to inhibit YAP regulation by Hippo and to associate with the kinase complex directly correlate with their capacity to limit Hippo signaling during Drosophila wing development. AJUBA LIM proteins did not influence YAP activity in response to cell-extrinsic or cell-intrinsic mechanical signals. Thus, AJUBA LIM proteins limit Hippo pathway activity in contexts where cell proliferation is needed. Copyright © 2016 Jagannathan et al.

  2. Hippo signaling impedes adult heart regeneration

    PubMed Central

    Heallen, Todd; Morikawa, Yuka; Leach, John; Tao, Ge; Willerson, James T.; Johnson, Randy L.; Martin, James F.

    2013-01-01

    Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control pathway, is a kinase cascade that inhibits developing cardiomyocyte proliferation but it has not been studied postnatally or in fully mature adult cardiomyocytes. Here, we investigated Hippo signaling in adult cardiomyocyte renewal and regeneration. We found that unstressed Hippo-deficient adult mouse cardiomyocytes re-enter the cell cycle and undergo cytokinesis. Moreover, Hippo deficiency enhances cardiomyocyte regeneration with functional recovery after adult myocardial infarction as well as after postnatal day eight (P8) cardiac apex resection and P8 myocardial infarction. In damaged hearts, Hippo mutant cardiomyocytes also have elevated proliferation. Our findings reveal that Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration. Targeting the Hippo pathway in human disease might be beneficial for the treatment of heart disease. PMID:24255096

  3. Premetazoan origin of the Hippo signaling pathway

    PubMed Central

    Sebé-Pedrós, Arnau; Zheng, Yonggang; Ruiz-Trillo, Iñaki; Pan, Duojia

    2012-01-01

    Summary Non-aggregative multicellularity requires strict control of cell number. The Hippo signaling pathway coordinates cell proliferation and apoptosis and is a central regulator of organ size in animals. Recent studies have shown the presence of key members of the Hippo pathway in non-bilaterian animals, but failed to identify this pathway outside Metazoa. Through comparative analyses of recently sequenced holozoan genomes, we show that Hippo pathway components, such as the kinases Hippo and Warts, the co-activator Yorkie and the transcription factor Scalloped, were already present in the unicellular ancestors of animals. Remarkably, functional analysis of Hippo components of the amoeboid holozoan Capsaspora owczarzaki, performed in Drosophila, demonstrate that the growth-regulatory activity of the Hippo pathway is conserved in this unicellular lineage. Our findings show that the Hippo pathway evolved well before the origin of Metazoa and highlight the importance of Hippo signaling as a key developmental mechanism pre-dating the origin of Metazoa. PMID:22832104

  4. Targeting the Hippo signalling pathway for cancer treatment.

    PubMed

    Nakatani, Keisuke; Maehama, Tomohiko; Nishio, Miki; Goto, Hiroki; Kato, Wakako; Omori, Hirofumi; Miyachi, Yosuke; Togashi, Hideru; Shimono, Yohei; Suzuki, Akira

    2017-03-01

    The Hippo signalling pathway monitors cell-cell contact and external factors that shape tissue structure. In mice, tumourigenesis and developmental abnormalities are common consequences of dysregulated Hippo signalling. Expression of Hippo pathway components is also frequently altered in human tumours and correlates with poor prognosis and reduced patient survival. Thus, the Hippo pathway is an attractive anti-cancer target. Here, we provide an overview of the function and regulation of Hippo signalling components and summarize progress to date on the development of agents able to regulate Hippo signalling for cancer therapy. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  5. Regulation of Hippo signalling by p38 signalling

    PubMed Central

    Huang, Dashun; Li, Xiaojiao; Sun, Li; Huang, Ping; Ying, Hao; Wang, Hui; Wu, Jiarui; Song, Haiyun

    2016-01-01

    The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we identify the p38 mitogen-activated protein kinase (MAPK) pathway as a new upstream branch of the Hippo pathway. In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression. Loss-of-function studies show that lic regulates Hippo signalling in ovary follicle cells and in the wing disc. Epistasis analysis indicates that Mekk1 and lic affect Hippo signalling via p38b and wts. We further demonstrate that the Mekk1-Lic-p38b cascade inhibits Hippo signalling by promoting F-actin accumulation and Jub phosphorylation. In addition, p38 signalling modulates actin filaments and Hippo signalling in parallel to small GTPases Ras, Rac1, and Rho1. Lastly, we show that p38 signalling regulates Hippo signalling in mammalian cell lines. The Lic homologue MKK3 promotes nuclear localization of YAP via the actin cytoskeleton. Upregulation or downregulation of the p38 pathway regulates YAP-mediated transcription. Our work thus reveals a conserved crosstalk between the p38 MAPK pathway and the Hippo pathway in growth regulation. PMID:27402810

  6. Role of Hippo signaling in regulating immunity.

    PubMed

    Hong, Lixin; Li, Xun; Zhou, Dawang; Geng, Jing; Chen, Lanfen

    2018-03-22

    The Hippo signaling pathway has been established as a key regulator of organ size control, tumor suppression, and tissue regeneration in multiple organisms. Recently, emerging evidence has indicated that Hippo signaling might play an important role in regulating the immune system in both Drosophila and mammals. In particular, patients bearing a loss-of-function mutation of MST1 are reported to have an autosomal recessive primary immunodeficiency syndrome. MST1/2 kinases, the mammalian orthologs of Drosophila Hippo, may activate the non-canonical Hippo signaling pathway via MOB1A/B and/or NDR1/2 or cross-talk with other essential signaling pathways to regulate both innate and adaptive immunity. In this review, we present and discuss recent findings of cellular mechanisms/functions of Hippo signaling in the innate immunity in Drosophila and in mammals, T cell immunity, as well as the implications of Hippo signaling for tumor immunity.

  7. Regulation of Hippo signalling by p38 signalling.

    PubMed

    Huang, Dashun; Li, Xiaojiao; Sun, Li; Huang, Ping; Ying, Hao; Wang, Hui; Wu, Jiarui; Song, Haiyun

    2016-08-01

    The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we identify the p38 mitogen-activated protein kinase (MAPK) pathway as a new upstream branch of the Hippo pathway. In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression. Loss-of-function studies show that lic regulates Hippo signalling in ovary follicle cells and in the wing disc. Epistasis analysis indicates that Mekk1 and lic affect Hippo signalling via p38b and wts We further demonstrate that the Mekk1-Lic-p38b cascade inhibits Hippo signalling by promoting F-actin accumulation and Jub phosphorylation. In addition, p38 signalling modulates actin filaments and Hippo signalling in parallel to small GTPases Ras, Rac1, and Rho1. Lastly, we show that p38 signalling regulates Hippo signalling in mammalian cell lines. The Lic homologue MKK3 promotes nuclear localization of YAP via the actin cytoskeleton. Upregulation or downregulation of the p38 pathway regulates YAP-mediated transcription. Our work thus reveals a conserved crosstalk between the p38 MAPK pathway and the Hippo pathway in growth regulation. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  8. The Hippo pathway regulates human megakaryocytic differentiation.

    PubMed

    Lorthongpanich, Chanchao; Jiamvoraphong, Nittaya; Supraditaporn, Kantpitchar; Klaihmon, Phatchanat; U-Pratya, Yaowalak; Issaragrisil, Surapol

    2017-01-05

    The Hippo pathway is involved in several biological processes in both flies and mammals. Recent studies have shown that the Hippo pathway regulates Drosophila's haematopoiesis; however, understanding of its role in mammalian haematopoiesis is still limited. In flies, deletion of the Hippo component gene, Warts, affects crystal cell differentiation. We explored the role of the Hippo pathway in human haematopoiesis focusing on megakaryopoiesis. To investigate the role of LATS1/2 (a mammalian homolog of Warts) in human megakaryoblastic cell differentiation and platelet formation, megakaryoblastic cell (MEG-01) line was used as a model to gain insight into mechanism of the Hippo pathway in mammalian megakaryopoiesis. Effect of LATS1/2 on megakaryoblastic cell differentiation and platelet production were determined by functional changes. We found that depletion of LATS1/2 resulted in an increase of CD41 + megakaryocytes with impaired platelet biogenesis. Our study shows that the Hippo signalling pathway plays a crucial role in human megakaryoblastic cell differentiation and thrombopoiesis.

  9. Hippo signaling promotes JNK-dependent cell migration.

    PubMed

    Ma, Xianjue; Wang, Hongxiang; Ji, Jiansong; Xu, Wenyan; Sun, Yihao; Li, Wenzhe; Zhang, Xiaoping; Chen, Juxiang; Xue, Lei

    2017-02-21

    Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition through JNK, as inhibition of JNK signaling dramatically blocked Hippo pathway activation-induced matrix metalloproteinase 1 expression and cell invasion. Furthermore, we identify bantam -Rox8 modules as essential components downstream of Yorkie in mediating JNK-dependent cell invasion. Finally, we confirm that YAP (Yes-associated protein) expression negatively regulates TIA1 (Rox8 ortholog) expression and cell invasion in human cancer cells. Together, these findings provide molecular insights into Hippo pathway-mediated cell invasion and also raise a noteworthy concern in therapeutic interventions of Hippo-related cancers, as simply inhibiting Yorkie or YAP activity might paradoxically accelerate cell invasion and metastasis.

  10. Characterization of Hippo Pathway Components by Gene Inactivation.

    PubMed

    Plouffe, Steven W; Meng, Zhipeng; Lin, Kimberly C; Lin, Brian; Hong, Audrey W; Chun, Justin V; Guan, Kun-Liang

    2016-12-01

    The Hippo pathway is important for regulating tissue homeostasis, and its dysregulation has been implicated in human cancer. However, it is not well understood how the Hippo pathway becomes dysregulated because few mutations in core Hippo pathway components have been identified. Therefore, much work in the Hippo field has focused on identifying upstream regulators, and a complex Hippo interactome has been identified. Nevertheless, it is not always clear which components are the most physiologically relevant in regulating YAP/TAZ. To provide an overview of important Hippo pathway components, we created knockout cell lines for many of these components and compared their relative contributions to YAP/TAZ regulation in response to a wide range of physiological signals. By this approach, we provide an overview of the functional importance of many Hippo pathway components and demonstrate NF2 and RHOA as important regulators of YAP/TAZ and TAOK1/3 as direct kinases for LATS1/2. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Molecular Pathways: Hippo Signaling, a Critical Tumor Suppressor.

    PubMed

    Sebio, Ana; Lenz, Heinz-Josef

    2015-11-15

    The Salvador-Warts-Hippo pathway controls cell fate and tissue growth. The main function of the Hippo pathway is to prevent YAP and TAZ translocation to the nucleus where they induce the transcription of genes involved in cell proliferation, survival, and stem cell maintenance. Hippo signaling is, thus, a complex tumor suppressor, and its deregulation is a key feature in many cancers. Recent mounting evidence suggests that the overexpression of Hippo components can be useful prognostic biomarkers. Moreover, Hippo signaling appears to be intimately linked to some of the most important signaling pathways involved in cancer development and progression. A better understanding of the Hippo pathway is thus essential to untangle tumor biology and to develop novel anticancer therapies. Here, we comment on the progress made in understanding Hippo signaling and its connections, and also on how new drugs modulating this pathway, such as Verteporfin and C19, are highly promising cancer therapeutics. ©2015 American Association for Cancer Research.

  12. The Hippo pathway: regulators and regulations

    PubMed Central

    Yu, Fa-Xing; Guan, Kun-Liang

    2013-01-01

    Control of cell number is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation or organ degeneration. The Hippo pathway in both Drosophila and mammals regulates cell number by modulating cell proliferation, cell death, and cell differentiation. Recently, numerous upstream components involved in the Hippo pathway have been identified, such as cell polarity, mechanotransduction, and G-protein-coupled receptor (GPCR) signaling. Actin cytoskeleton or cellular tension appears to be the master mediator that integrates and transmits upstream signals to the core Hippo signaling cascade. Here, we review regulatory mechanisms of the Hippo pathway and discuss potential implications involved in different physiological and pathological conditions. PMID:23431053

  13. Hippo signaling: growth control and beyond

    PubMed Central

    Halder, Georg; Johnson, Randy L.

    2011-01-01

    The Hippo pathway has emerged as a conserved signaling pathway that is essential for the proper regulation of organ growth in Drosophila and vertebrates. Although the mechanisms of signal transduction of the core kinases Hippo/Mst and Warts/Lats are relatively well understood, less is known about the upstream inputs of the pathway and about the downstream cellular and developmental outputs. Here, we review recently discovered mechanisms that contribute to the dynamic regulation of Hippo signaling during Drosophila and vertebrate development. We also discuss the expanding diversity of Hippo signaling functions during development, discoveries that shed light on a complex regulatory system and provide exciting new insights into the elusive mechanisms that regulate organ growth and regeneration. PMID:21138973

  14. The Hippo pathway in intestinal regeneration and disease.

    PubMed

    Hong, Audrey W; Meng, Zhipeng; Guan, Kun-Liang

    2016-06-01

    The Hippo pathway is a signalling cascade conserved from Drosophila melanogaster to mammals. The mammalian core kinase components comprise MST1 and MST2, SAV1, LATS1 and LATS2 and MOB1A and MOB1B. The transcriptional co-activators YAP1 and TAZ are the downstream effectors of the Hippo pathway and regulate target gene expression. Hippo signalling has crucial roles in the control of organ size, tissue homeostasis and regeneration, and dysregulation of the Hippo pathway can lead to uncontrolled cell growth and malignant transformation. Mammalian intestine consists of a stem cell compartment as well as differentiated cells, and its ability to regenerate rapidly after injury makes it an excellent model system to study tissue homeostasis, regeneration and tumorigenesis. Several studies have established the important role of the Hippo pathway in these processes. In addition, crosstalk between Hippo and other signalling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this Review, we summarize studies on the role of the Hippo pathway in the intestine on these physiological processes and the underlying mechanisms responsible, and discuss future research directions and potential therapeutic strategies targeting Hippo signalling in intestinal disease.

  15. The Hippo pathway in intestinal regeneration and disease

    PubMed Central

    Hong, Audrey W.; Meng, Zhipeng; Guan, Kun-Liang

    2017-01-01

    The Hippo pathway is a signalling cascade conserved from Drosophila melanogaster to mammals. The mammalian core kinase components comprise MST1 and MST2, SAV1, LATS1 and LATS2 and MOB1A and MOB1B. The transcriptional co-activators YAP1 and TAZ are the downstream effectors of the Hippo pathway and regulate target gene expression. Hippo signalling has crucial roles in the control of organ size, tissue homeostasis and regeneration, and dysregulation of the Hippo pathway can lead to uncontrolled cell growth and malignant transformation. Mammalian intestine consists of a stem cell compartment as well as differentiated cells, and its ability to regenerate rapidly after injury makes it an excellent model system to study tissue homeostasis, regeneration and tumorigenesis. Several studies have established the important role of the Hippo pathway in these processes. In addition, crosstalk between Hippo and other signalling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this Review, we summarize studies on the role of the Hippo pathway in the intestine on these physiological processes and the underlying mechanisms responsible, and discuss future research directions and potential therapeutic strategies targeting Hippo signalling in intestinal disease. PMID:27147489

  16. Molecular mechanisms of the mammalian Hippo signaling pathway.

    PubMed

    Ji, Xin-yan; Zhong, Guoxuan; Zhao, Bin

    2017-07-20

    The Hippo pathway plays an evolutionarily conserved fundamental role in controlling organ size in multicellular organisms. Importantly, evidence from studies of patient samples and mouse models clearly indicates that deregulation of the Hippo signaling pathway plays a crucial role in the initiation and progression of many different types of human cancers. The Hippo signaling pathway is regulated by various stimuli, such as mechanical stress, G-protein coupled receptor signaling, and cellular energy status. When activated, the Hippo kinase cascade phosphorylates and inhibits the transcription co-activator YAP (Yes-associated protein), and its paralog TAZ (transcriptional coactivator with PDZ-binding motif), resulting in their cytoplasmic retention and degradation. When the Hippo signaling pathway is inactive, dephosphorylated YAP/TAZ translocate into the nucleus and activate gene transcription through binding to TEAD (TEA domain) family and other transcription factors. Such changes in gene expression promote cell proliferation and stem cell/progenitor cell self-renewal but inhibit apoptosis, thereby coordinately promote increase in organ size, tissue regeneration, and tumorigenesis. In this review, we summarize the molecular mechanisms of the mammalian Hippo signaling pathway with special emphasis on the Hippo kinase cascade and its upstream signals, the Hippo signaling pathway regulation of YAP and the mechanisms of YAP in regulation of gene transcription.

  17. Upstream paths for Hippo signaling in Drosophila organ development.

    PubMed

    Choi, Kwang-Wook

    2018-03-01

    Organ growth is fundamental to animal development. One of major mechanisms for growth control is mediated by the conserved Hippo signaling pathway initially identified in Drosophila. The core of this pathway in Drosophila consists of a cascade of protein kinases Hippo and Warts that negatively regulate transcriptional coactivator Yorkie (Yki). Activation of Yki promotes cell survival and proliferation to induce organ growth. A key issue in Hippo signaling is to understand how core kinase cascade is activated. Activation of Hippo kinase cascade is regulated in the upstream by at least two transmembrane proteins Crumbs and Fat that act in parallel. These membrane proteins interact with additional factors such as FERM-domain proteins Expanded and Merlin to modulate subcellular localization and function of the Hippo kinase cascade. Hippo signaling is also influenced by cytoskeletal networks and cell tension in epithelia of developing organs. These upstream events in the regulation of Hippo signaling are only partially understood. This review focuses on our current understanding of some upstream processes involved in Hippo signaling in developing Drosophila organs. [BMB Reports 2018; 51(3): 134-142].

  18. Hippo signaling: Special issue of BMB Reports in 2018.

    PubMed

    Jho, Eek-Hoon

    2018-03-01

    Since the first component of Hippo signaling, Wts in Drosophila, was identified in 1995, the progress of Hippo signaling studies has been very slow initially. However, after the findings suggesting that the core kinase pathway established in Drosophila was evolutionarily conserved in metazoans for the determination of organ size around 2008, the number of publications related to Hippo signaling has grown exponentially. Identification of molecular mechanisms underlying Hippo signaling response to intrinsic cues, such as cell-cell contact and mechanotransduction, as well as extrinsic cues, such as nutrients and soluble factors, has been one of the key topics of Hippo signaling. In the beginning, the role of Hippo signaling in the regulation of cell proliferation, organ size determination and tumorigenesis was mainly studied. However, the study of Hippo signaling expanded recently to unexpected biological phenomena such as tissue regeneration, innate immunity and miRNA biogenesis. Editors of BMB reports thought that it was timely and informative to review the status of Hippo signaling to introduce the topic to researchers outside of this field. As an editor of BMB reports, I invited seven researchers, who are currently working in Korea on different aspects of Hippo signaling, to submit minireviews. [BMB Reports 2018; 51(3): 105].

  19. Disease implications of the Hippo/YAP pathway

    PubMed Central

    Plouffe, Steven W; Hong, Audrey W; Guan, Kun-Liang

    2015-01-01

    The Hippo signaling pathway is important for controlling organ size and tissue homeostasis. Originally identified in Drosophila melanogaster, the core components of the Hippo pathway are highly conserved in mammals. The Hippo pathway can be modulated by a wide range of stimuli, including G protein coupled receptor (GPCR) signaling, changes in the actin cytoskeleton, cell-cell contact, and cell polarity. When activated, the Hippo pathway functions as a tumor suppressor to limit cell growth. However, dysregulation by genetic inactivation of core pathway components, or amplification or gene fusion of its downstream effectors, results in increased cell proliferation and decreased apoptosis and differentiation. Not surprisingly, this can lead to tissue overgrowth, tumorigenesis, and many other diseases. PMID:25702974

  20. Hippo Signaling Regulates Pancreas Development through Inactivation of Yap

    PubMed Central

    Day, Caroline E.; Boerner, Brian P.; Johnson, Randy L.; Sarvetnick, Nora E.

    2012-01-01

    The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition, and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo kinase cascade is a critical regulator of organ growth. To investigate the role of Hippo signaling in pancreas biology, we deleted Hippo pathway components in the developing mouse pancreas. Unexpectedly, the pancreas from Hippo-deficient offspring was reduced in size, with defects evident throughout the organ. Increases in the dephosphorylated nuclear form of Yap are apparent throughout the exocrine compartment and correlate with increases in levels of cell proliferation. However, the mutant exocrine tissue displays extensive disorganization leading to pancreatitis-like autodigestion. Interestingly, our results suggest that Hippo signaling does not directly regulate the pancreas endocrine compartment as Yap expression is lost following endocrine specification through a Hippo-independent mechanism. Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ. PMID:23071096

  1. The Hippo signal transduction pathway in soft tissue sarcomas.

    PubMed

    Mohamed, Abdalla D; Tremblay, Annie M; Murray, Graeme I; Wackerhage, Henning

    2015-08-01

    Sarcomas are rare cancers (≈1% of all solid tumours) usually of mesenchymal origin. Here, we review evidence implicating the Hippo pathway in soft tissue sarcomas. Several transgenic mouse models of Hippo pathway members (Nf2, Mob1, LATS1 and YAP1 mutants) develop various types of sarcoma. Despite that, Hippo member genes are rarely point mutated in human sarcomas. Instead, WWTR1-CAMTA1 and YAP1-TFE3 fusion genes are found in almost all cases of epithelioid haemangioendothelioma. Also copy number gains of YAP1 and other Hippo members occur at low frequencies but the most likely cause of perturbed Hippo signalling in sarcoma is the cross-talk with commonly mutated cancer genes such as KRAS, PIK3CA, CTNNB1 or FBXW7. Current Hippo pathway-targeting drugs include compounds that target the interaction between YAP and TEAD G protein-coupled receptors (GPCR) and the mevalonate pathway (e.g. statins). Given that many Hippo pathway-modulating drugs are already used in patients, this could lead to early clinical trials testing their efficacy in different types of sarcoma. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  2. Hippo signaling pathway in cardiovascular development and diseases.

    PubMed

    Wang, Yong-yu; Yu, Wei; Zhou, Bin

    2017-07-20

    Cardiovascular diseases have become the leading cause of death in the world. Understanding the development of cardiovascular system and the pathogenesis of cardiovascular diseases will promote the generation of novel preventive and therapeutic strategy. The Hippo pathway is a recently identified signaling cascade that plays a critical role in organ size control, cell proliferation, apoptosis and fate determination of stem cells. Gene knockout and transgenic mouse models have revealed that the Hippo signaling pathway is involved in heart development, cardiomyocyte proliferation, apoptosis, hypertrophy and cardiac regeneration. The Hippo signaling pathway also regulates vascular development, differentiation and various functions of vascular cells. Dysregulation of the Hippo signaling pathway leads to different kinds of cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy, neointima formation and atherosclerosis. In this review, we briefly summarize current research on the roles and regulation mechanisms of the Hippo signaling pathway in cardiovascular development and diseases.

  3. Emerging role of Hippo signalling pathway in bladder cancer.

    PubMed

    Xia, Jianling; Zeng, Ming; Zhu, Hua; Chen, Xiangjian; Weng, Zhiliang; Li, Shi

    2018-01-01

    Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co-effectors YAP1/TAZ. The core components of the Hippo pathway, which induce BC stemness acquisition, metastasis and chemoresistance, will be emphasized. Additional research on the Hippo pathway will advance our understanding of the mechanism of BC as well as the development and progression of other cancers and may be exploited therapeutically. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  4. POSH regulates Hippo signaling through ubiquitin-mediated expanded degradation.

    PubMed

    Ma, Xianjue; Guo, Xiaowei; Richardson, Helena E; Xu, Tian; Xue, Lei

    2018-02-27

    The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in Drosophila POSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes. Furthermore, knockdown of POSH impedes dextran sulfate sodium-induced Yorkie-dependent intestinal stem cell renewal, suggesting a physiological role of POSH in modulating Hippo signaling. Mechanistically, POSH binds to the C-terminal of Ex and is essential for the Crumbs-induced ubiquitination and degradation of Ex. Our findings establish POSH as a crucial regulator that integrates the signal from the cell surface to negatively regulate Ex-mediated Hippo activation in Drosophila .

  5. The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment

    PubMed Central

    Johnson, Randy; Halder, Georg

    2014-01-01

    The Hippo signaling pathway is an emerging growth control and tumor suppressor pathway that regulates cell proliferation and stem cell functions. Defects in Hippo signaling and hyperactivation of its downstream effectors YAP and TAZ contribute to the development of cancer, suggesting that pharmacological inhibition of YAP and TAZ activity may be an effective anticancer strategy. Conversely, YAP and TAZ can also play beneficial roles in stimulating tissue repair and regeneration following injury, therefore activation of YAP and TAZ may be useful in these contexts. Recently, a complex network of intracellular and extracellular signaling pathways that modulate YAP and TAZ activities have been identified. Here we review the regulation of the Hippo signaling pathway, its functions in normal homeostasis and disease, and recent progress in the identification of small molecule pathway modulators. PMID:24336504

  6. The dark side of hippo signaling: A cancer promoter role.

    PubMed

    Dunn, Brandon; Ma, Xianjue

    2017-10-02

    The Hippo signaling pathway regulates organ size and tissue homeostasis. Given this role it is unsurprising that dysregulation of this pathway has implications for cancer progression. A convincing body of literature shows that the Hippo pathway serves a tumor suppressive function with its inactivation leading to massive overgrowth. However, additional studies have also shown that activation of Hippo signaling can promote tumor progression. It remains unknown how a single pathway can produce such diametrically opposed effects. This lack of knowledge is in part due to our inability to make meaningful comparisons from studies which have taken place in a variety of cell types, tissues, and organisms. Recently however, we have published 2 studies using the Drosophila wing disk to study the Hippo pathway and have found that Hippo pathway activation can promote cell migration and invasion while Hippo pathway inactivation leads to overgrowth. Thus we propose here that Drosophila can provide a research platform with which to begin addressing how the Hippo pathway can both enhance and suppress tumor progression due to published pro- and anti-tumor functionalities of the Hippo pathway in the same tissue.

  7. Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network

    PubMed Central

    Sun, Shuguo; Irvine, Kenneth D.

    2016-01-01

    The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated, and to define their respective contributions in vivo. PMID:27268910

  8. Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network.

    PubMed

    Sun, Shuguo; Irvine, Kenneth D

    2016-09-01

    The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell-cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated and to define their respective contributions in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Regulation of the Hippo signaling pathway by ubiquitin modification.

    PubMed

    Kim, Youngeun; Jho, Eek-Hoon

    2018-03-01

    The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. β-TrCP is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway. [BMB Reports 2018; 51(3): 143-150].

  10. The Hippo pathway in tissue homeostasis and regeneration.

    PubMed

    Wang, Yu; Yu, Aijuan; Yu, Fa-Xing

    2017-05-01

    While several organs in mammals retain partial regenerative capability following tissue damage, the underlying mechanisms remain unclear. Recently, the Hippo signaling pathway, better known for its function in organ size control, has been shown to play a pivotal role in regulating tissue homeostasis and regeneration. Upon tissue injury, the activity of YAP, the major effector of the Hippo pathway, is transiently induced, which in turn promotes expansion of tissue-resident progenitors and facilitates tissue regeneration. In this review, with a general focus on the Hippo pathway, we will discuss its major components, functions in stem cell biology, involvement in tissue regeneration in different organs, and potential strategies for developing Hippo pathway-targeted regenerative medicines.

  11. The Hippo signaling pathway in liver regeneration and tumorigenesis.

    PubMed

    Hong, Lixin; Cai, Yabo; Jiang, Mingting; Zhou, Dawang; Chen, Lanfen

    2015-01-01

    The Hippo signaling pathway is an evolutionarily conserved signaling module that plays critical roles in liver size control and tumorigenesis. The Hippo pathway consists of a core kinase cascade in which the mammalian Ste20-like kinases (Mst1/2, orthologs of Drosophila Hippo) and their cofactor Salvador (Sav1) form a complex to phosphorylate and activate the large tumor suppressor (Lats1/2). Lats1/2 kinases in turn phosphorylate and inhibit the transcription co-activators, the Yes-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ), two major downstream effectors of the Hippo pathway. Losses of the Hippo pathway components induce aberrant hepatomegaly and tumorigenesis, in which YAP coordinates regulation of cell proliferation and apoptosis and plays an essential role. This review summarizes the current findings of the regulation of Hippo signaling in liver regeneration and tumorigenesis, focusing on how the loss of tumor suppressor components of the Hippo pathway results in liver cancers and discussing the molecular mechanisms that regulate the expression and activation of its downstream effector YAP in liver tumorigenesis. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  12. How Hippo Signaling Pathway Modulates Cardiovascular Development and Diseases.

    PubMed

    Zhou, Wenyi; Zhao, Mingyi

    2018-01-01

    Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway. YAP, the core effecter of the Hippo pathway, may accumulate in the nucleus and initiate transcriptional activity if the pathway is inhibited. The role of Hippo signaling has been widely investigated in organ development and cancers. A heart of normal size and function which is critical for survival could not be generated without the proper regulation of the Hippo tumor suppressor pathway. Recent research has demonstrated a novel role of Hippo signaling in cardiovascular disease in the context of development, hypertrophy, angiogenesis, regeneration, apoptosis, and autophagy. In this review, we summarize the current knowledge of how Hippo signaling modulates pathological processes in cardiovascular disease and discuss potential molecular therapeutic targets.

  13. The Hippo Pathway Targets Rae1 to Regulate Mitosis and Organ Size and to Feed Back to Regulate Upstream Components Merlin, Hippo, and Warts.

    PubMed

    Jahanshahi, Maryam; Hsiao, Kuangfu; Jenny, Andreas; Pfleger, Cathie M

    2016-08-01

    Hippo signaling acts as a master regulatory pathway controlling growth, proliferation, and apoptosis and also ensures that variations in proliferation do not alter organ size. How the pathway coordinates restricting proliferation with organ size control remains a major unanswered question. Here we identify Rae1 as a highly-conserved target of the Hippo Pathway integrating proliferation and organ size. Genetic and biochemical studies in Drosophila cells and tissues and in mammalian cells indicate that Hippo signaling promotes Rae1 degradation downstream of Warts/Lats. In proliferating cells, Rae1 loss restricts cyclin B levels and organ size while Rae1 over-expression increases cyclin B levels and organ size, similar to Hippo Pathway over-activation or loss-of-function, respectively. Importantly, Rae1 regulation by the Hippo Pathway is crucial for its regulation of cyclin B and organ size; reducing Rae1 blocks cyclin B accumulation and suppresses overgrowth caused by Hippo Pathway loss. Surprisingly, in addition to suppressing overgrowth, reducing Rae1 also compromises survival of epithelial tissue overgrowing due to loss of Hippo signaling leading to a tissue "synthetic lethality" phenotype. Excitingly, Rae1 plays a highly conserved role to reduce the levels and activity of the Yki/YAP oncogene. Rae1 increases activation of the core kinases Hippo and Warts and plays a post-transcriptional role to increase the protein levels of the Merlin, Hippo, and Warts components of the pathway; therefore, in addition to Rae1 coordinating organ size regulation with proliferative control, we propose that Rae1 also acts in a feedback circuit to regulate pathway homeostasis.

  14. Hippo pathway - brief overview of its relevance in cancer.

    PubMed

    Zygulska, A L; Krzemieniecki, K; Pierzchalski, P

    2017-06-01

    The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins. The major target of the Hippo core kinases is the mammalian transcriptional activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ). In cancer, the Hippo signalling is inactivated and YAP and TAZ are activated and free to translocate into the nucleus to promote cell proliferation. Nuclear YAP/TAZ activate or suppress transcription factors that regulate target genes involved in cell proliferation, tissue growth, control of organ size and shape or metastasis. The Hippo signalling pathway that controls the most important cellular processes like growth and division appears to be a very promising research subject in the field of cell biology and tissue engineering. It consists of elements that in the cell play the roles of tumour suppressors as well as oncogenes. This 'Janus like' - an opposite activity hidden within one and the same signalling pathway represents a significant obstacle for studying it. This property of the Hippo pathway is worth remembering, as it will appear several times during the discussion of its properties. Here, we will review certain data regarding biology of the Hippo signalling and its interplay with other prominent signalling pathways in the cell, its relevance in cancer development and therapies that might target elements of the Hippo pathway in most human cancers.

  15. Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila.

    PubMed

    Liu, Bo; Zheng, Yonggang; Yin, Feng; Yu, Jianzhong; Silverman, Neal; Pan, Duojia

    2016-01-28

    The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innate immunity whereby Yorkie directly regulates the transcription of the Drosophila IκB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactus mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection by Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo-inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IκB/Cactus transcription in innate immunity, and identify Gram-positive bacteria as extracellular stimuli of Hippo signaling under physiological settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Crosstalk between Hippo signalling and miRNAs in tumour progression.

    PubMed

    Li, Nianshuang; Xie, Chuan; Lu, Nonghua

    2017-04-01

    The Hippo signalling pathway co-ordinately modulates cell regeneration and organ size, and its deregulation contributes to tumorigenesis through many cellular processes, including overproliferation, apoptosis resistance and cell migration. Recent discoveries have shed new light on how microRNAs (miRNAs) are closely linked to the Hippo pathway in tumour progression. Hippo signalling has been reported to affect widespread miRNA biogenesis. In turn, several miRNAs regulate Hippo signalling, which contributes to carcinogenesis. This article will provide an overview of the crosstalk between Hippo signalling and miRNAs in the development of cancer and further appraise potential targets for therapeutic intervention. © 2016 Federation of European Biochemical Societies.

  17. Hippo pathway mediates resistance to cytotoxic drugs.

    PubMed

    Gujral, Taranjit S; Kirschner, Marc W

    2017-05-02

    Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models. Nuclear YAP enhances gemcitabine effectiveness by down-regulating multidrug transporters as well by converting gemcitabine to a less active form, both leading to its increased intracellular availability. Cancer cell lines carrying genetic aberrations that impair the Hippo signaling pathway showed heightened sensitivity to gemcitabine. These findings suggest that "switching off" of the Hippo-YAP pathway could help to prevent or reverse resistance to some cancer therapies.

  18. Tracking hippo in the cancer jungle.

    PubMed

    Suh, Jung H; Saba, Julie D

    2014-07-17

    Signaling through the Hippo pathway controls major aspects of cell growth and proliferation. Focusing on the metabolic consequences of Hippo signaling, Mulvihill and colleagues in this issue of Chemistry & Biology employ a large scale, integrative approach and uncover downstream reorganization of cellular metabolism when the effector TAZ is upregulated, identifying new connections to lipid metabolism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The Hippo Pathway Targets Rae1 to Regulate Mitosis and Organ Size and to Feed Back to Regulate Upstream Components Merlin, Hippo, and Warts

    PubMed Central

    Jenny, Andreas; Pfleger, Cathie M.

    2016-01-01

    Hippo signaling acts as a master regulatory pathway controlling growth, proliferation, and apoptosis and also ensures that variations in proliferation do not alter organ size. How the pathway coordinates restricting proliferation with organ size control remains a major unanswered question. Here we identify Rae1 as a highly-conserved target of the Hippo Pathway integrating proliferation and organ size. Genetic and biochemical studies in Drosophila cells and tissues and in mammalian cells indicate that Hippo signaling promotes Rae1 degradation downstream of Warts/Lats. In proliferating cells, Rae1 loss restricts cyclin B levels and organ size while Rae1 over-expression increases cyclin B levels and organ size, similar to Hippo Pathway over-activation or loss-of-function, respectively. Importantly, Rae1 regulation by the Hippo Pathway is crucial for its regulation of cyclin B and organ size; reducing Rae1 blocks cyclin B accumulation and suppresses overgrowth caused by Hippo Pathway loss. Surprisingly, in addition to suppressing overgrowth, reducing Rae1 also compromises survival of epithelial tissue overgrowing due to loss of Hippo signaling leading to a tissue “synthetic lethality” phenotype. Excitingly, Rae1 plays a highly conserved role to reduce the levels and activity of the Yki/YAP oncogene. Rae1 increases activation of the core kinases Hippo and Warts and plays a post-transcriptional role to increase the protein levels of the Merlin, Hippo, and Warts components of the pathway; therefore, in addition to Rae1 coordinating organ size regulation with proliferative control, we propose that Rae1 also acts in a feedback circuit to regulate pathway homeostasis. PMID:27494403

  20. Hippo-YAP signaling pathway: A new paradigm for cancer therapy.

    PubMed

    Ma, Yanlei; Yang, Yongzhi; Wang, Feng; Wei, Qing; Qin, Huanlong

    2015-11-15

    In the past decades, the Hippo signaling pathway has been delineated and shown to play multiple roles in the control of organ size in both Drosophila and mammals. In mammals, the Hippo pathway is a kinase cascade leading from Mst1/2 to YAP and its paralog TAZ. Several studies have demonstrated that YAP/TAZ is a candidate oncogene and that other members of the Hippo pathway are tumor suppressive genes. The dysregulation of the Hippo pathway has been observed in a variety of cancers. This review chronicles the recent progress in elucidating the function of Hippo signaling in tumorigenesis and provide a rich source of potential targets for cancer therapy. © 2014 UICC.

  1. The Hippo pathway in normal development and cancer.

    PubMed

    Maugeri-Saccà, Marcello; De Maria, Ruggero

    2018-06-01

    The Hippo pathway is a central regulator of organ size and tissue homeostasis. Hippo kinases and adaptor proteins mediate the phosphorylation and inactivation of YAP and TAZ, two closely related transcription co-activators. The Hippo pathway responds to a variety of extracellular and intracellular signals, spanning from cell-cell contact and mechanical cues to ligands of G-protein-coupled receptors and metabolic avenues. In some instances, YAP/TAZ activation is tuned by forces that bypass the Hippo kinase module, adding further complexity to the biology of the pathway. Over the past two decades, the Hippo pathway has increasingly been connected with developmental processes and tissue repair, being intimately tied to the function of tissue-specific progenitor cells. Pervasive activation of YAP/TAZ has been recognized in a multitude of human tumors and connected with the acquisition of malignant traits, including resistance to anticancer therapies, distant dissemination and maintenance of cancer stem cells. On this ground, Hippo-related biomarkers are increasingly investigated in translational studies striving to identify prognostic and predictive factors. In addition, the dependency of many tumors on YAP/TAZ may be exploited for therapeutic purposes. Albeit no direct inhibitors are currently available, drug repositioning approaches provided hints that YAP/TAZ inhibition can be achieved with old drugs, such as cholesterol-lowering agents or compounds blocking bone resorption. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Regulation of the Hippo Pathway Transcription Factor TEAD.

    PubMed

    Lin, Kimberly C; Park, Hyun Woo; Guan, Kun-Liang

    2017-11-01

    The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway. However, recent studies suggest that TEAD itself is actively regulated. Here, we highlight evidence demonstrating Hippo-independent regulation of TEADs and the potential impacts these studies may have on new cancer therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Hippo pathway regulates somatic development and cell proliferation of silkworm.

    PubMed

    Li, Niannian; Tong, Xiaoling; Zeng, Jie; Meng, Gang; Sun, Fuze; Hu, Hai; Song, Jiangbo; Lu, Cheng; Dai, Fangyin

    2018-03-01

    Hippo signaling pathway (signaling pathway Hippo, hereinafter referred to as the Hippo pathway) was the earliest found in Drosophila (Schneck [1]), which can regulate the development of tissues and organs, even some components of the pathway were identified as tumor suppressor [2]. The pathway was more concerned in fruit flies and mice (Schneck [1]), but little attention has been given in silkworm, an important economic and lepidopteran model insect. In this manuscript, we identified major Hippo pathway related genes (Hippo, Salvador, Warts, Mats, Yorkie) in silkworm and named BmHpo, BmSav, BmWts, BmMats, BmYki. The domain organization of these genes was highly conserved in silkworm and other organisms suggesting that they could use similar protein-protein interactions to construct the Hippo kinase cascades. The expression profiles of these genes in silkworm during embryonic, larval, wandering, pupal and adult stages were analyzed, 14 tissues/organs of the day 3, 5th instar larvae (L5D3) as well. Experimental results showed that the expression of Hippo pathway had some influence on the development of silkworm. In order to find out the mechanism of Hippo pathway affecting silkworm development, BmHpo and BmYki were up-regulated and de-regulated in the cell line of Bombyx mori-BmN-SWU1(NS), and the changes of cell proliferation activity and cell cycle were detected. The distribution of BmYki was detected by immunofluorescence technique. This study provides insights into the genes of Hippo pathway which have a certain effect on somatic development and cell proliferation in silkworm. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Roles and regulations of Hippo signaling during preimplantation mouse development.

    PubMed

    Sasaki, Hiroshi

    2017-01-01

    During preimplantation development, mouse embryos form two types of cells, the trophoectoderm (TE) and inner cell mass (ICM), by the early blastocyst stage. This process does not require maternal factors localized in the zygotes, and embryos self-organize at the blastocyst stage through intercellular communications. In terms of the mechanisms of cell fate specification, three historical models have been proposed: the positional model, and the original and newer versions of the polarity model. Recent studies have revealed that the intercellular Hippo signaling pathway plays a central role in the specification of the first cell fates. Hippo signaling is active in the inner cells but inactive in the outer cells. The Hippo-active inner and Hippo-inactive outer cells take the fates of the ICM and the TE, respectively. At the 32-cell stage, E-cadherin-mediated cell-cell adhesion and cell polarization by the Par-aPKC system activates and inactivates the Hippo pathway, respectively. Both mechanisms involve regulation of angiomotin, and cooperation of these mechanisms establishes cell position-dependent activation of Hippo signaling. At the 16-cell stage, however, asymmetric cell division produces the initial differences in Hippo signaling. At this stage, cell polarity is controlled by both Par-aPKC-dependent and -independent mechanisms. All three historical models are explained by the different regulations and roles of Hippo signaling. Based on these findings, I would like to propose the model by which the differences in Hippo signaling among blastomeres is first produced by asymmetric cell division and then enhanced and stabilized by cell position-dependent mechanisms until their fates are fixed. © 2016 Japanese Society of Developmental Biologists.

  5. The Hippo pathway in disease and therapy: cancer and beyond

    PubMed Central

    2014-01-01

    The Hippo tumour suppressor pathway co-ordinates cell proliferation, cell death and cell differentiation to regulate tissue growth control. In mammals, a conserved core Hippo signalling module receives signal inputs on different levels to ensure the proper regulation of YAP/TAZ activities as transcriptional co-activators. While the core module members MST1/2, Salvador, LATS1/2 and MOB1 have been attributed tumour suppressive functions, YAP/TAZ have been mainly described to have oncogenic roles, although some reports provided evidence supporting growth suppressive roles of YAP/TAZ in certain cancer settings. Intriguingly, mammalian Hippo signalling is also implicated in non-cancer diseases and plays a role in tissue regeneration following injury. Cumulatively, these findings indicate that the pharmacological inhibition or activation of the Hippo pathway could be desirable depending on the disease context. In this review, we first summarise the functions of the mammalian Hippo pathway in tumour formation, and then discuss non-cancer diseases involving Hippo signalling core components with a specific focus on our current understanding of the non-cancer roles of MST1/2 and YAP/TAZ. In addition, the pros and cons of possible pharmacological interventions with Hippo signalling will be reviewed, with particular emphasis on anti-cancer drug development and regenerative medicine. PMID:25097725

  6. Hippo circuitry and the redox modulation of hippo components in cancer cell fate decisions.

    PubMed

    Ashraf, Asma; Pervaiz, Shazib

    2015-12-01

    Meticulous and precise control of organ size is undoubtedly one of the most pivotal processes in mammalian development and regeneration along with cell differentiation, morphogenesis and programmed cell death. These processes are strictly regulated by complex and highly coordinated mechanisms to maintain a steady growth state. There are a number of extrinsic and intrinsic factors that dictate the total number and/or size of cells by influencing growth, proliferation, differentiation and cell death. Multiple pathways, such as those involved in promoting organ size and others that restrict disproportionate tissue growth act simultaneously to maintain cellular and tissue homeostasis. Aberrations at any level in these organ size-regulating processes can lead to various pathological states with cancers being the most formidable one (Yin and Zhang, 2011). Extensive research in the realm of growth control has led to the identification of the Hippo-signaling pathway as a critical network in modulating tissue growth via its effect on multiple signaling pathways and through intricate crosstalk with proteins that regulate cell polarity, adhesion and cell-cell interactions (Zhao et al., 2011b). The Hippo pathway controls cell number and organ size by transducing signals from the plasma membrane to the nucleus to regulate the expression of genes involved in cell fate determination (Shi et al., 2015). In this review, we summarize the recent discoveries concerning Hippo pathway, its diversiform regulation in mammals as well as its implications in cancers, and highlight the possible role of oxidative stress in Hippo pathway regulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas

    PubMed Central

    Deel, Michael D.; Li, Jenny J.; Crose, Lisa E. S.; Linardic, Corinne M.

    2015-01-01

    The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as co-activators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas. PMID:26389076

  8. A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas.

    PubMed

    Deel, Michael D; Li, Jenny J; Crose, Lisa E S; Linardic, Corinne M

    2015-01-01

    The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as co-activators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas.

  9. Hippo Pathway: An Emerging Regulator of Craniofacial and Dental Development.

    PubMed

    Wang, J; Martin, J F

    2017-10-01

    The evolutionarily conserved Hippo signaling pathway is a vital regulator of organ size that fine-tunes cell proliferation, apoptosis, and differentiation. A number of important studies have revealed critical roles of Hippo signaling and its effectors Yap (Yes-associated protein) and Taz (transcriptional coactivator with PDZ binding motif) in tissue development, homeostasis, and regeneration, as well as in tumorigenesis. In addition, recent studies have shown evidence of crosstalk between the Hippo pathway and other key signaling pathways, such as Wnt signaling, that not only regulates developmental processes but also contributes to disease pathogenesis. In this review, we summarize the major discoveries in the field of Hippo signaling and what has been learned about its regulation and crosstalk with other signaling pathways, with a particular focus on recent findings involving the Hippo-Yap pathway in craniofacial and tooth development. New and exciting studies of the Hippo pathway are anticipated that will significantly improve our understanding of the molecular mechanisms of human craniofacial and tooth development and disease and will ultimately lead to the development of new therapies.

  10. Salvador has an extended SARAH domain that mediates binding to Hippo kinase.

    PubMed

    Cairns, Leah; Tran, Thao; Fowl, Brendan H; Patterson, Angela; Kim, Yoo Jin; Bothner, Brian; Kavran, Jennifer M

    2018-04-13

    The Hippo pathway controls cell proliferation and differentiation through the precisely tuned activity of a core kinase cassette. The activity of Hippo kinase is modulated by interactions between its C-terminal coiled-coil, termed the SARAH domain, and the SARAH domains of either dRassF or Salvador. Here, we wanted to understand the molecular basis of SARAH domain-mediated interactions and their influence on Hippo kinase activity. We focused on Salvador, a positive effector of Hippo activity and the least well-characterized SARAH domain-containing protein. We determined the crystal structure of a complex between Salvador and Hippo SARAH domains from Drosophila This structure provided insight into the organization of the Salvador SARAH domain including a folded N-terminal extension that expands the binding interface with Hippo SARAH domain. We also found that this extension improves the solubility of the Salvador SARAH domain, enhances binding to Hippo, and is unique to Salvador. We therefore suggest expanding the definition of the Salvador SARAH domain to include this extended region. The heterodimeric assembly observed in the crystal was confirmed by cross-linked MS and provided a structural basis for the mutually exclusive interactions of Hippo with either dRassF or Salvador. Of note, Salvador influenced the kinase activity of Mst2, the mammalian Hippo homolog. In co-transfected HEK293T cells, human Salvador increased the levels of Mst2 autophosphorylation and Mst2-mediated phosphorylation of select substrates, whereas Salvador SARAH domain inhibited Mst2 autophosphorylation in vitro These results suggest Salvador enhances the effects of Hippo kinase activity at multiple points in the Hippo pathway. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. 50 CFR 665.401 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Lehi/maroobw red snapper, silvermouth Aphareus rutilans. Gogunafon/aiwe gray snapper, jobfish Aprion virescens. Tarakitu/etam Giant trevally, jack Caranx ignobilis. Tarakiton attelong/orong Black trevally... grouper Variola louti. Buninas agaga'/falaghal moroobw red snapper Etelis carbunculus. Abuninas...

  12. 50 CFR 665.401 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Lehi/maroobw red snapper, silvermouth Aphareus rutilans. Gogunafon/aiwe gray snapper, jobfish Aprion virescens. Tarakitu/etam Giant trevally, jack Caranx ignobilis. Tarakiton attelong/orong Black trevally... grouper Variola louti. Buninas agaga'/falaghal moroobw red snapper Etelis carbunculus. Abuninas...

  13. 50 CFR 665.401 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Lehi/maroobw red snapper, silvermouth Aphareus rutilans. Gogunafon/aiwe gray snapper, jobfish Aprion virescens. Tarakitu/etam Giant trevally, jack Caranx ignobilis. Tarakiton attelong/orong Black trevally... grouper Variola louti. Buninas agaga'/falaghal moroobw red snapper Etelis carbunculus. Abuninas...

  14. Emerging roles of Hippo signaling in inflammation and YAP-driven tumor immunity.

    PubMed

    Zhou, Yuhang; Huang, Tingting; Zhang, Jinglin; Cheng, Alfred S L; Yu, Jun; Kang, Wei; To, Ka Fai

    2018-07-10

    Initially identified as a cell and organ size controller, Hippo pathway turns into a hotspot for researchers. Within recent years, more and more mechanisms about Hippo pathway were uncovered. Even though Hippo signaling has been revealed to exert controversial roles according to different cell context and microenvironment, which is because of its diversified interplays with a great variety of signaling transduction cascades; mechanisms other than size-limitation, however, remain to be elucidated. Recently, a growing number of studies tend to put Hippo on inflammatory and immunological focus: its antimicrobial role in flies, its pro- or anti-inflammation in mammals, as well as its relevance to cancerous immunity. From inflammation to tumor immunogenicity, Hippo has been gradually justified to play a crucial role. This review summarized the latest findings regarding the involvement of Hippo pathway in immunity, and a more comprehensive understanding of Hippo pathway will shed light on clinical translational potential even precision medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans.

    PubMed

    Feng, Guoxin; Zhu, Zhiwen; Li, Wen-Jun; Lin, Qirong; Chai, Yongping; Dong, Meng-Qiu; Ou, Guangshuo

    2017-02-01

    Precise positioning of cells is crucial for metazoan development. Despite immense progress in the elucidation of the attractive cues of cell migration, the repulsive mechanisms that prevent the formation of secondary leading edges remain less investigated. Here, we demonstrate that Caenorhabditis elegans Hippo kinases promote cell migration along the anterior-posterior body axis via the inhibition of dorsal-ventral (DV) migration. Ectopic DV polarization was also demonstrated in gain-of-function mutant animals for C. elegans RhoG MIG-2. We identified serine 139 of MIG-2 as a novel conserved Hippo kinase phosphorylation site and demonstrated that purified Hippo kinases directly phosphorylate MIG-2 S139 Live imaging analysis of genome-edited animals indicates that MIG-2 S139 phosphorylation impedes actin assembly in migrating cells. Intriguingly, Hippo kinases are excluded from the leading edge in wild-type cells, while MIG-2 loss induces uniform distribution of Hippo kinases. We provide evidence that Hippo kinases inhibit RhoG activity locally and are in turn restricted to the cell body by RhoG-mediated polarization. Therefore, we propose that the Hippo-RhoG feedback regulation maintains cell polarity during directional cell motility. © 2016 The Authors.

  16. The history and regulatory mechanism of the Hippo pathway

    PubMed Central

    Kim, Wantae; Jho, Eek-hoon

    2018-01-01

    How the organ size is adjusted to the proper size during development and how organs know that they reach the original size during regeneration remain long-standing questions. Based on studies using multiple model organisms and approaches for over 20 years, a consensus has been established that the Hippo pathway plays crucial roles in controlling organ size and maintaining tissue homeostasis. Given the significance of these processes, the dysregulation of the Hippo pathway has also implicated various diseases, such as tissue degeneration and cancer. By regulating the downstream transcriptional coactivators YAP and TAZ, the Hippo pathway coordinates cell proliferation and apoptosis in response to a variety of signals including cell contact inhibition, polarity, mechanical sensation and soluble factors. Since the core components and their functions of the Hippo pathway are evolutionarily conserved, this pathway serves as a global regulator of organ size control. Therefore, further investigation of the regulatory mechanisms will provide physiological insights to better understand tissue homeostasis. In this review, the historical developments and current understandings of the regulatory mechanism of Hippo signaling pathway are discussed. PMID:29397869

  17. Hippo signaling controls cell cycle and restricts cell plasticity in planarians

    PubMed Central

    de Sousa, Nídia; Rodríguez-Esteban, Gustavo; Rojo-Laguna, Jose Ignacio; Saló, Emili

    2018-01-01

    The Hippo pathway plays a key role in regulating cell turnover in adult tissues, and abnormalities in this pathway are consistently associated with human cancers. Hippo was initially implicated in the control of cell proliferation and death, and its inhibition is linked to the expansion of stem cells and progenitors, leading to larger organ size and tumor formation. To understand the mechanism by which Hippo directs cell renewal and promotes stemness, we studied its function in planarians. These stem cell–based organisms are ideal models for the analysis of the complex cellular events underlying tissue renewal in the whole organism. hippo RNA interference (RNAi) in planarians decreased apoptotic cell death, induced cell cycle arrest, and could promote the dedifferentiation of postmitotic cells. hippo RNAi resulted in extensive undifferentiated areas and overgrowths, with no effect on body size or cell number. We propose an essential role for hippo in controlling cell cycle, restricting cell plasticity, and thereby preventing tumoral transformation. PMID:29357350

  18. The Roles of NDR Protein Kinases in Hippo Signalling.

    PubMed

    Hergovich, Alexander

    2016-05-18

    The Hippo tumour suppressor pathway has emerged as a critical regulator of tissue growth through controlling cellular processes such as cell proliferation, death, differentiation and stemness. Traditionally, the core cassette of the Hippo pathway includes the MST1/2 protein kinases, the LATS1/2 protein kinases, and the MOB1 scaffold signal transducer, which together regulate the transcriptional co-activator functions of the proto-oncoproteins YAP and TAZ through LATS1/2-mediated phosphorylation of YAP/TAZ. Recent research has identified additional kinases, such as NDR1/2 (also known as STK38/STK38L) and MAP4Ks, which should be considered as novel members of the Hippo core cassette. While these efforts helped to expand our understanding of Hippo core signalling, they also began to provide insights into the complexity and redundancy of the Hippo signalling network. Here, we focus on summarising our current knowledge of the regulation and functions of mammalian NDR kinases, discussing parallels between the NDR pathways in Drosophila and mammals. Initially, we provide a general overview of the cellular functions of NDR kinases in cell cycle progression, centrosome biology, apoptosis, autophagy, DNA damage signalling, immunology and neurobiology. Finally, we put particular emphasis on discussing NDR1/2 as YAP kinases downstream of MST1/2 and MOB1 signalling in Hippo signalling.

  19. The Hippo-YAP signaling pathway and contact inhibition of growth

    PubMed Central

    Gumbiner, Barry M.; Kim, Nam-Gyun

    2014-01-01

    ABSTRACT The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin–catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes. PMID:24532814

  20. Ubiquitin-Dependent Regulation of the Mammalian Hippo Pathway: Therapeutic Implications for Cancer

    PubMed Central

    Nguyen, Thanh Hung

    2018-01-01

    The Hippo pathway serves as a key barrier for oncogenic transformation. It acts by limiting the activity of the proto-oncogenes YAP and TAZ. Reduced Hippo signaling and elevated YAP/TAZ activities are frequently observed in various types of tumors. Emerging evidence suggests that the ubiquitin system plays an important role in regulating Hippo pathway activity. Deregulation of ubiquitin ligases and of deubiquitinating enzymes has been implicated in increased YAP/TAZ activity in cancer. In this article, we review recent insights into the ubiquitin-mediated regulation of the mammalian Hippo pathway, its deregulation in cancer, and possibilities for targeting the Hippo pathway through the ubiquitin system. PMID:29673168

  1. Ubiquitin-Dependent Regulation of the Mammalian Hippo Pathway: Therapeutic Implications for Cancer.

    PubMed

    Nguyen, Thanh Hung; Kugler, Jan-Michael

    2018-04-17

    The Hippo pathway serves as a key barrier for oncogenic transformation. It acts by limiting the activity of the proto-oncogenes YAP and TAZ. Reduced Hippo signaling and elevated YAP/TAZ activities are frequently observed in various types of tumors. Emerging evidence suggests that the ubiquitin system plays an important role in regulating Hippo pathway activity. Deregulation of ubiquitin ligases and of deubiquitinating enzymes has been implicated in increased YAP/TAZ activity in cancer. In this article, we review recent insights into the ubiquitin-mediated regulation of the mammalian Hippo pathway, its deregulation in cancer, and possibilities for targeting the Hippo pathway through the ubiquitin system.

  2. Hippo Signaling in Mitosis: An Updated View in Light of the MEN Pathway.

    PubMed

    Hergovich, Alexander

    2017-01-01

    The Hippo pathway is an essential tumor suppressor signaling network that coordinates cell proliferation, death, and differentiation in higher eukaryotes. Intriguingly, the core components of the Hippo pathway are conserved from yeast to man, with the yeast analogs of mammalian MST1/2 (fly Hippo), MOB1 (fly Mats), LATS1/2 (fly Warts), and NDR1/2 (fly Tricornered) functioning as essential components of the mitotic exit network (MEN). Here, we update our previous summary of mitotic functions of Hippo core components in Drosophila melanogaster and mammals, with particular emphasis on similarities between the yeast MEN pathway and mitotic Hippo signaling. Mitotic functions of YAP and TAZ, the two main effectors of Hippo signaling, are also discussed.

  3. The Hippo signaling pathway in stem cell biology and cancer

    PubMed Central

    Mo, Jung-Soon; Park, Hyun Woo; Guan, Kun-Liang

    2014-01-01

    The Hippo signaling pathway, consisting of a highly conserved kinase cascade (MST and Lats) and downstream transcription coactivators (YAP and TAZ), plays a key role in tissue homeostasis and organ size control by regulating tissue-specific stem cells. Moreover, this pathway plays a prominent role in tissue repair and regeneration. Dysregulation of the Hippo pathway is associated with cancer development. Recent studies have revealed a complex network of upstream inputs, including cell density, mechanical sensation, and G-protein-coupled receptor (GPCR) signaling, that modulate Hippo pathway activity. This review focuses on the role of the Hippo pathway in stem cell biology and its potential implications in tissue homeostasis and cancer. PMID:24825474

  4. The Spectrin cytoskeleton regulates the Hippo signalling pathway.

    PubMed

    Fletcher, Georgina C; Elbediwy, Ahmed; Khanal, Ichha; Ribeiro, Paulo S; Tapon, Nic; Thompson, Barry J

    2015-04-01

    The Spectrin cytoskeleton is known to be polarised in epithelial cells, yet its role remains poorly understood. Here, we show that the Spectrin cytoskeleton controls Hippo signalling. In the developing Drosophila wing and eye, loss of apical Spectrins (alpha/beta-heavy dimers) produces tissue overgrowth and mis-regulation of Hippo target genes, similar to loss of Crumbs (Crb) or the FERM-domain protein Expanded (Ex). Apical beta-heavy Spectrin binds to Ex and co-localises with it at the apical membrane to antagonise Yki activity. Interestingly, in both the ovarian follicular epithelium and intestinal epithelium of Drosophila, apical Spectrins and Crb are dispensable for repression of Yki, while basolateral Spectrins (alpha/beta dimers) are essential. Finally, the Spectrin cytoskeleton is required to regulate the localisation of the Hippo pathway effector YAP in response to cell density human epithelial cells. Our findings identify both apical and basolateral Spectrins as regulators of Hippo signalling and suggest Spectrins as potential mechanosensors. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  5. The Hippo signal transduction network for exercise physiologists

    PubMed Central

    Hamilton, D. Lee; Tremblay, Annie M.

    2016-01-01

    The ubiquitous transcriptional coactivators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by coactivating the Tead transcription factors. Being at the center of the Hippo signaling network, Yap and Taz are regulated by the Hippo kinase cassette and additionally by a plethora of exercise-associated signals and signaling modules. These include mechanotransduction, the AKT-mTORC1 network, the SMAD transcription factors, hypoxia, glucose homeostasis, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and IL-6. Consequently, exercise should alter Hippo signaling in several organs to mediate at least some aspects of the organ-specific adaptations to exercise. Indeed, Tead1 overexpression in muscle fibers has been shown to promote a fast-to-slow fiber type switch, whereas Yap in muscle fibers and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte adaptations, respectively. Finally, genome-wide association studies in humans have linked the Hippo pathway members LATS2, TEAD1, YAP1, VGLL2, VGLL3, and VGLL4 to body height, which is a key factor in sports. PMID:26940657

  6. The Hippo signaling pathway provides novel anti-cancer drug targets

    PubMed Central

    Bae, June Sung; Kim, Sun Mi; Lee, Ho

    2017-01-01

    The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development. Many biological elements, including mechanical strain on the cell, cell polarity/adhesion molecules, other signaling pathways (e.g., G-protein-coupled receptor, epidermal growth factor receptor, Wnt, Notch, and transforming growth factor β/bone morphogenic protein), and cellular metabolic status, can promote oncogenesis through synergistic association with components of the Hippo signaling pathway. Here, we review the signaling networks that interact with the Hippo signaling pathway and discuss the potential of using drugs that inhibit YAP and TAZ activity for cancer therapy. PMID:28035075

  7. The Hippo signaling pathway provides novel anti-cancer drug targets.

    PubMed

    Bae, June Sung; Kim, Sun Mi; Lee, Ho

    2017-02-28

    The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development. Many biological elements, including mechanical strain on the cell, cell polarity/adhesion molecules, other signaling pathways (e.g., G-protein-coupled receptor, epidermal growth factor receptor, Wnt, Notch, and transforming growth factor β/bone morphogenic protein), and cellular metabolic status, can promote oncogenesis through synergistic association with components of the Hippo signaling pathway. Here, we review the signaling networks that interact with the Hippo signaling pathway and discuss the potential of using drugs that inhibit YAP and TAZ activity for cancer therapy.

  8. 20. MANUAL JACKING STATION UNIT 23 GORGE POWERHOUSE. JACKING FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. MANUAL JACKING STATION UNIT 23 GORGE POWERHOUSE. JACKING FOR UNITS 23, 22, AND 21 HAS BEEN AUTOMATED FOR MANY YEARS BUT THE MANUAL JACKING STATIONS REMAIN IN PLACE AND FUNCTIONAL, 1989. - Skagit Power Development, Gorge Powerhouse, On Skagit River, 0.4 mile upstream from Newhalem, Newhalem, Whatcom County, WA

  9. Targeting the Hippo Signaling Pathway for Tissue Regeneration and Cancer Therapy.

    PubMed

    Juan, Wen Chun; Hong, Wanjin

    2016-08-30

    The Hippo signaling pathway is a highly-conserved developmental pathway that plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. The YES-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ) are two important transcriptional co-activators that are negatively regulated by the Hippo signaling pathway. By binding to transcription factors, especially the TEA domain transcription factors (TEADs), YAP and TAZ induce the expression of growth-promoting genes, which can promote organ regeneration after injury. Therefore, controlled activation of YAP and TAZ can be useful for regenerative medicine. However, aberrant activation of YAP and TAZ due to deregulation of the Hippo pathway or overexpression of YAP/TAZ and TEADs can promote cancer development. Hence, pharmacological inhibition of YAP and TAZ may be a useful approach to treat tumors with high YAP and/or TAZ activity. In this review, we present the mechanisms regulating the Hippo pathway, the role of the Hippo pathway in tissue repair and cancer, as well as a detailed analysis of the different strategies to target the Hippo signaling pathway and the genes regulated by YAP and TAZ for regenerative medicine and cancer therapy.

  10. Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism.

    PubMed

    Ardestani, Amin; Lupse, Blaz; Maedler, Kathrin

    2018-05-05

    The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer. In this review we summarize the connection between key Hippo components and metabolism, and how this interplay regulates cellular metabolism and metabolic pathways. The emerging function of Hippo in the regulation of metabolic homeostasis under physiological and pathological conditions is highlighted. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. USP21 regulates Hippo pathway activity by mediating MARK protein turnover.

    PubMed

    Nguyen, Hung Thanh; Kugler, Jan-Michael; Loya, Anand C; Cohen, Stephen M

    2017-09-08

    The Hippo pathway, which acts to repress the activity of YAP and TAZ trancriptional co-activators, serve as a barrier for oncogenic transformation. Unlike other oncoproteins, YAP and TAZ are rarely activated by mutations or amplified in cancer. However, elevated YAP/TAZ activity is frequently observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components and deubiquitylating enzymes that counteract these ubiquitin ligases have been implicated in human cancer. Here we identify the USP21 deubiquitylating enzyme as a novel regulator of Hippo pathway activity. We provide evidence that USP21 regulates YAP/TAZ activity by controlling the stability of MARK kinases, which promote Hippo signaling. Low expression of USP21 in early stage renal clear cell carcinoma suggests that USP21 may be a useful biomarker.

  12. Emerging role of Hippo pathway in gastric and other gastrointestinal cancers.

    PubMed

    Kang, Wei; Cheng, Alfred S L; Yu, Jun; To, Ka Fai

    2016-01-21

    More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1 (YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZ-binding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and microRNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.

  13. Hippo Experiment Data Access and Subseting System

    NASA Astrophysics Data System (ADS)

    Krassovski, M.; Hook, L.; Boden, T.

    2014-12-01

    HIAPER Pole-to-Pole Observations (HIPPO) was an NSF- and NOAA-funded, multi-year global airborne research project to survey the latitudinal and vertical distribution of greenhouse and related gases, and aerosols. Project scientists and support staff flew five month-long missions over the Pacific Basin on the NSF/NCAR Gulfstream V, High-performance Instrumented Airborne Platform for Environmental Research (HIAPER) aircraft between January 2009 and September 2011, spread throughout the annual cycle, from the surface to 14 km in altitude, and from 87°N to 67°S. Data from the HIPPO study of greenhouse gases and aerosols are now available to the atmospheric research community and the public. This comprehensive dataset provides the first high-resolution vertically resolved measurements of over 90 unique atmospheric species from nearly pole-to-pole over the Pacific Ocean across all seasons. The suite of atmospheric trace gases and aerosols is pertinent to understanding the carbon cycle and challenging global climate models. This dataset will provide opportunities for research across a broad spectrum of Earth sciences, including those analyzing the evolution in time and space of the greenhouse gases that affect global climate. The Carbon Dioxide Information Analysis Center (CDIAC) at Oak Ridge National Laboratory (ORNL) provides data management support for the HIPPO experiment including long-term data storage and dissemination. CDIAC has developed a relational database to house HIPPO merged 10-second meteorology, atmospheric chemistry, and aerosol data. This data set provides measurements from all Missions, 1 through 5, that took place from January of 2009 to September 2011. This presentation introduces newly build database and web interface, reflects the present state and functionality of the HIPPO Database and Exploration System as well as future plans for expansion and inclusion of combined discrete flask and GC sample GHG, Halocarbon, and hydrocarbon data.

  14. Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST): A Pilot Randomized Trial.

    PubMed

    Kosa, S Daisy; Gafni, Amiram; House, Andrew A; Lawrence, JulieAnn; Moist, Louise; Nathoo, Bharat; Tam, Paul; Sarabia, Alicia; Thabane, Lehana; Wu, George; Lok, Charmaine E

    2017-03-01

    We developed the Hemodialysis Infection Prevention Protocols Ontario-Shower Technique (HIPPO-ST) to permit hemodialysis (HD) patients with central venous catheters (catheters) to shower without additional infection risk. Our primary objective was to determine the feasibility of conducting a parallel randomized controlled trial (RCT) to evaluate the impact of HIPPO-ST on catheter-related bacteremia (CRB) in adult HD patients. Adult HD patients using catheters were recruited from 11 HD units. Patients were randomized to receive HIPPO-ST or standard care and were followed up for 6 months. Only CRB-outcome assessors were blinded. For the study to be considered feasible, 4 of 5 feasibility outcomes, each with its own statistical threshold for success, must have been achieved. A total of 68 patients were randomized (33 HIPPO-ST and 35 control) and were followed up to 6 months. Of 5 measures of feasibility, 4 were achieved: (1) accurate CRB rate documented (threshold: κ level >0.80); (2) 97.8% (279/285) of satellite HD patients with catheters were screened (threshold: >95%); (3) 88% (23/26) in the HIPPO-ST arm were successfully educated by 6 months (threshold: >80%); and (4) 0% (0/29) patients in the control arm were "contaminated," that is, using HIPPO-ST (threshold: <5%). However, only 44.2% (72/163) of eligible patients consented to participate (threshold: >80%). The rate of CRB was similarly low in HIPPO-ST and control groups (0.68 vs. 0.88/1000 catheter days). This HIPPO-ST pilot study demonstrated the feasibility of the larger HIPPO-ST study, especially given the high levels of education success with the HIPPO-ST arm and the low levels of contamination in the control arm.

  15. First time isolation of Photobacterium damselae subsp. damselae from Caranx sexfasciatus in Persian Gulf, Iran

    PubMed Central

    Hassanzadeh, Yashgin; Bahador, Nima; Baseri-Salehi, Majid

    2015-01-01

    Background and Objective: Photobacterium damselae subsp. damselae is a marine pathogenic bacterium which causes disease in marine animals and human. This bacterium mostly found in coastal shallow seawater. So, the aim of this study was isolation and characterization of Photobacterium damselae subsp. damselae from edible fish of Persian Gulf, Bandar Abbas. Material and Methods: Totally 100 fish from different species were evaluated and out of that 5 different types of fish with external symptoms including: Caranx sexfasciatus, Lethrinus olivaceus, Scomberoid tol, Auxis thazard and Liza macrolepis, were collected from Bandar Abbas local fish market in September 2013. The samples were cultured on Marin Agar 2216 and Thiosulfate Citrate Bile salts Sucrose Agar media and incubated at 25°C for 48 hrs. Then the isolates were characterized using biochemical (API 20 NE system) and molecular techniques. In addition, antibiotic susceptibility, presence of poly β hydroxy butyrate and hemolysis activity of isolates were evaluated. Results and Conclusion: Entirely, 30 Gram negative bacterial colonies were isolated from the selected fish. Among the isolates, two suspected colonies were identified as Photobacterium damselae from Caranx sexfasciatus with API 20NE biochemical test. This results confirmed by 16s rRNA sequencing method. Both isolates showed α hemolytic with existence of β hydroxyl butyrate. Furthermore, the isolates were susceptible to ciprofloxacin, chloramphenicol and nalidixic acid. Conclusion: Overall, the study indicated first time isolation of this bacterium from one type of fish caught from Persian Gulf, which warns us to pay more attention to fishery in this geographical area. PMID:26668707

  16. Targeting the Hippo Signaling Pathway for Tissue Regeneration and Cancer Therapy

    PubMed Central

    Juan, Wen Chun; Hong, Wanjin

    2016-01-01

    The Hippo signaling pathway is a highly-conserved developmental pathway that plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. The YES-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ) are two important transcriptional co-activators that are negatively regulated by the Hippo signaling pathway. By binding to transcription factors, especially the TEA domain transcription factors (TEADs), YAP and TAZ induce the expression of growth-promoting genes, which can promote organ regeneration after injury. Therefore, controlled activation of YAP and TAZ can be useful for regenerative medicine. However, aberrant activation of YAP and TAZ due to deregulation of the Hippo pathway or overexpression of YAP/TAZ and TEADs can promote cancer development. Hence, pharmacological inhibition of YAP and TAZ may be a useful approach to treat tumors with high YAP and/or TAZ activity. In this review, we present the mechanisms regulating the Hippo pathway, the role of the Hippo pathway in tissue repair and cancer, as well as a detailed analysis of the different strategies to target the Hippo signaling pathway and the genes regulated by YAP and TAZ for regenerative medicine and cancer therapy. PMID:27589805

  17. Kibra and Merlin Activate the Hippo Pathway Spatially Distinct from and Independent of Expanded.

    PubMed

    Su, Ting; Ludwig, Michael Z; Xu, Jiajie; Fehon, Richard G

    2017-03-13

    The Hippo pathway is emerging as a key evolutionarily conserved signaling mechanism that controls organ size. Three membrane-associated proteins, Kibra, Merlin, and Expanded, regulate pathway activity, but the precise molecular mechanism by which they function is still poorly understood. Here we provide evidence that Merlin and Kibra activate Hippo signaling in parallel to Expanded at a spatially distinct cellular domain, the medial apical cortex. Merlin and Kibra together recruit the adapter protein Salvador, which in turn recruits the core kinase Hippo. In addition, we show that Crumbs has a dual effect on Hippo signaling. Crumbs promotes the ability of Expanded to activate the pathway but also sequesters Kibra to downregulate Hippo signaling. Together, our findings elucidate the mechanism of Hippo pathway activation by Merlin and Kibra, identify a subcellular domain for Hippo pathway regulation, and demonstrate differential activity of upstream regulators in different subcellular domains. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation.

    PubMed

    Ahmed, Abdulrzag F; de Bock, Charles E; Lincz, Lisa F; Pundavela, Jay; Zouikr, Ihssane; Sontag, Estelle; Hondermarck, Hubert; Thorne, Rick F

    2015-12-01

    The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.

  19. The role of the Hippo pathway in human disease and tumorigenesis

    PubMed Central

    2014-01-01

    Understanding the molecular nature of human cancer is essential to the development of effective and personalized therapies. Several different molecular signal transduction pathways drive tumorigenesis when deregulated and respond to different types of therapeutic interventions. The Hippo signaling pathway has been demonstrated to play a central role in the regulation of tissue and organ size during development. The deregulation of Hippo signaling leads to a concurrent combination of uncontrolled cellular proliferation and inhibition of apoptosis, two key hallmarks in cancer development. The molecular nature of this pathway was first uncovered in Drosophila melanogaster through genetic screens to identify regulators of cell growth and cell division. The pathway is strongly conserved in humans, rendering Drosophila a suitable and efficient model system to better understand the molecular nature of this pathway. In the present study, we review the current understanding of the molecular mechanism and clinical impact of the Hippo pathway. Current studies have demonstrated that a variety of deregulated molecules can alter Hippo signaling, leading to the constitutive activation of the transcriptional activator YAP or its paralog TAZ. Additionally, the Hippo pathway integrates inputs from a number of growth signaling pathways, positioning the Hippo pathway in a central role in the regulation of tissue size. Importantly, deregulated Hippo signaling is frequently observed in human cancers. YAP is commonly activated in a number of in vitro and in vivo models of tumorigenesis, as well as a number of human cancers. The common activation of YAP in many different tumor types provides an attractive target for potential therapeutic intervention. PMID:25097728

  20. Hippo Cascade Controls Lineage Commitment of Liver Tumors in Mice and Humans.

    PubMed

    Zhang, Shanshan; Wang, Jingxiao; Wang, Haichuan; Fan, Lingling; Fan, Biao; Zeng, Billy; Tao, Junyan; Li, Xiaolei; Che, Li; Cigliano, Antonio; Ribback, Silvia; Dombrowski, Frank; Chen, Bin; Cong, Wenming; Wei, Lixin; Calvisi, Diego F; Chen, Xin

    2018-04-01

    Primary liver cancer consists mainly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). A subset of human HCCs expresses a ICC-like gene signature and is classified as ICC-like HCC. The Hippo pathway is a critical regulator of normal and malignant liver development. However, the precise function(s) of the Hippo cascade along liver carcinogenesis remain to be fully delineated. The role of the Hippo pathway in a murine mixed HCC/ICC model induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated. The authors demonstrated the inactivation of Hippo in AKT/Ras liver tumors leading to nuclear localization of Yap and TAZ. Coexpression of AKT/Ras with Lats2, which activates Hippo, or the dominant negative form of TEAD2 (dnTEAD2), which blocks Yap/TAZ activity, resulted in delayed hepatocarcinogenesis and elimination of ICC-like lesions in the liver. Mechanistically, Notch2 expression was found to be down-regulated by the Hippo pathway in liver tumors. Overexpression of Lats2 or dnTEAD2 in human HCC cell lines inhibited their growth and led to the decreased expression of ICC-like markers, as well as Notch2 expression. Altogether, this study supports the key role of the Hippo cascade in regulating the differentiation status of liver tumors. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. Analysis of Hippo and TGFβ signaling in polarizing epithelial cells and mouse embryos.

    PubMed

    Narimatsu, Masahiro; Labibi, Batool; Wrana, Jeffrey L; Attisano, Liliana

    2016-01-01

    The Hippo signaling pathway is involved in numerous biological events ranging from early development to organogenesis and when disrupted, impacts various human diseases including cancer. The Hippo pathway also interacts with and controls the activity of other signaling pathways such as the TGFβ/Smad pathway, in which Hippo pathway activity influences the subcellular localization of Smad transcription factors. Here, we describe techniques for examining crosstalk between Hippo and TGFβ signaling in polarizing mammary epithelial cells. In addition, we provide detailed methods for analyzing the subcellular localization of the Hippo pathway effectors, Taz and Yap using both in vitro cultured epithelial cells and in vivo in pregastrulation mouse embryos. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  2. EPICS Controlled Collimator for Controlling Beam Sizes in HIPPO

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Napolitano, Arthur Soriano; Vogel, Sven C.

    2017-08-03

    Controlling the beam spot size and shape in a diffraction experiment determines the probed sample volume. The HIPPO - High-Pressure-Preferred Orientation– neutron time-offlight diffractometer is located at the Lujan Neutron Scattering Center in Los Alamos National Laboratories. HIPPO characterizes microstructural parameters, such as phase composition, strains, grain size, or texture, of bulk (cm-sized) samples. In the current setup, the beam spot has a 10 mm diameter. Using a collimator, consisting of two pairs of neutron absorbing boron-nitride slabs, horizontal and vertical dimensions of a rectangular beam spot can be defined. Using the HIPPO robotic sample changer for sample motion, themore » collimator would enable scanning of e.g. cylindrical samples along the cylinder axis by probing slices of such samples. The project presented here describes implementation of such a collimator, in particular the motion control software. We utilized the EPICS (Experimental Physics Interface and Control System) software interface to integrate the collimator control into the HIPPO instrument control system. Using EPICS, commands are sent to commercial stepper motors that move the beam windows.« less

  3. Defining the Protein–Protein Interaction Network of the Human Hippo Pathway*

    PubMed Central

    Wang, Wenqi; Li, Xu; Huang, Jun; Feng, Lin; Dolinta, Keithlee G.; Chen, Junjie

    2014-01-01

    The Hippo pathway, which is conserved from Drosophila to mammals, has been recognized as a tumor suppressor signaling pathway governing cell proliferation and apoptosis, two key events involved in organ size control and tumorigenesis. Although several upstream regulators, the conserved kinase cascade and key downstream effectors including nuclear transcriptional factors have been defined, the global organization of this signaling pathway is not been fully understood. Thus, we conducted a proteomic analysis of human Hippo pathway, which revealed the involvement of an extensive protein–protein interaction network in this pathway. The mass spectrometry data were deposited to ProteomeXchange with identifier PXD000415. Our data suggest that 550 interactions within 343 unique protein components constitute the central protein–protein interaction landscape of human Hippo pathway. Our study provides a glimpse into the global organization of Hippo pathway, reveals previously unknown interactions within this pathway, and uncovers new potential components involved in the regulation of this pathway. Understanding these interactions will help us further dissect the Hippo signaling-pathway and extend our knowledge of organ size control. PMID:24126142

  4. Position- and polarity-dependent Hippo signaling regulates cell fates in preimplantation mouse embryos.

    PubMed

    Sasaki, Hiroshi

    2015-12-01

    During the preimplantation stage, mouse embryos establish two cell lineages by the time of early blastocyst formation: the trophectoderm (TE) and the inner cell mass (ICM). Historical models have proposed that the establishment of these two lineages depends on the cell position within the embryo (e.g., the positional model) or cell polarization along the apicobasal axis (e.g., the polarity model). Recent findings have revealed that the Hippo signaling pathway plays a central role in the cell fate-specification process: active and inactive Hippo signaling in the inner and outer cells promote ICM and TE fates, respectively. Intercellular adhesion activates, while apicobasal polarization suppresses Hippo signaling, and a combination of these processes determines the spatially regulated activation of the Hippo pathway in 32-cell-stage embryos. Therefore, there is experimental evidence in favor of both positional and polarity models. At the molecular level, phosphorylation of the Hippo-pathway component angiomotin at adherens junctions (AJs) in the inner (apolar) cells activates the Lats protein kinase and triggers Hippo signaling. In the outer cells, however, cell polarization sequesters Amot from basolateral AJs and suppresses activation of the Hippo pathway. Other mechanisms, including asymmetric cell division and Notch signaling, also play important roles in the regulation of embryonic development. In this review, I discuss how these mechanisms cooperate with the Hippo signaling pathway during cell fate-specification processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Neutron Time-of-Flight Diffractometer HIPPO at LANSCE

    NASA Astrophysics Data System (ADS)

    Vogel, Sven; Williams, Darrick; Zhao, Yusheng; Bennett, Kristin; von Dreele, Bob; Wenk, Hans-Rudolf

    2004-03-01

    The High-Pressure Preferred Orientation (HIPPO) neutron diffractometer is the first third-generation neutron time-of-flight powder diffractometer to be constructed in the United States. It produces extremely high intensity by virtue of a short (9 m) initial flight path on a high intensity water moderator and 1380 3He detector tubes covering 4.5 m2 of detector area from 10' to 150' in scattering angles. HIPPO was designed and manufactured as a joint effort between LANSCE and University of California with the goals of attaining world-class science and making neutron powder diffractometry an accessible and available tool to the national user community. Over two decades of momentum transfer are available (0.1-30 A-1) to support studies of amorphous solids; magnetic diffraction; small crystalline samples; and samples subjected to extreme environments such as temperature, pressure, or magnetic fields. The exceptionally high data rates of HIPPO also make it useful for time-resolved studies. In addition to the standard ancillary equipment (100-position sample/texture changer, closed-cycle He refrigerator, furnace), HIPPO has unique high-pressure cells capable of achieving pressures of 30 GPA at ambient and high (2000 K) temperature with samples up to 100 mm3 in volume.

  6. A LATS biosensor screen identifies VEGFR as a regulator of the Hippo pathway in angiogenesis.

    PubMed

    Azad, T; Janse van Rensburg, H J; Lightbody, E D; Neveu, B; Champagne, A; Ghaffari, A; Kay, V R; Hao, Y; Shen, H; Yeung, B; Croy, B A; Guan, K L; Pouliot, F; Zhang, J; Nicol, C J B; Yang, X

    2018-03-13

    The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ. We further show that the Hippo pathway is a critical mediator of VEGF-induced angiogenesis and tumor vasculogenic mimicry. Thus, our work offers a biosensor tool for the study of the Hippo pathway and suggests a role for Hippo signaling in regulating blood vessel formation in physiological and pathological settings.

  7. Hippo signaling in the kidney: the good and the bad.

    PubMed

    Wong, Jenny S; Meliambro, Kristin; Ray, Justina; Campbell, Kirk N

    2016-08-01

    The Hippo signaling pathway is an evolutionarily conserved kinase cascade, playing multiple roles in embryonic development that controls organ size, cell proliferation, and apoptosis. At the center of this network lie the Hippo kinase target and downstream pathway effector Yes-associated protein (YAP) and its paralog TAZ. In its phosphorylated form, cytoplasmic YAP is sequestered in an inactive state. When it is dephosphorylated, YAP, a potent oncogene, is activated and relocates to the nucleus to interact with a number of transcription factors and signaling regulators that promote cell growth, differentiation, and survival. The identification of YAP activation in human cancers has made it an attractive target for chemotherapeutic drug development. Little is known to date about the function of the Hippo pathway in the kidney, but that is rapidly changing. Recent studies have shed light on the role of Hippo-YAP signaling in glomerular and lower urinary tract embryonic development, maintenance of podocyte homeostasis, the integrity of the glomerular filtration barrier, regulation of renal tubular cyst growth, renal epithelial injury in diabetes, and renal fibrogenesis. This review summarizes the current knowledge of the Hippo-YAP signaling axis in the kidney under normal and disease conditions. Copyright © 2016 the American Physiological Society.

  8. Jack R. Ferrell III | NREL

    Science.gov Websites

    Jack R. Ferrell III Photo of Jack R. Ferrell III Jack Ferrell Research Engineer Jack.Ferrell @nrel.gov | 303-384-7777 Orcid ID http://orcid.org/0000-0003-3041-8742 Research Interests Jack Ferrell works in the Thermochemical Catalysis Research and Development (R&D) group and manages tasks on

  9. The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications.

    PubMed

    Teoh, Seong Lin; Das, Srijit

    2017-11-30

    The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression. The Hippo pathway (also known as the Salvador-Warts-Hippo pathway) is the latest emerging concept in cancers. The Hippo pathway plays an important role in controlling the size of the tissue and organ by virtue of its action on cell proliferation and apoptosis. In the present review, we highlight the mammalian Hippo pathway, role of its core members, its upstream regulators, downstream effectors and the resistance cases in lung cancers. Specific interaction of Mer with cell surface hyaluronan receptor CD44 is vital in cell contact inhibition, thereby activating Hippo pathway. Both transcription co-activators YAP and TAZ (also known as WWTR1, being homologs of Drosophila Yki) are important regulators of proliferation and apoptosis, and serve as major downstream effectors of the Hippo pathway. Mutation of NF2, the upstream regulator of Hippo pathway is linked to the cancers. Targeting YAP and TAZ may be important for future drug delivery and treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. From Jack to Double Jack Polynomials via the Supersymmetric Bridge

    NASA Astrophysics Data System (ADS)

    Lapointe, Luc; Mathieu, Pierre

    2015-07-01

    The Calogero-Sutherland model occurs in a large number of physical contexts, either directly or via its eigenfunctions, the Jack polynomials. The supersymmetric counterpart of this model, although much less ubiquitous, has an equally rich structure. In particular, its eigenfunctions, the Jack superpolynomials, appear to share the very same remarkable combinatorial and structural properties as their non-supersymmetric version. These super-functions are parametrized by superpartitions with fixed bosonic and fermionic degrees. Now, a truly amazing feature pops out when the fermionic degree is sufficiently large: the Jack superpolynomials stabilize and factorize. Their stability is with respect to their expansion in terms of an elementary basis where, in the stable sector, the expansion coefficients become independent of the fermionic degree. Their factorization is seen when the fermionic variables are stripped off in a suitable way which results in a product of two ordinary Jack polynomials (somewhat modified by plethystic transformations), dubbed the double Jack polynomials. Here, in addition to spelling out these results, which were first obtained in the context of Macdonal superpolynomials, we provide a heuristic derivation of the Jack superpolynomial case by performing simple manipulations on the supersymmetric eigen-operators, rendering them independent of the number of particles and of the fermionic degree. In addition, we work out the expression of the Hamiltonian which characterizes the double Jacks. This Hamiltonian, which defines a new integrable system, involves not only the expected Calogero-Sutherland pieces but also combinations of the generators of an underlying affine {widehat{sl}_2} algebra.

  11. Epigenetic restriction of Hippo signaling by MORC2 underlies stemness of hepatocellular carcinoma cells.

    PubMed

    Wang, Tao; Qin, Zhong-Yi; Wen, Liang-Zhi; Guo, Yan; Liu, Qin; Lei, Zeng-Jie; Pan, Wei; Liu, Kai-Jun; Wang, Xing-Wei; Lai, Shu-Jie; Sun, Wen-Jing; Wei, Yan-Ling; Liu, Lei; Guo, Ling; Chen, Yu-Qin; Wang, Jun; Xiao, Hua-Liang; Bian, Xiu-Wu; Chen, Dong-Feng; Wang, Bin

    2018-03-19

    The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC). We identify a member of the microrchidia (MORC) protein family, MORC2, as an inhibitor of the Hippo pathway by controlling upstream Hippo regulators, neurofibromatosis 2 (NF2) and kidney and brain protein (KIBRA). Mechanistically, MORC2 forms a complex with DNA methyltransferase 3A (DNMT3A) at the promoters of NF2 and KIBRA, leading to their DNA hyper-methylation and transcriptional repression. As a result, NF2 and KIBRA are crucial targets of MORC2 to regulate confluence-induced activation of Hippo signaling and contact inhibition of cell growth under both physiological and pathological conditions. The MORC2-NF2/KIBRA axis is critical for maintaining self-renewal, sorafenib resistance, and oncogenicity of HCC cells in vitro and in nude mice. Furthermore, MORC2 expression is elevated in HCC tissues, associated with stem-like properties of cancer cells, and disease progression in patients. Collectively, MORC2 promotes cancer stemness and tumorigenesis by facilitating DNA methylation-dependent silencing of Hippo signaling and could be a potential molecular target for cancer therapeutics.

  12. Hippo pathway and protection of genome stability in response to DNA damage.

    PubMed

    Pefani, Dafni E; O'Neill, Eric

    2016-04-01

    The integrity of DNA is constantly challenged by exposure to the damaging effects of chemical and physical agents. Elucidating the cellular mechanisms that maintain genomic integrity via DNA repair and cell growth control is vital because errors in these processes lead to genomic damage and the development of cancer. By gaining a deep molecular understanding of the signaling pathways regulating genome integrity it is hoped to uncover new therapeutics and treatment designs to combat cancer. Components of the Hippo pathway, a tumor-suppressor cascade, have recently been defined to limit cancer transformation in response to DNA damage. In this review, we briefly introduce the Hippo signaling cascade in mammals and discuss in detail how the Hippo pathway has been established as part of the DNA damage response, activated by apical signaling kinases that recognize breaks in DNA. We also highlight the significance of the Hippo pathway activator RASSF1A tumor suppressor, a direct target of ataxia telangiectasia mutated and ataxia telangiectasia and Rad3 related ATR. Furthermore we discuss how Hippo pathway in response DNA lesions can induce cell death via Yes-associated protein (YAP) (the canonical Hippo pathway effector) or promote maintenance of genome integrity in a YAP-independent manner. © 2015 FEBS.

  13. YAP and TAZ: a nexus for Hippo signaling and beyond

    PubMed Central

    Guan, Kun-Liang

    2015-01-01

    The Hippo pathway is a potent regulator of cellular proliferation, differentiation, and tissue homeostasis. Here we review the regulatory mechanisms of the Hippo pathway and discuss the function of Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding domain (TAZ), the prime mediators of the Hippo pathway, in stem cell biology and tissue regeneration. We highlight their activities in both the nucleus and the cytoplasm and discuss their role as a signaling nexus and integrator of several other prominent signaling pathways such as the Wnt, G protein-coupled receptor (GPCR), epidermal growth factor (EGF), BMP/transforming growth factor beta (TGFβ), and Notch pathways. PMID:26045258

  14. Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer

    PubMed Central

    Yu, Fa-Xing; Zhao, Bin; Guan, Kun-Liang

    2015-01-01

    Two decades of studies in multiple model organisms have established the Hippo pathway as a key regulator of organ size and tissue homeostasis. By inhibiting YAP and TAZ transcription co-activators, the Hippo pathway regulates cell proliferation, apoptosis, and stemness in response to a wide range of extracellular and intracellular signals, including cell-cell contact, cell polarity, mechanical cues, ligands of G-protein coupled receptors, and cellular energy status. Dysregulation of the Hippo pathway exerts a significant impact on cancer development. Further investigation of the functions and regulatory mechanisms of this pathway will help uncovering the mystery of organ size control and identify new targets for cancer treatment. PMID:26544935

  15. The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Drosophila Ovary

    PubMed Central

    Sarikaya, Didem P.; Extavour, Cassandra G.

    2015-01-01

    The Hippo pathway regulates organ size, stem cell proliferation and tumorigenesis in adult organs. Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size, however, has received little attention. Here, we ask whether Hippo signaling influences the number of stem cell niches that are established during development of the Drosophila larval ovary, and whether it interacts with the same or different effector signaling pathways in different cell types. We demonstrate that canonical Hippo signaling regulates autonomous proliferation of the soma, while a novel hippo-independent activity of Yorkie regulates autonomous proliferation of the germ line. Moreover, we demonstrate that Hippo signaling mediates non-autonomous proliferation signals between germ cells and somatic cells, and contributes to maintaining the correct proportion of these niche precursors. Finally, we show that the Hippo pathway interacts with different growth pathways in distinct somatic cell types, and interacts with EGFR and JAK/STAT pathways to regulate non-autonomous proliferation of germ cells. We thus provide evidence for novel roles of the Hippo pathway in establishing the precise balance of soma and germ line, the appropriate number of stem cell niches, and ultimately regulating adult female reproductive capacity. PMID:25643260

  16. Regulation of the Hippo-YAP Pathway by Glucose Sensor O-GlcNAcylation.

    PubMed

    Peng, Changmin; Zhu, Yue; Zhang, Wanjun; Liao, Qinchao; Chen, Yali; Zhao, Xinyuan; Guo, Qiang; Shen, Pan; Zhen, Bei; Qian, Xiaohong; Yang, Dong; Zhang, Jin-San; Xiao, Dongguang; Qin, Weijie; Pei, Huadong

    2017-11-02

    The Hippo pathway is crucial in organ size control and tissue homeostasis, with deregulation leading to cancer. An extracellular nutrition signal, such as glucose, regulates the Hippo pathway activation. However, the mechanisms are still not clear. Here, we found that the Hippo pathway is directly regulated by the hexosamine biosynthesis pathway (HBP) in response to metabolic nutrients. Mechanistically, the core component of Hippo pathway (YAP) is O-GlcNAcylated by O-GlcNAc transferase (OGT) at serine 109. YAP O-GlcNAcylation disrupts its interaction with upstream kinase LATS1, prevents its phosphorylation, and activates its transcriptional activity. And this activation is not dependent on AMPK. We also identified OGT as a YAP-regulated gene that forms a feedback loop. Finally, we confirmed that glucose-induced YAP O-GlcNAcylation and activation promoted tumorigenesis. Together, our data establish a molecular mechanism and functional significance of the HBP in directly linking extracellular glucose signal to the Hippo-YAP pathway and tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. HOW to Manage Jack Pine to Reduce Damage from Jack Pine Budworm

    Treesearch

    Deborah G. McCullough; Steven Katovich; Robert L. Heyd; Shane Weber

    1994-01-01

    Jack pine budworm, Choristoneura pinus pinus Freeman, is a needle feeding caterpillar that is generally considered the most significant pest of jack pine. Vigorous young jack pine stands are rarely damaged during outbreaks. The most vigorous stands are well stocked, evenly spaced, fairly uniform in height, and less than 45 years old. Stands older than 45 years that are...

  18. Control of proliferation and cancer growth by the Hippo signaling pathway

    PubMed Central

    Ehmer, Ursula; Sage, Julien

    2015-01-01

    The control of cell division is essential for normal development and the maintenance of cellular homeostasis. Abnormal cell proliferation is associated with multiple pathological states, including cancer. While the Hippo/YAP signaling pathway was initially thought to control organ size and growth, increasing evidence indicates that this pathway also plays a major role in the control of proliferation independent of organ size control. In particular, accumulating evidence indicates that the Hippo/YAP signaling pathway functionally interacts with multiple other cellular pathways and serves as a central node in the regulation of cell division, especially in cancer cells. Here recent observations are highlighted that connect Hippo/YAP signaling to transcription, the basic cell cycle machinery, and the control of cell division. Furthermore, the oncogenic and tumor suppressive attributes of YAP/TAZ are reviewed which emphasizes the relevance of the Hippo pathway in cancer. PMID:26432795

  19. YAP and the Hippo pathway in pediatric cancer

    PubMed Central

    Mohamed, Abdalla D.; Gener, Melissa; Li, Weijie; Taboada, Eugenio

    2017-01-01

    ABSTRACT The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell–cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation of Hippo pathway members in several pediatric cancers and may offer prognostic information on rhabdomyosarcoma, osteosarcoma, Wilms tumor, neuroblastoma, medulloblastoma, and other brain gliomas. We review the results of such published studies and highlight the potential clinical application of this pathway in pediatric oncologic and pathologic studies. These studies support targeting this pathway as a novel treatment strategy. PMID:28616573

  20. YAP and the Hippo pathway in pediatric cancer.

    PubMed

    Ahmed, Atif A; Mohamed, Abdalla D; Gener, Melissa; Li, Weijie; Taboada, Eugenio

    2017-01-01

    The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation of Hippo pathway members in several pediatric cancers and may offer prognostic information on rhabdomyosarcoma, osteosarcoma, Wilms tumor, neuroblastoma, medulloblastoma, and other brain gliomas. We review the results of such published studies and highlight the potential clinical application of this pathway in pediatric oncologic and pathologic studies. These studies support targeting this pathway as a novel treatment strategy.

  1. The emerging role of Hippo signaling pathway in regulating osteoclast formation.

    PubMed

    Yang, Wanlei; Han, Weiqi; Qin, An; Wang, Ziyi; Xu, Jiake; Qian, Yu

    2018-06-01

    A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP, and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis. It is revealed that specific molecules of the Hippo-signaling pathway take part in a stage specific regulation in pre-osteoclast proliferation, osteoclast differentiation and osteoclast apoptosis and survival. Upon activation, MST and LAST, transcriptional co-activators YAP and TAZ bind to the members of the TEA domain (TEAD) family transcription factors, and influence osteoclast differentiation via regulating the expression of downstream target genes such as connective tissue growth factor (CTGF/CCN2) and cysteine-rich protein 61 (CYR61/CCN1). In addition, through interacting or cross talking with RANKL-mediated signaling cascades including NF-κB, MAPKs, AP1, and NFATc1, Hippo-signaling molecules such as YAP/TAZ/TEAD complex, RASSF2, MST2, and Ajuba could also potentially modulate osteoclast differentiation and function. Elucidating the roles of the Hippo-signaling pathway in osteoclast development and specific molecules involved is important for understanding the mechanism of bone homeostasis and diseases. © 2017 Wiley Periodicals, Inc.

  2. Control of Organ Growth by Patterning and Hippo Signaling in Drosophila

    PubMed Central

    Irvine, Kenneth D.; Harvey, Kieran F.

    2015-01-01

    Control of organ size is of fundamental importance and is controlled by genetic, environmental, and mechanical factors. Studies in many species have pointed to the existence of both organ-extrinsic and -intrinsic size-control mechanisms, which ultimately must coordinate to regulate organ size. Here, we discuss organ size control by organ patterning and the Hippo pathway, which both act in an organ-intrinsic fashion. The influence of morphogens and other patterning molecules couples growth and patterning, whereas emerging evidence suggests that the Hippo pathway controls growth in response to mechanical stimuli and signals emanating from cell–cell interactions. Several points of cross talk have been reported between signaling pathways that control organ patterning and the Hippo pathway, both at the level of membrane receptors and transcriptional regulators. However, despite substantial progress in the past decade, key questions in the growth-control field remain, including precisely how and when organ patterning and the Hippo pathway communicate to control size, and whether these communication mechanisms are organ specific or general. In addition, elucidating mechanisms by which organ-intrinsic cues, such as patterning factors and the Hippo pathway, interface with extrinsic cues, such as hormones to control organ size, remain unresolved. PMID:26032720

  3. The Hippo pathway in heart development, regeneration, and diseases

    PubMed Central

    Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

    2015-01-01

    The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes due to injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is very limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/ progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein (YAP) transcription co-activator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor (GPCR) signaling, and oxidative stress, are known to play critical roles in cardiac physiology. In addition, YAP has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings regarding the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. PMID:25858067

  4. The hippo pathway in heart development, regeneration, and diseases.

    PubMed

    Zhou, Qi; Li, Li; Zhao, Bin; Guan, Kun-Liang

    2015-04-10

    The heart is the first organ formed during mammalian development. A properly sized and functional heart is vital throughout the entire lifespan. Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality. Unfortunately, regenerative potential of the adult heart is limited. The Hippo pathway is a recently identified signaling cascade that plays an evolutionarily conserved role in organ size control by inhibiting cell proliferation, promoting apoptosis, regulating fates of stem/progenitor cells, and in some circumstances, limiting cell size. Interestingly, research indicates a key role of this pathway in regulation of cardiomyocyte proliferation and heart size. Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration. Several known upstream signals of the Hippo pathway such as mechanical stress, G-protein-coupled receptor signaling, and oxidative stress are known to play critical roles in cardiac physiology. In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms. In this review, we summarize and discuss current findings on the roles and mechanisms of the Hippo pathway in heart development, injury, and regeneration. © 2015 American Heart Association, Inc.

  5. The Hippo pathway in hepatocellular carcinoma: Non-coding RNAs in action.

    PubMed

    Shi, Xuan; Zhu, Hai-Rong; Liu, Tao-Tao; Shen, Xi-Zhong; Zhu, Ji-Min

    2017-08-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide. However, current strategies curing HCC are far from satisfaction. The Hippo pathway is an evolutionarily conserved tumor suppressive pathway that plays crucial roles in organ size control and tissue homeostasis. Its dysregulation is commonly observed in various types of cancer including HCC. Recently, the prominent role of non-coding RNAs in the Hippo pathway during normal development and neoplastic progression is also emerging in liver. Thus, further investigation into the regulatory network between non-coding RNAs and the Hippo pathway and their connections with HCC may provide new therapeutic avenues towards developing an effective preventative or perhaps curative treatment for HCC. Herein we summarize the role of non-coding RNAs in the Hippo pathway, with an emphasis on their contribution to carcinogenesis, diagnosis, treatment and prognosis of HCC. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Identifying pelagic fish eggs in the southeast Yucatan Peninsula using DNA barcodes.

    PubMed

    Leyva-Cruz, E; Vásquez-Yeomans, L; Carrillo, L; Valdez-Moreno, M

    2016-12-01

    In the waters surrounding Banco Chinchorro in the Mexican Caribbean are spawning and nursery areas for many types of fish. In this natural environment, as opposed to under controlled laboratory conditions, it is almost impossible to link an individual egg to the adult that laid it. This makes identifying the species of the eggs difficult. However, DNA barcodes have made this easier. In the present study, 300 eggs were processed for molecular analysis, from which 139 sequences were obtained. We identified 42 taxa (33 species with their binomial names), 35 genera, and 24 families. The identified eggs included those from Ariomma melanum, which is the first recording of this species in the Mexican Caribbean. Eggs from economically important fish species were also identified, including frigate tuna (Auxis thazard), crevalle jack (Caranx hippos), common dolphinfish (Coryphaena hippurus), sailfish (Istiophorus platypterus), white marlin (Kajikia albida), skipjack tuna (Katsuwonus pelamis), blackfin tuna (Thunnus atlanticus), and swordfish (Xiphias gladius). We have also described new morphological characteristics and captured photographs for 21 species, as well as obtained new information about spawning locality and time for 16 species. This valuable information will provide the basis to develop more effective conservation measures for sustainable fisheries and protection of the Mesoamerican Barrier Reef System.

  7. Inactivation of Hippo Pathway Is Significantly Associated with Poor Prognosis in Hepatocellular Carcinoma.

    PubMed

    Sohn, Bo Hwa; Shim, Jae-Jun; Kim, Sang-Bae; Jang, Kyu Yun; Kim, Soo Mi; Kim, Ji Hoon; Hwang, Jun Eul; Jang, Hee-Jin; Lee, Hyun-Sung; Kim, Sang-Cheol; Jeong, Woojin; Kim, Sung Soo; Park, Eun Sung; Heo, Jeonghoon; Kim, Yoon Jun; Kim, Dae-Ghon; Leem, Sun-Hee; Kaseb, Ahmed; Hassan, Manal M; Cha, Minse; Chu, In-Sun; Johnson, Randy L; Park, Yun-Yong; Lee, Ju-Seog

    2016-03-01

    The Hippo pathway is a tumor suppressor in the liver. However, the clinical significance of Hippo pathway inactivation in HCC is not clearly defined. We analyzed genomic data from human and mouse tissues to determine clinical relevance of Hippo pathway inactivation in HCC. We analyzed gene expression data from Mst1/2(-/-) and Sav1(-/-) mice and identified a 610-gene expression signature reflecting Hippo pathway inactivation in the liver [silence of Hippo (SOH) signature]. By integrating gene expression data from mouse models with those from human HCC tissues, we developed a prediction model that could identify HCC patients with an inactivated Hippo pathway and used it to test its significance in HCC patients, via univariate and multivariate Cox analyses. HCC patients (National Cancer Institute cohort, n = 113) with the SOH signature had a significantly poorer prognosis than those without the SOH signature [P < 0.001 for overall survival (OS)]. The significant association of the signature with poor prognosis was further validated in the Korean (n = 100, P = 0.006 for OS) and Fudan University cohorts (n = 242, P = 0.001 for OS). On multivariate analysis, the signature was an independent predictor of recurrence-free survival (HR, 1.6; 95% confidence interval, 1.12-2.28: P = 0.008). We also demonstrated significant concordance between the SOH HCC subtype and the hepatic stem cell HCC subtype that had been identified in a previous study (P < 0.001). Inactivation of the Hippo pathway in HCC is significantly associated with poor prognosis. ©2015 American Association for Cancer Research.

  8. SCFSlmb E3 ligase-mediated degradation of Expanded is inhibited by the Hippo pathway in Drosophila

    PubMed Central

    Zhang, Hongtao; Li, Changqing; Chen, Hanqing; Wei, Chuanxian; Dai, Fei; Wu, Honggang; Dui, Wen; Deng, Wu-Min; Jiao, Renjie

    2015-01-01

    Deregulation of the evolutionarily conserved Hippo pathway has been implicated in abnormal development of animals and in several types of cancer. One mechanism of Hippo pathway regulation is achieved by controlling the stability of its regulatory components. However, the executive E3 ligases that are involved in this process, and how the process is regulated, remain poorly defined. In this study, we identify, through a genetic candidate screen, the SCFSlmb E3 ligase as a novel negative regulator of the Hippo pathway in Drosophila imaginal tissues via mediation of the degradation of Expanded (Ex). Mechanistic study shows that Slmb-mediated degradation of Ex is inhibited by the Hippo signaling. Considering the fact that Hippo signaling suppresses the transcription of ex, we propose that the Hippo pathway employs a double security mechanism to ensure fine-tuned homeostasis during development. PMID:25522691

  9. The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

    PubMed Central

    Fallahi, Emma; O’Driscoll, Niamh A.; Matallanas, David

    2016-01-01

    The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. PMID:27322327

  10. Jack & the Video Camera

    ERIC Educational Resources Information Center

    Charlan, Nathan

    2010-01-01

    This article narrates how the use of video camera has transformed the life of Jack Williams, a 10-year-old boy from Colorado Springs, Colorado, who has autism. The way autism affected Jack was unique. For the first nine years of his life, Jack remained in his world, alone. Functionally non-verbal and with motor skill problems that affected his…

  11. TEAD1 mediates the oncogenic activities of Hippo-YAP1 signaling in osteosarcoma.

    PubMed

    Chai, Jiwei; Xu, Shijie; Guo, Fengbo

    2017-06-24

    Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS. Genetic silencing of TEAD1 suppressed multiple malignant phenotypes of OS cells including cell proliferation, apoptosis resistance, and invasive potential. Mechanistically, we showed that TEAD1 largely exerted its transcriptional control of its functional targets, PTGS2 and CYR61. Collectively, this work identifies the YAP1/TEAD1 complex as the representative dysregulated profile of Hippo signaling in OS and provides proof-of-principle that targeting TEAD1 may be a therapeutic strategy of osteosarcoma. Copyright © 2017. Published by Elsevier Inc.

  12. Endocardial Hippo signaling regulates myocardial growth and cardiogenesis.

    PubMed

    Artap, Stanley; Manderfield, Lauren J; Smith, Cheryl L; Poleshko, Andrey; Aghajanian, Haig; See, Kelvin; Li, Li; Jain, Rajan; Epstein, Jonathan A

    2018-08-01

    The Hippo signaling pathway has been implicated in control of cell and organ size, proliferation, and endothelial-mesenchymal transformation. This pathway impacts upon two partially redundant transcription cofactors, Yap and Taz, that interact with other factors, including members of the Tead family, to affect expression of downstream genes. Yap and Taz have been shown to regulate, in a cell-autonomous manner, myocardial proliferation, myocardial hypertrophy, regenerative potential, and overall size of the heart. Here, we show that Yap and Taz also play an instructive, non-cell-autonomous role in the endocardium of the developing heart to regulate myocardial growth through release of the paracrine factor, neuregulin. Without endocardial Yap and Taz, myocardial growth is impaired causing early post-natal lethality. Thus, the Hippo signaling pathway regulates cell size via both cell-autonomous and non-cell-autonomous mechanisms. Furthermore, these data suggest that Hippo may regulate organ size via a sensing and paracrine function in endothelial cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Motorized support jack

    DOEpatents

    Haney, Steven J.; Herron, Donald Joe

    2003-05-13

    A compact, vacuum compatible motorized jack for supporting heavy loads and adjusting their positions is provided. The motorized jack includes: (a) a housing having a base; (b) a first roller device that provides a first slidable surface and that is secured to the base; (c) a second roller device that provides a second slidable surface and that has an upper surface; (d) a wedge that is slidably positioned between the first roller device and the second roller device so that the wedge is in contact with the first slidable surface and the second slidable surface; (e) a motor; and (d) a drive mechanism that connects the motor and the wedge to cause the motor to controllably move the wedge forwards or backwards. Individual motorized jacks can support and lift of an object at an angle. Two or more motorized jacks can provide tip, tilt and vertical position adjustment capabilities.

  14. Motorized support jack

    DOEpatents

    Haney, Steven J.; Herron, Donald Joe

    2001-01-01

    A compact, vacuum compatible motorized jack for supporting heavy loads and adjusting their positions is provided. The motorized jack includes: (a) a housing having a base; (b) a first roller device that provides a first slidable surface and that is secured to the base; (c) a second roller device that provides a second slidable surface and that has an upper surface; (d) a wedge that is slidably positioned between the first roller device and the second roller device so that the wedge is in contact with the first slidable surface and the second slidable surface; (e) a motor; and (d) a drive mechanism that connects the motor and the wedge to cause the motor to controllably move the wedge forwards or backwards. Individual motorized jacks can support and lift of an object at an angle. Two or more motorized jacks can provide tip, tilt and vertical position adjustment capabilities.

  15. Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest.

    PubMed

    Manderfield, Lauren J; Aghajanian, Haig; Engleka, Kurt A; Lim, Lillian Y; Liu, Feiyan; Jain, Rajan; Li, Li; Olson, Eric N; Epstein, Jonathan A

    2015-09-01

    Notch signaling has well-defined roles in the assembly of arterial walls and in the development of the endothelium and smooth muscle of the vasculature. Hippo signaling regulates cellular growth in many tissues, and contributes to regulation of organ size, in addition to other functions. Here, we show that the Notch and Hippo pathways converge to regulate smooth muscle differentiation of the neural crest, which is crucial for normal development of the aortic arch arteries and cranial vasculature during embryonic development. Neural crest-specific deletion of the Hippo effectors Yap and Taz produces neural crest precursors that migrate normally, but fail to produce vascular smooth muscle, and Notch target genes such as Jagged1 fail to activate normally. We show that Yap is normally recruited to a tissue-specific Jagged1 enhancer by directly interacting with the Notch intracellular domain (NICD). The Yap-NICD complex is recruited to chromatin by the DNA-binding protein Rbp-J in a Tead-independent fashion. Thus, Hippo signaling can modulate Notch signaling outputs, and components of the Hippo and Notch pathways physically interact. Convergence of Hippo and Notch pathways by the mechanisms described here might be relevant for the function of these signaling cascades in many tissues and in diseases such as cancer. © 2015. Published by The Company of Biologists Ltd.

  16. Stable MOB1 interaction with Hippo/MST is not essential for development and tissue growth control.

    PubMed

    Kulaberoglu, Yavuz; Lin, Kui; Holder, Maxine; Gai, Zhongchao; Gomez, Marta; Assefa Shifa, Belul; Mavis, Merdiye; Hoa, Lily; Sharif, Ahmad A D; Lujan, Celia; Smith, Ewan St John; Bjedov, Ivana; Tapon, Nicolas; Wu, Geng; Hergovich, Alexander

    2017-09-25

    The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction. By studying these variants in human cancer cells and Drosophila, we uncovered that MOB1/Warts binding is essential for tumor suppression, tissue growth control, and development, while stable MOB1/Hippo binding is dispensable and MOB1/Trc binding alone is insufficient. Collectively, we decrypt molecularly, cell biologically, and genetically the importance of the diverse interactions of Hippo core kinases with the pivotal MOB1 signal transducer.The Hippo tumor suppressor pathway is essential for development and tissue growth control. Here the authors employ a multi-disciplinary approach to characterize the interactions of the three Hippo kinases with the signaling adaptor MOB1 and show how they differently affect development, tissue growth and tumor suppression.

  17. Molecular chaperone Hsp27 regulates the Hippo tumor suppressor pathway in cancer.

    PubMed

    Vahid, Sepideh; Thaper, Daksh; Gibson, Kate F; Bishop, Jennifer L; Zoubeidi, Amina

    2016-08-24

    Heat shock protein 27 (Hsp27) is a molecular chaperone highly expressed in aggressive cancers, where it is involved in numerous pro-tumorigenic signaling pathways. Using functional genomics we identified for the first time that Hsp27 regulates the gene signature of transcriptional co-activators YAP and TAZ, which are negatively regulated by the Hippo Tumor Suppressor pathway. The Hippo pathway inactivates YAP by phosphorylating and increasing its cytoplasmic retention with the 14.3.3 proteins. Gain and loss of function experiments in prostate, breast and lung cancer cells showed that Hsp27 knockdown induced YAP phosphorylation and cytoplasmic localization while overexpression of Hsp27 displayed opposite results. Mechanistically, Hsp27 regulates the Hippo pathway by accelerating the proteasomal degradation of ubiquitinated MST1, the core Hippo kinase, resulting in reduced phosphorylation/activity of LATS1 and MOB1, its downstream effectors. Importantly, our in vitro results were supported by data from human tumors; clinically, high expression of Hsp27 in prostate tumors is correlated with increased expression of YAP gene signature and reduced phosphorylation of YAP in lung and invasive breast cancer clinical samples. This study reveals for the first time a link between Hsp27 and the Hippo cascade, providing a novel mechanism of deregulation of this tumor suppressor pathway across multiple cancers.

  18. G protein-coupled receptors: bridging the gap from the extracellular signals to the Hippo pathway.

    PubMed

    Zhou, Xin; Wang, Zhen; Huang, Wei; Lei, Qun-Ying

    2015-01-01

    The Hippo pathway is crucial in organ size control, whereas its dysregulation contributes to organ degeneration or tumorigenesis. The kinase cascade of MST1/2 and LATS1/2 and the coupling transcription co-activators YAP/TAZ represent the core components of the Hippo pathway. Extensive studies have identified a number of upstream regulators of the Hippo pathway, including contact inhibition, mechanic stress, extracellular matrix stiffness, cytoskeletal rearrangement, and some molecules of cell polarity and cell junction. However, how the diffuse extracellular signals regulate the Hippo pathway puzzles the researchers for a long time. Unexpectedly, recent elegant studies demonstrated that stimulation of some G protein-coupled receptors (GPCRs), such as lysophosphatidic acid receptor, sphingosine-1-phosphate receptor, and the protease activated receptor PAR1, causes potent YAP/TAZ dephosphorylation and activation by promoting actin cytoskeleton assemble. In this review, we briefly describe the components of the Hippo pathway and focus on the recent progress with respect to the regulation of the Hippo pathway by GPCRs and G proteins in cancer cells. In addition, we also discuss the potential therapeutic roles targeting the Hippo pathway in human cancers. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

  19. Jacks--A Study of Simple Machines.

    ERIC Educational Resources Information Center

    Parsons, Ralph

    This vocational physics individualized student instructional module on jacks (simple machines used to lift heavy objects) contains student prerequisites and objectives, an introduction, and sections on the ratchet bumper jack, the hydraulic jack, the screw jack, and load limitations. Designed with a laboratory orientation, each section consists of…

  20. Regulation of Tissue Growth by the Mammalian Hippo Signaling Pathway

    PubMed Central

    Watt, Kevin I.; Harvey, Kieran F.; Gregorevic, Paul

    2017-01-01

    The integrative control of diverse biological processes such as proliferation, differentiation, apoptosis and metabolism is essential to maintain cellular and tissue homeostasis. Disruption of these underlie the development of many disease states including cancer and diabetes, as well as many of the complications that arise as a consequence of aging. These biological outputs are governed by many cellular signaling networks that function independently, and in concert, to convert changes in hormonal, mechanical and metabolic stimuli into alterations in gene expression. First identified in Drosophila melanogaster as a powerful mediator of cell division and apoptosis, the Hippo signaling pathway is a highly conserved regulator of mammalian organ size and functional capacity in both healthy and diseased tissues. Recent studies have implicated the pathway as an effector of diverse physiological cues demonstrating an essential role for the Hippo pathway as an integrative component of cellular homeostasis. In this review, we will: (a) outline the critical signaling elements that constitute the mammalian Hippo pathway, and how they function to regulate Hippo pathway-dependent gene expression and tissue growth, (b) discuss evidence that shows this pathway functions as an effector of diverse physiological stimuli and (c) highlight key questions in this developing field. PMID:29225579

  1. HIPPO Experiment Data Access and Subseting System

    NASA Astrophysics Data System (ADS)

    Krassovski, Misha; Hook, Les; Christensen, Sigurd; Boden, Tom

    2014-05-01

    HIAPER Pole-to-Pole Observations (HIPPO) was an NSF- and NOAA-funded, multi-year global airborne research project to survey the latitudinal and vertical distribution of greenhouse and related gases, and aerosols. Project scientists and support staff flew five month-long missions over the Pacific Basin on the NSF/NCAR Gulfstream V, High-performance Instrumented Airborne Platform for Environmental Research (HIAPER) aircraft between January 2009 and September 2011, spread throughout the annual cycle, from the surface to 14 km in altitude, and from 87N to 67S. The landmark study resulted in an extensive, highly detailed dataset of over 90 atmospheric species, from six categories, all with navigation and atmospheric structure data, including greenhouse gases and carbon cycle gases; ozone and water vapor; black carbon and aerosols; ozone-depleting substances and their replacements; light hydrocarbons and PAN; and sulfur gases/ocean-derived gases. A suite of specialized instruments on the aircraft made high-rate measurements as the plane flew, while several whole air samplers collected flasks of air for later analysis in laboratories around the U.S. Flights were conducted in a continuously profiling mode, with the aircraft alternately climbing or descending as it flew from its home base in Broomfield, Colorado north to Alaska and the Arctic, south down the middle of the Pacific Ocean to New Zealand and the Southern Ocean near Antarctica, and then back to the Arctic a second time before returning home. In all, the aircraft made 64 flights and flew 787 vertical profiles while covering 285,000 km. Instruments collected 434 hours of high-rate continuous measurements and 4,235 flask samples were collected during the five HIPPO missions. Data from the HIPPO study of greenhouse gases and aerosols are now available to the atmospheric research community and the public. This comprehensive dataset provides the first high-resolution vertically resolved measurements of over 90 unique

  2. PAR1 participates in the ability of multidrug resistance and tumorigenesis by controlling Hippo-YAP pathway.

    PubMed

    Fujimoto, Daisuke; Ueda, Yuki; Hirono, Yasuo; Goi, Takanori; Yamaguchi, Akio

    2015-10-27

    The Hippo pathway significantly correlates with organ size control and tumorigenesis. The activity of YAP/TAZ, a transducer of the Hippo pathway, is required to sustain self-renewal and tumor-initiation capacities in cancer stem cells (CSCs). But, upstream signals that control the mammalian Hippo pathway have not been well understood. Here, we reveal a connection between the Protease-activated receptor 1 (PAR1) signaling pathway and the Hippo-YAP pathway in gastric cancer stem-like cells. The selective PAR1 agonist TFLLR-NH2 induces an increase in the fraction of side population cells which is enriched in CSCs, and promotes tumorigenesis, multi cancer drug resistance, cell morphological change, and cell invasion which are characteristics of CSCs. In addition, PAR1 activation inhibits the Hippo-YAP pathway kinase Lats via Rho GTPase. Lats kinase inhibition in turn results in increased nuclear localization of dephosphorylated YAP. Furthermore, PAR1 activation confers CSCs related traits via the Hippo-YAP pathway, and the Hippo-YAP pathway correlates with epithelial mesenchymal transition which is induced by PAR1 activation. Our research suggests that the PAR1 signaling deeply participates in the ability of multi drug resistance and tumorigenesis through interactions with the Hippo-YAP pathway signaling in gastric cancer stem-like cells. We presume that inhibited YAP is a new therapeutic target in the treatment human gastric cancer invasion and metastasis by dysregulated PAR1 or its agonists.

  3. Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer.

    PubMed

    Yimlamai, Dean; Fowl, Brendan H; Camargo, Fernando D

    2015-12-01

    The Hippo pathway and its regulatory target, YAP, has recently emerged as an important biochemical signaling pathway that tightly governs epithelial tissue growth. Initially defined in Drosophilia, this pathway has shown remarkable conservation in vertebrate systems with many components of the Hippo/YAP pathway showing biochemical and functional conservation. The liver is particularly sensitive to changes in Hippo/YAP signaling with rapid increases in liver size becoming manifest on the order of days to weeks after perturbation. The first identified direct targets of Hippo/YAP signaling were pro-proliferative and anti-apoptotic gene programs, but recent work has now implicated this pathway in cell fate choice, stem cell maintenance/renewal, epithelial to mesenchymal transition, and oncogenesis. The mechanisms by which Hippo/YAP signaling is changed endogenously are beginning to come to light as well as how this pathway interacts with other signaling pathways, and important details for designing new therapeutic interventions. This review focuses on the known roles for Hippo/YAP signaling in the liver and promising avenues for future study. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  4. Molecular chaperone Hsp27 regulates the Hippo tumor suppressor pathway in cancer

    PubMed Central

    Vahid, Sepideh; Thaper, Daksh; Gibson, Kate F.; Bishop, Jennifer L.; Zoubeidi, Amina

    2016-01-01

    Heat shock protein 27 (Hsp27) is a molecular chaperone highly expressed in aggressive cancers, where it is involved in numerous pro-tumorigenic signaling pathways. Using functional genomics we identified for the first time that Hsp27 regulates the gene signature of transcriptional co-activators YAP and TAZ, which are negatively regulated by the Hippo Tumor Suppressor pathway. The Hippo pathway inactivates YAP by phosphorylating and increasing its cytoplasmic retention with the 14.3.3 proteins. Gain and loss of function experiments in prostate, breast and lung cancer cells showed that Hsp27 knockdown induced YAP phosphorylation and cytoplasmic localization while overexpression of Hsp27 displayed opposite results. Mechanistically, Hsp27 regulates the Hippo pathway by accelerating the proteasomal degradation of ubiquitinated MST1, the core Hippo kinase, resulting in reduced phosphorylation/activity of LATS1 and MOB1, its downstream effectors. Importantly, our in vitro results were supported by data from human tumors; clinically, high expression of Hsp27 in prostate tumors is correlated with increased expression of YAP gene signature and reduced phosphorylation of YAP in lung and invasive breast cancer clinical samples. This study reveals for the first time a link between Hsp27 and the Hippo cascade, providing a novel mechanism of deregulation of this tumor suppressor pathway across multiple cancers. PMID:27555231

  5. Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2.

    PubMed

    Zhang, Shihao; Chen, Qinghua; Liu, Qingxu; Li, Yuxi; Sun, Xiufeng; Hong, Lixin; Ji, Suyuan; Liu, Chengyan; Geng, Jing; Zhang, Weiji; Lu, Zhonglei; Yin, Zhen-Yu; Zeng, Yuanyuan; Lin, Kwang-Huei; Wu, Qiao; Li, Qiyuan; Nakayama, Keiko; Nakayama, Keiich I; Deng, Xianming; Johnson, Randy L; Zhu, Liang; Gao, Daming; Chen, Lanfen; Zhou, Dawang

    2017-05-08

    Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis. Importantly, the depletion or inactivation of Akt or Skp2 abrogated Hippo signal deficiency-induced liver tumorigenesis, indicating their epistatic interaction. Thus, we conclude that Hippo-Yap signaling suppresses cell polyploidy and oncogenesis through Skp2. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Rheb may complex with RASSF1A to coordinate Hippo and TOR signaling.

    PubMed

    Nelson, Nicholas; Clark, Geoffrey J

    2016-06-07

    The TOR pathway is a vital component of cellular homeostasis that controls the synthesis of proteins, nucleic acids and lipids. Its core is the TOR kinase. Activation of the TOR pathway suppresses autophagy, which plays a vital but complex role in tumorigenesis. The TOR pathway is regulated by activation of the Ras-related protein Rheb, which can bind mTOR. The Hippo pathway is a major growth control module that regulates cell growth, differentiation and apoptosis. Its core consists of an MST/LATS kinase cascade that can be activated by the RASSF1A tumor suppressor. The TOR and Hippo pathways may be coordinately regulated to promote cellular homeostasis. However, the links between the pathways remain only partially understood. We now demonstrate that in addition to mTOR regulation, Rheb also impacts the Hippo pathway by forming a complex with RASSF1A. Using stable clones of two human lung tumor cell lines (NCI-H1792 and NCI-H1299) with shRNA-mediated silencing or ectopic overexpression of RASSF1A, we show that activated Rheb stimulates the Hippo pathway, but is suppressed in its ability to stimulate the TOR pathway. Moreover, by selectively labeling autophagic vacuoles we show that RASSF1A inhibits the ability of Rheb to suppress autophagy and enhance cell growth. Thus, we identify a new connection that impacts coordination of Hippo and TOR signaling. As RASSF1A expression is frequently lost in human tumors, the RASSF1A status of a tumor may impact not just its Hippo pathway status, but also its TOR pathway status.

  7. Rho differentially regulates the Hippo pathway by modulating the interaction between Amot and Nf2 in the blastocyst.

    PubMed

    Shi, Xianle; Yin, Zixi; Ling, Bin; Wang, Lingling; Liu, Chang; Ruan, Xianhui; Zhang, Weiyu; Chen, Lingyi

    2017-11-01

    The Hippo pathway modulates the transcriptional activity of Yap to regulate the differentiation of the inner cell mass (ICM) and the trophectoderm (TE) in blastocysts. Yet how Hippo signaling is differentially regulated in ICM and TE cells is poorly understood. Through an inhibitor/activator screen, we have identified Rho as a negative regulator of Hippo in TE cells, and PKA as a positive regulator of Hippo in ICM cells. We further elucidated a novel mechanism by which Rho suppresses Hippo, distinct from the prevailing view that Rho inhibits Hippo signaling through modulating cytoskeleton remodeling and/or cell polarity. Active Rho prevents the phosphorylation of Amot Ser176, thus stabilizing the interaction between Amot and F-actin, and restricting the binding between Amot and Nf2. Moreover, Rho attenuates the interaction between Amot and Nf2 by binding to the coiled-coil domain of Amot. By blocking the association of Nf2 and Amot, Rho suppresses Hippo in TE cells. © 2017. Published by The Company of Biologists Ltd.

  8. Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma.

    PubMed

    Sekido, Yoshitaka

    2018-03-22

    Malignant mesothelioma (MM) constitutes a very aggressive tumor that arises from the pleural or peritoneal cavities and is highly refractory to conventional therapies. Several key genetic alterations are associated with the development and progression of MM including mutations of the CDKN2A/ARF , NF2 , and BAP1 tumor-suppressor genes. Notably, activating oncogene mutations are very rare; thus, it is difficult to develop effective inhibitors to treat MM. The NF2 gene encodes merlin, a protein that regulates multiple cell-signaling cascades including the Hippo pathway. MMs also exhibit inactivation of Hippo pathway components including LATS1/2, strongly suggesting that merlin-Hippo pathway dysregulation plays a key role in the development and progression of MM. Furthermore, Hippo pathway inactivation has been shown to result in constitutive activation of the YAP1/TAZ transcriptional coactivators, thereby conferring malignant phenotypes to mesothelial cells. Critical YAP1/TAZ target genes, including prooncogenic CCDN1 and CTGF , have also been shown to enhance the malignant phenotypes of MM cells. Together, these data indicate the Hippo pathway as a therapeutic target for the treatment of MM, and support the development of new strategies to effectively target the activation status of YAP1/TAZ as a promising therapeutic modality for this formidable disease.

  9. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals.

    PubMed

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2017-07-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development.

  10. The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

    PubMed Central

    Wu, Nan; Nguyen, Quy; Wan, Ying; Zhou, Tiaohao; Venter, Julie; Frampton, Gabriel A; DeMorrow, Sharon; Pan, Duojia; Meng, Fanyin; Glaser, Shannon; Alpini, Gianfranco; Bai, Haibo

    2018-01-01

    The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice. However, it remains to be determined whether the Hippo signaling pathway functions through the Notch signaling in intrahepatic bile duct development. We found that loss of the Hippo signaling pathway tumor suppressor Nf2 resulted in increased expression levels of the Notch signaling pathway receptor Notch2 in cholangiocytes but not in hepatocytes. When knocking down Notch2 on the background of Nf2 deficiency in mouse livers, the excessive bile duct development induced by Nf2 deficiency was suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results implicated that Notch signaling is one of the downstream effectors of the Hippo signaling pathway in regulating intrahepatic bile duct development. PMID:28581486

  11. Maniac Talk - Dr. Jack Kaye

    NASA Image and Video Library

    2014-07-23

    Jack Kaye Maniac Lecture, July 23, 2014 Dr. Jack Kaye, Associate Director for Research at NASA Headquarters presented a Maniac Talk entitled, "An Unlikely but Rewarding Journey--From Quantum Chemistry to Earth Science Research Program Leadership." Jack took stock of his 30+ years at NASA, noting the people, opportunities, lessons learned, and choices that helped him get to where he is today and accomplish what he have.

  12. Taiman acts as a coactivator of Yorkie in the Hippo pathway to promote tissue growth and intestinal regeneration.

    PubMed

    Wang, Chao; Yin, Meng-Xin; Wu, Wei; Dong, Liang; Wang, Shimin; Lu, Yi; Xu, Jinjin; Wu, Wenqing; Li, Sheng; Zhao, Yun; Zhang, Lei

    2016-01-01

    The Hippo signaling pathway regulates tissue growth and organ size through controlling cell growth, proliferation and apoptosis. During these processes, the coactivator Yorkie partners with the transcription factor Scalloped to mediate Hippo pathway-regulated cellular functions. Here, we demonstrate that Taiman facilitates the activity of Yorkie. First, Taiman overexpression upregulates Hippo pathway-responsive genes and induces tissue overgrowth. Second, the loss of tai downregulates the expression of Hippo pathway target genes and reduces organ size as well as tissue overgrowth caused by Yorkie overexpression. Furthermore, we provide evidence that Taiman binds to Yorkie and facilitates the activity of Yorkie-Scalloped to activate the transcription of several Hippo pathway target genes. Moreover, we found that the C-terminus of Taiman is indispensable for the function of Taiman in Hippo signaling. Finally, we demonstrate that Taiman is also required in intestinal stem cell proliferation. Our findings suggest Taiman is an essential coactivator of Yorkie.

  13. The Steroid Hormone 20-Hydroxyecdysone Up-regulates Ste-20 Family Serine/Threonine Kinase Hippo to Induce Programmed Cell Death*

    PubMed Central

    Dong, Du-Juan; Jing, Yu-Pu; Liu, Wen; Wang, Jin-Xing; Zhao, Xiao-Fan

    2015-01-01

    The steroid hormone 20-hydroxyecdysone (20E) and the serine/threonine Ste20-like kinase Hippo signal promote programmed cell death (PCD) during development, although the interaction between them remains unclear. Here, we present evidence that 20E up-regulates Hippo to induce PCD during the metamorphic development of insects. We found that Hippo is involved in 20E-induced metamorphosis via promoting the phosphorylation and cytoplasmic retention of Yorkie (Yki), causing suppressed expression of the inhibitor of apoptosis (IAP), thereby releasing its inhibitory effect on caspase. Furthermore, we show that 20E induced the expression of Hippo at the transcriptional level through the ecdysone receptor (EcR), ultraspiracle protein (USP), and hormone receptor 3 (HR3). We also found that Hippo suppresses the binding of Yki complex to the HR3 promoter. In summary, 20E up-regulates the transcription of Hippo via EcRB1, USP1, and HR3 to induce PCD, and Hippo has negative feedback effects on HR3 expression. These two signaling pathways coordinate PCD during insect metamorphosis. PMID:26272745

  14. Using HIPPO Data for Formal and Informal Science Education

    NASA Astrophysics Data System (ADS)

    Rockwell, A.; Hatheway, B.; Zondlo, M. A.

    2012-12-01

    The HIAPER Pole-to-Pole Observations (HIPPO) field project recently concluded its mission to map greenhouse gases and black carbon from the Arctic to the Antarctic using the NSF/NCAR Gulfstream V. HIPPO resulted in visually-rich and easy-to-understand altitude/latitude curtain plots of several trace gases and black carbon, from five seasons during 2009-2011. The data and curtain plots are available for both formal and informal science education to support the instruction of atmospheric science and Earth systems. Middle and high school activities have been developed using these data and curtain plots, and an undergraduate course based on HIPPO data - Global Air Pollution - is offered at Princeton University. The visually stimulating curtain plots are unique in that a wide range of people can comprehend them because they provide an easy-to-understand picture of the global distribution of chemical species for non-scientists or beginning users, while also displaying valuable detailed information for the advanced viewer. The plots are a powerful graphical tool that can be used to communicate climate science because they illustrate the concepts of how trace gas distributions are linked to the large-scale dynamics of the Earth; show seasonal changes in distribution and concentrations; and use the same display format for each tracer. In order to connect people to the data, a multi-faceted and engaging public information program and supporting educational materials for HIPPO were developed. These provided a unique look into global field research and included social media platforms such as Facebook and Twitter; a range of videos from simple motion graphics to detailed narratives; both printed and online written materials; and mass-media publications.

  15. Hippo pathway deficiency reverses systolic heart failure after infarction.

    PubMed

    Leach, John P; Heallen, Todd; Zhang, Min; Rahmani, Mahdis; Morikawa, Yuka; Hill, Matthew C; Segura, Ana; Willerson, James T; Martin, James F

    2017-10-12

    Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.

  16. Jack Dymond's Deep Insights

    NASA Astrophysics Data System (ADS)

    Thomson, R. E.; Delaney, J. R.

    2004-12-01

    Most people do not know that Jack Dymond was a major influence on several aspects of current deep-sea research. Along with Margaret Leinen and Jack, we were part of the first Alvin dive program on the Endeavour hydrothermal field in 1984. Jack was working with Rick, on a sediment-trap study of the overall carbon fluxes in the vicinity of the Endeavour hydrothermal systems in an effort to address a question that Cindy Lee had posed about the overall carbon production from hydrothermal vents. At the time we were recognizing and naming many of the 20- to 40-meter-high sulfide structures in the Endeavour field (Hulk, Grotto, Dante, Dudley, Bastille), Jack commented that it was a shame that the world could not see these magnificent edifices or watch endlessly awesome black smokers. His feeling was that some vent sites should be converted to National Parks to preserve them from invasion by enthusiastic scientists, yet he clearly had the vision that the public should be given a sense of the grandeur involved locally, as well as the vastness of the 70,000-km ridge-crest system running through every ocean. Within a year we started talking about the RIDGE Program, and Jack was an early and enthusiastic participant in the design and development of RIDGE. Jack was among the first to encourage multi-disciplinary research at the hydrothermal vent sites. Recognizing that deep currents are important to vent processes, he urged physical oceanographers to work with the chemists, biologists, and geologists and was personally responsible for Rick becoming interested in studying vents. We, the co-authors of this abstract, became close friends as a result of having been introduced to each other by Jack. Several years ago, we co-authored the first paper ever written on the possible influence of hydrothermal activity on the circulation of the Europan Ocean, a paper that we here dedicate to the memory of Jack. Finally, it was in part because of Jack's conviction that the world should know

  17. Cross-Talk Between Mitochondrial Fusion and the Hippo Pathway in Controlling Cell Proliferation During Drosophila Development.

    PubMed

    Deng, Qiannan; Guo, Ting; Zhou, Xiu; Xi, Yongmei; Yang, Xiaohang; Ge, Wanzhong

    2016-08-01

    Cell proliferation and tissue growth depend on the coordinated regulation of multiple signaling molecules and pathways during animal development. Previous studies have linked mitochondrial function and the Hippo signaling pathway in growth control. However, the underlying molecular mechanisms are not fully understood. Here we identify a Drosophila mitochondrial inner membrane protein ChChd3 as a novel regulator for tissue growth. Loss of ChChd3 leads to tissue undergrowth and cell proliferation defects. ChChd3 is required for mitochondrial fusion and removal of ChChd3 increases mitochondrial fragmentation. ChChd3 is another mitochondrial target of the Hippo pathway, although it is only partially required for Hippo pathway-mediated overgrowth. Interestingly, lack of ChChd3 leads to inactivation of Hippo activity under normal development, which is also dependent on the transcriptional coactivator Yorkie (Yki). Furthermore, loss of ChChd3 induces oxidative stress and activates the JNK pathway. In addition, depletion of other mitochondrial fusion components, Opa1 or Marf, inactivates the Hippo pathway as well. Taken together, we propose that there is a cross-talk between mitochondrial fusion and the Hippo pathway, which is essential in controlling cell proliferation and tissue homeostasis in Drosophila. Copyright © 2016 by the Genetics Society of America.

  18. John B. "Jack" Townshend (1927-2012)

    USGS Publications Warehouse

    Love, Jeffrey J.; Finn, Carol A.

    2012-01-01

    Jack Townshend, geophysicist and dedicated public servant, died on 13 August 2012 in Fairbanks, Alaska. He was 85. Jack's career with the federal government, most of it with the national magnetic observatory program, spanned more than six solar cycles of time, and he retired only days before his death. The duration of Jack's career encompassed an important period in the history of the advancement of our understanding of the Earth. Jack's career of contributions, his life, and his personality are worthy of retrospective celebration.

  19. Hippo signaling regulates Microprocessor and links cell density-dependent miRNA biogenesis to cancer

    PubMed Central

    Mori, Masaki; Triboulet, Robinson; Mohseni, Morvarid; Schlegelmilch, Karin; Shrestha, Kriti; Camargo, Fernando D.; Gregory, Richard I.

    2014-01-01

    SUMMARY Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. PMID:24581491

  20. Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2 expression to modulate host immune responses.

    PubMed

    Boro, Monoranjan; Singh, Vikas; Balaji, Kithiganahalli Narayanaswamy

    2016-11-24

    Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner. Mtb-triggered Hippo signaling modulates the expression and secretion of chemokines (CXCL1 and CXCL2); as silencing MST1/2 compromised the ability of Mtb to furnish the same. Further insight into the mechanism of Hippo-mediated regulation of chemokines revealed the role for a non-canonical Hippo effector interferon (IFN) regulatory factor (IRF) 3 in the process and marked the effect to be independent of LATS1. Alongside their ability to guide directed recruitment of immune cells, we have uncovered a paracrine role for Hippo-mediated secretion of CXCL1 and CXCL2 in the production of anti-microbial peptides (beta-defensins), iNOS, NOX2 and pro-inflammatory molecules during mycobacterial infection of the host. This study highlights the involvement of TLR2-IRAK1/4-MST1/2-IRF3 axis in Mtb-triggered modulation of chemokines and identifies Hippo signaling as a novel regulator of host-mycobacterial interactions.

  1. Dysregulation of YAP by the Hippo pathway is involved in intervertebral disc degeneration, cell contact inhibition, and cell senescence.

    PubMed

    Zhang, Cong; Wang, Feng; Xie, Zhiyang; Chen, Lu; Sinkemani, Arjun; Yu, Haomin; Wang, Kun; Mao, Lu; Wu, Xiaotao

    2018-01-05

    The Hippo pathway plays important roles in wound healing, tissue repair and regeneration, and in the treatment of degenerative diseases, by regulating cell proliferation and apoptosis in mammals. Intervertebral disc degeneration (IDD) is one of the major causes of low back pain, a widespread issue associated with a heavy economic burden. However, the mechanism underlying how the Hippo pathway regulates IDD is not well understood. Here, we demonstrate that the Hippo pathway is involved in natural IDD. Activation and dephosphorylation of yes-associated protein (YAP) were observed in younger rat discs, and decreased gradually with age. Surprisingly, Hippo pathway suppression was accompanied by overexpression of YAP, caused by acute disc injury, suggesting a limited ability for self-repair in IDD. We also demonstrated that YAP is inhibited by cell-to-cell contact via the Hippo pathway in vitro . Phosphorylation by large tumor suppressor kinases 1/2 (LATS1/2) led to cytoplasmic translocation and inactivation of YAP. YAP dephosphorylation was mainly localized in the nucleus and regulated by the Hippo pathway, whereas YAP dephosphorylation occurred in the cytoplasm and was associated with nucleus pulposus cell (NPC) senescence. Moreover, NPCs were transfected with shYAP and it accelerates the premature senescence of cells by interfered Hippo pathway through YAP. Therefore, our results indicate that the Hippo pathway plays an important role in maintaining the homeostasis of intervertebral discs and controlling NPC proliferation.

  2. The Steroid Hormone 20-Hydroxyecdysone Up-regulates Ste-20 Family Serine/Threonine Kinase Hippo to Induce Programmed Cell Death.

    PubMed

    Dong, Du-Juan; Jing, Yu-Pu; Liu, Wen; Wang, Jin-Xing; Zhao, Xiao-Fan

    2015-10-09

    The steroid hormone 20-hydroxyecdysone (20E) and the serine/threonine Ste20-like kinase Hippo signal promote programmed cell death (PCD) during development, although the interaction between them remains unclear. Here, we present evidence that 20E up-regulates Hippo to induce PCD during the metamorphic development of insects. We found that Hippo is involved in 20E-induced metamorphosis via promoting the phosphorylation and cytoplasmic retention of Yorkie (Yki), causing suppressed expression of the inhibitor of apoptosis (IAP), thereby releasing its inhibitory effect on caspase. Furthermore, we show that 20E induced the expression of Hippo at the transcriptional level through the ecdysone receptor (EcR), ultraspiracle protein (USP), and hormone receptor 3 (HR3). We also found that Hippo suppresses the binding of Yki complex to the HR3 promoter. In summary, 20E up-regulates the transcription of Hippo via EcRB1, USP1, and HR3 to induce PCD, and Hippo has negative feedback effects on HR3 expression. These two signaling pathways coordinate PCD during insect metamorphosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Trophic flow structure of a neotropical estuary in northeastern Brazil and the comparison of ecosystem model indicators of estuaries

    NASA Astrophysics Data System (ADS)

    Lira, Alex; Angelini, Ronaldo; Le Loc'h, François; Ménard, Frédéric; Lacerda, Carlos; Frédou, Thierry; Lucena Frédou, Flávia

    2018-06-01

    We developed an Ecopath model for the Estuary of Sirinhaém River (SIR), a small-sized system surrounded by mangroves, subject to high impact, mainly by the sugar cane and other farming industries in order to describe the food web structure and trophic interactions. In addition, we compared our findings with those of 20 available Ecopath estuarine models for tropical, subtropical and temperate regions, aiming to synthesize the knowledge on trophic dynamics and provide a comprehensive analysis of the structures and functioning of estuaries. Our model consisted of 25 compartments and its indicators were within the expected range for estuarine areas around the world. The average trophic transfer efficiency for the entire system was 11.8%, similar to the theoretical value of 10%. The Keystone Index and MTI (Mixed Trophic Impact) analysis indicated that the snook (Centropomus undecimalis and Centropomus parallelus) and jack (Caranx latus and Caranx hippos) are considered as key resources in the system, revealing their high impact in the food web. Both groups have a high ecological and commercial relevance, despite the unregulated fisheries. As result of the comparison of ecosystem model indicators in estuaries, differences in the ecosystem structure from the low latitude zones (tropical estuaries) to the high latitude zones (temperate system) were noticed. The structure of temperate and sub-tropical estuaries is based on high flows of detritus and export, while tropical systems have high biomass, respiration and consumption rates. Higher values of System Omnivory Index (SOI) and Overhead (SO) were observed in the tropical and subtropical estuaries, denoting a more complex food chain. Globally, none of the estuarine models were classified as fully mature ecosystems, although the tropical ecosystems were considered more mature than the subtropical and temperate ecosystems. This study is an important contribution to the trophic modeling of estuaries, which may also help

  4. Dynamic Fluctuations in Subcellular Localization of the Hippo Pathway Effector Yorkie In Vivo.

    PubMed

    Manning, Samuel A; Dent, Lucas G; Kondo, Shu; Zhao, Ziqing W; Plachta, Nicolas; Harvey, Kieran F

    2018-05-21

    The Hippo pathway is an evolutionarily conserved signaling network that integrates diverse cues to control organ size and cell fate. The central downstream pathway protein in Drosophila is the transcriptional co-activator Yorkie (YAP and TAZ in humans), which regulates gene expression with the Scalloped/TEA domain family member (TEAD) transcription factors [1-8]. A central regulatory step in the Hippo pathway is phosphorylation of Yorkie by the NDR family kinase Warts, which promotes Yorkie cytoplasmic localization by stimulating association with 14-3-3 proteins [9-12]. Numerous reports have purported a static model of Hippo signaling whereby, upon Hippo activation, Yorkie/YAP/TAZ become cytoplasmic and therefore inactive, and upon Hippo repression, Yorkie/YAP/TAZ transit to the nucleus and are active. However, we have little appreciation for the dynamics of Yorkie/YAP/TAZ subcellular localization because most studies have been performed in fixed cells and tissues. To address this, we used live multiphoton microscopy to investigate the dynamics of an endogenously tagged Yorkie-Venus protein in growing epithelial organs. We found that the majority of Yorkie rapidly traffics between the cytoplasm and nucleus, rather than being statically localized in either compartment. In addition, discrete cell populations within the same organ display different rates of Yorkie nucleo-cytoplasmic shuttling. By assessing Yorkie dynamics in warts mutant tissue, we found that the Hippo pathway regulates Yorkie subcellular distribution by regulating its rate of nuclear import. Furthermore, Yorkie's localization fluctuates dramatically throughout the cell cycle, being predominantly cytoplasmic during interphase and, unexpectedly, chromatin enriched during mitosis. Yorkie's association with mitotic chromatin is Scalloped dependent, suggesting a potential role in mitotic bookmarking. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. The insulator protein BEAF-32 is required for Hippo pathway activity in the terminal differentiation of neuronal subtypes.

    PubMed

    Jukam, David; Viets, Kayla; Anderson, Caitlin; Zhou, Cyrus; DeFord, Peter; Yan, Jenny; Cao, Jinshuai; Johnston, Robert J

    2016-07-01

    The Hippo pathway is crucial for not only normal growth and apoptosis but also cell fate specification during development. What controls Hippo pathway activity during cell fate specification is incompletely understood. In this article, we identify the insulator protein BEAF-32 as a regulator of Hippo pathway activity in Drosophila photoreceptor differentiation. Though morphologically uniform, the fly eye is composed of two subtypes of R8 photoreceptor neurons defined by expression of light-detecting Rhodopsin proteins. In one R8 subtype, active Hippo signaling induces Rhodopsin 6 (Rh6) and represses Rhodopsin 5 (Rh5), whereas in the other subtype, inactive Hippo signaling induces Rh5 and represses Rh6. The activity state of the Hippo pathway in R8 cells is determined by the expression of warts, a core pathway kinase, which interacts with the growth regulator melted in a double-negative feedback loop. We show that BEAF-32 is required for expression of warts and repression of melted Furthermore, BEAF-32 plays a second role downstream of Warts to induce Rh6 and prevent Rh5 fate. BEAF-32 is dispensable for Warts feedback, indicating that BEAF-32 differentially regulates warts and Rhodopsins. Loss of BEAF-32 does not noticeably impair the functions of the Hippo pathway in eye growth regulation. Our study identifies a context-specific regulator of Hippo pathway activity in post-mitotic neuronal fate, and reveals a developmentally specific role for a broadly expressed insulator protein. © 2016. Published by The Company of Biologists Ltd.

  6. HIPPO Unit Commitment Version 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    2017-01-17

    Developed for the Midcontinent Independent System Operator, Inc. (MISO), HIPPO-Unit Commitment Version 1 is for solving security constrained unit commitment problem. The model was developed to solve MISO's cases. This version of codes includes I/O module to read in MISO's csv files, modules to create a state-based mixed integer programming formulation for solving MIP, and modules to test basic procedures to solve MIP via HPC.

  7. Wnt, RSPO and Hippo Signalling in the Intestine and Intestinal Stem Cells.

    PubMed

    Kriz, Vitezslav; Korinek, Vladimir

    2018-01-08

    In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling. There is growing evidence for multiple crosstalk between Hippo and Wnt/β-catenin signalling. In the ON state, Hippo signalling results in serine/threonine phosphorylation of Yes-associated protein (YAP1) and tafazzin (TAZ), promoting formation of the β-catenin destruction complex. In contrast, YAP1 or TAZ dephosphorylation (and YAP1 methylation) results in β-catenin destruction complex deactivation and β-catenin nuclear localization. In the Hippo OFF state, YAP1 and TAZ are engaged with the nuclear β-catenin and participate in the β-catenin-dependent transcription program. Interestingly, YAP1/TAZ are dispensable for intestinal homeostasis; however, upon Wnt pathway hyperactivation, the proteins together with TEA domain (TEAD) transcription factors drive the transcriptional program essential for intestinal cell transformation. In addition, in many CRC cells, YAP1 phosphorylation by YES proto-oncogene 1 tyrosine kinase (YES1) leads to the formation of a transcriptional complex that includes YAP1, β-catenin and T-box 5 (TBX5) DNA-binding protein. YAP1/β-catenin/T-box 5-mediated transcription is necessary for CRC cell proliferation and survival. Interestingly, dishevelled (DVL) appears to be an important mediator involved in both Wnt and Hippo (YAP1/TAZ) signalling and some of the DVL functions were assigned to the nuclear DVL

  8. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

    PubMed Central

    Osinski, Adam; Tomchick, Diana R; Brautigam, Chad A

    2017-01-01

    The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex. PMID:29063833

  9. Hippo signaling pathway in liver and pancreas: the potential drug target for tumor therapy.

    PubMed

    Kong, Delin; Zhao, Yicheng; Men, Tong; Teng, Chun-Bo

    2015-02-01

    Cell behaviors, including proliferation, differentiation and apoptosis, are intricately controlled during organ development and tissue regeneration. In the past 9 years, the Hippo signaling pathway has been delineated to play critical roles in organ size control, tissue regeneration and tumorigenesis through regulating cell behaviors. In mammals, the core modules of the Hippo signaling pathway include the MST1/2-LATS1/2 kinase cascade and the transcriptional co-activators YAP/TAZ. The activity of YAP/TAZ is suppressed by cytoplasmic retention due to phosphorylation in the canonical MST1/2-LATS1/2 kinase cascade-dependent manner or the non-canonical MST1/2- and/or LATS1/2-independent manner. Hippo signaling pathway, which can be activated or inactivated by cell polarity, contact inhibition, mechanical stretch and extracellular factors, has been demonstrated to be involved in development and tumorigenesis of liver and pancreas. In addition, we have summarized several small molecules currently available that can target Hippo-YAP pathway for potential treatment of hepatic and pancreatic cancers, providing clues for other YAP initiated cancers therapy as well.

  10. Position- and Hippo signaling-dependent plasticity during lineage segregation in the early mouse embryo

    PubMed Central

    Posfai, Eszter; Petropoulos, Sophie; de Barros, Flavia Regina Oliveira; Schell, John Paul; Jurisica, Igor; Sandberg, Rickard; Lanner, Fredrik; Rossant, Janet

    2017-01-01

    The segregation of the trophectoderm (TE) from the inner cell mass (ICM) in the mouse blastocyst is determined by position-dependent Hippo signaling. However, the window of responsiveness to Hippo signaling, the exact timing of lineage commitment and the overall relationship between cell commitment and global gene expression changes are still unclear. Single-cell RNA sequencing during lineage segregation revealed that the TE transcriptional profile stabilizes earlier than the ICM and prior to blastocyst formation. Using quantitative Cdx2-eGFP expression as a readout of Hippo signaling activity, we assessed the experimental potential of individual blastomeres based on their level of Cdx2-eGFP expression and correlated potential with gene expression dynamics. We find that TE specification and commitment coincide and occur at the time of transcriptional stabilization, whereas ICM cells still retain the ability to regenerate TE up to the early blastocyst stage. Plasticity of both lineages is coincident with their window of sensitivity to Hippo signaling. DOI: http://dx.doi.org/10.7554/eLife.22906.001 PMID:28226240

  11. Comparative study of Hippo pathway genes in cellular conveyor belts of a ctenophore and a cnidarian.

    PubMed

    Coste, Alicia; Jager, Muriel; Chambon, Jean-Philippe; Manuel, Michaël

    2016-01-01

    The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with subsequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non-model animal species and notably none in non-bilaterian phyla. All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydrozoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle "cellular conveyor belts" of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely proliferate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere. This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell proliferation in a cnidarian, strongly evoking the cell division-promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and regulation of Hippo pathway genes between cnidarians and ctenophores.

  12. Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.

    PubMed

    Mehra, Rohit; Vats, Pankaj; Cieslik, Marcin; Cao, Xuhong; Su, Fengyun; Shukla, Sudhanshu; Udager, Aaron M; Wang, Rui; Pan, Jincheng; Kasaian, Katayoon; Lonigro, Robert; Siddiqui, Javed; Premkumar, Kumpati; Palapattu, Ganesh; Weizer, Alon; Hafez, Khaled S; Wolf, J Stuart; Sangoi, Ankur R; Trpkov, Kiril; Osunkoya, Adeboye O; Zhou, Ming; Giannico, Giovanna; McKenney, Jesse K; Dhanasekaran, Saravana M; Chinnaiyan, Arul M

    2016-11-01

    Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma (RCC) with distinctive morphologic and cytogenetic features. Here, we carry out whole-exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n = 22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSG) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes, whereas other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to biallelic alterations in these TSGs. As a readout of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation. MTSCC is a rare and relatively recently described subtype of RCC. Next-generation sequencing of a multi-institutional MTSCC cohort revealed recurrent chromosomal losses and somatic mutations in the Hippo signaling pathway genes leading to potential YAP1 activation. In virtually all cases of MTSCC, there was evidence of Hippo pathway dysregulation, suggesting a common mechanistic basis for this disease. Cancer Discov; 6(11); 1258-66. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 1197. ©2016 American Association for Cancer Research.

  13. Rho-associated protein kinase regulates subcellular localisation of Angiomotin and Hippo-signalling during preimplantation mouse embryo development.

    PubMed

    Mihajlović, Aleksandar I; Bruce, Alexander W

    2016-09-01

    The differential activity of the Hippo-signalling pathway between the outer- and inner-cell populations of the developing preimplantation mouse embryo directs appropriate formation of trophectoderm and inner cell mass (ICM) lineages. Such distinct signalling activity is under control of intracellular polarization, whereby Hippo-signalling is either supressed in polarized outer cells or activated in apolar inner cells. The central role of apical-basolateral polarization to such differential Hippo-signalling regulation prompted us to reinvestigate the role of potential upstream molecular regulators affecting apical-basolateral polarity. This study reports that the chemical inhibition of Rho-associated kinase (Rock) is associated with failure to form morphologically distinct blastocysts, indicative of compromised trophectoderm differentiation, and defects in the localization of both apical and basolateral polarity factors associated with malformation of tight junctions. Moreover, Rock-inhibition mediates mislocalization of the Hippo-signalling activator Angiomotin (Amot), to the basolateral regions of outer cells and is concomitant with aberrant activation of the pathway. The Rock-inhibition phenotype is mediated by Amot, as RNAi-based Amot knockdown totally rescues the normal suppression of Hippo-signalling in outer cells. In conclusion, Rock, via regulating appropriate apical-basolateral polarization in outer cells, regulates the appropriate activity of the Hippo-signalling pathway, by ensuring correct subcellular localization of Amot protein in outer cells. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  14. The HIAPER Pole-to-Pole Observations (HIPPO) Public Data Archive at CDIAC: Carbon Cycle and Greenhouse Gas Data

    NASA Astrophysics Data System (ADS)

    Christensen, S. W.; Hook, L. A.

    2011-12-01

    The HIAPER Pole-to-Pole Observations (HIPPO) project is investigating the carbon cycle and greenhouse gases throughout various altitudes in the atmosphere over the Pacific Basin through the annual cycle (Wofsy and the HIPPO Science Team 2011, this session). Aircraft-based data collection occurred during 2009-2011. Data analyses, comparisons, and integration are ongoing. A permanent public archive of HIPPO data has been established at the U. S. DOE Carbon Dioxide Information Analysis Center (CDIAC). Datasets are provided primarily by the Lead Principal Investigator (PI), who draws on a comprehensive set of aircraft navigation information, meteorological measurements, and research instrument and sampling system results from multiple co-investigators to compile integrated and generate value-added products. A website/ftp site has been developed for HIPPO data and metadata (http://hippo.ornl.gov), in coordination with the UCAR website that presents field catalogs and other detailed information about HIPPO missions (http://www.eol.ucar.edu/projects/hippo/dm/). A data policy was adopted that balances the needs of the project investigators with the interests of the scientific user community. A data dictionary was developed to capture the basic characteristics of the hundreds of measurements. Instrument descriptions were compiled. A user's guide is presented for each dataset that also contains data file information enabling users to know when data have been updated. Data are received and provided as space-delimited ASCII files. Metadata records are compiled into a searchable CDIAC index and will be submitted to climate change research data clearinghouses. Each dataset is given a persistent identifier (DOI) to facilitate attribution. We expect that data will continue to be added to the archive for the next year or more. In the future we anticipate creating a database for HIPPO data, with a web interface to facilitate searching and customized data extraction.

  15. Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway.

    PubMed

    Chen, Meiyuan; Wang, Min; Xu, Simiao; Guo, Xingjun; Jiang, Jianxin

    2015-12-29

    The Hippo signaling pathway plays a crucial role in regulating tissue homeostasis, organ size, tumorigenesis and cancer chemoresistance when deregulated. Physiologically, the Hippo core kinase cassette that consists of mamma-lian STE20-like protein kinase 1/2 (MST1/2), and large tumour suppressor 1/2 (LATS1/2), together with the adaptor proteins Salvador homologue 1 (SAV1) and MOB kinase activator 1 (MOB1), tightly restricts the activities of homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) to low levels. However, how the Hippo kinase cassette core components are simultaneously inhibited, to exhibit constitutively inactivated Hippo signaling and activated YAP/TAZ in cancer remains puzzling. Herein, we reported that miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-181c in the progression of pancreatic cancer, but also may represent a new therapeutic target and prognostic marker.

  16. Alternative Splicing in the Hippo Pathway—Implications for Disease and Potential Therapeutic Targets

    PubMed Central

    Porazinski, Sean; Ladomery, Michael

    2018-01-01

    Alternative splicing is a well-studied gene regulatory mechanism that produces biological diversity by allowing the production of multiple protein isoforms from a single gene. An involvement of alternative splicing in the key biological signalling Hippo pathway is emerging and offers new therapeutic avenues. This review discusses examples of alternative splicing in the Hippo pathway, how deregulation of these processes may contribute to disease and whether these processes offer new potential therapeutic targets. PMID:29534050

  17. SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase STRIPAK

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bae, Sung Jun; Ni, Lisheng; Osinski, Adam

    The Hippo pathway controls tissue growth and homeostasis through a central MST-LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this kinase cascade, but the molecular mechanisms remain unknown. Here, we discover SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation loop. Our structural and biochemical studies reveal that SAV1 and MST2 heterodimerize through their SARAH domains. Two SAV1–MST2 heterodimers further dimerize through SAV1 WW domains to form a heterotetramer, in which MST2 undergoes trans-autophosphorylation. SAV1more » directly binds to STRIPAK and inhibits its phosphatase activity, protecting MST2 activation-loop phosphorylation. Genetic ablation of SLMAP in human cells leads to spontaneous activation of the Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1 promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase complex.« less

  18. The Hippo component YAP localizes in the nucleus of human papilloma virus positive oropharyngeal squamous cell carcinoma.

    PubMed

    Alzahrani, Faisal; Clattenburg, Leanne; Muruganandan, Shanmugam; Bullock, Martin; MacIsaac, Kaitlyn; Wigerius, Michael; Williams, Blair A; Graham, M Elise R; Rigby, Matthew H; Trites, Jonathan R B; Taylor, S Mark; Sinal, Christopher J; Fawcett, James P; Hart, Robert D

    2017-02-22

    HPV infection causes cervical cancer, mediated in part by the degradation of Scribble via the HPV E6 oncoprotein. Recently, Scribble has been shown to be an important regulator of the Hippo signaling cascade. Deregulation of the Hippo pathway induces an abnormal cellular transformation, epithelial to mesenchymal transition, which promotes oncogenic progression. Given the recent rise in oropharyngeal HPV squamous cell carcinoma we sought to determine if Hippo signaling components are implicated in oropharyngeal squamous cell carcinoma. Molecular and cellular techniques including immunoprecipiations, Western blotting and immunocytochemistry were used to identify the key Hippo pathway effector Yes-Associated Protein (YAP)1. Oropharyngeal tissue was collected from CO 2 laser resections, and probed with YAP1 antibody in tumor and pre-malignant regions of HPV positive OPSCC tissue. This study reveals that the Scribble binding protein Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP) forms a complex with YAP. Further, the NOS1APa and NOS1APc isoforms show differential association with activated and non-activated YAP, and impact cellular proliferation. Consistent with deregulated Hippo signaling in OPSCC HPV tumors, we see a delocalization of Scribble and increased nuclear accumulation of YAP1 in an HPV-positive OPSCC. Our preliminary data indicates that NOS1AP isoforms differentially associate with YAP1, which, together with our previous findings, predicts that loss of YAP1 enhances cellular transformation. Moreover, YAP1 is highly accumulated in the nucleus of HPV-positive OPSCC, implying that Hippo signaling and possibly NOS1AP expression are de-regulated in OPSCC. Further studies will help determine if NOS1AP isoforms, Scribble and Hippo components will be useful biomarkers in OPSCC tumor biology.

  19. 46 CFR 134.150 - Liftboat-jacking systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Liftboat-jacking systems. 134.150 Section 134.150... FOR LIFTBOATS § 134.150 Liftboat-jacking systems. (a) For this subchapter, liftboat jacking systems are vital systems and must comply with Sections 4/1.13.1 through 4/1.13.3 of the ABS's “Rules for...

  20. 46 CFR 134.150 - Liftboat-jacking systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Liftboat-jacking systems. 134.150 Section 134.150... FOR LIFTBOATS § 134.150 Liftboat-jacking systems. (a) For this subchapter, liftboat jacking systems are vital systems and must comply with Sections 4/1.13.1 through 4/1.13.3 of the ABS's “Rules for...

  1. Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage

    PubMed Central

    Cao, Zubing; Carey, Timothy S.; Ganguly, Avishek; Wilson, Catherine A.; Paul, Soumen; Knott, Jason G.

    2015-01-01

    Cell fate decisions are fundamental to the development of multicellular organisms. In mammals the first cell fate decision involves segregation of the pluripotent inner cell mass and the trophectoderm, a process regulated by cell polarity proteins, HIPPO signaling and lineage-specific transcription factors such as CDX2. However, the regulatory mechanisms that operate upstream to specify the trophectoderm lineage have not been established. Here we report that transcription factor AP-2γ (TFAP2C) functions as a novel upstream regulator of Cdx2 expression and position-dependent HIPPO signaling in mice. Loss- and gain-of-function studies and promoter analysis revealed that TFAP2C binding to an intronic enhancer is required for activation of Cdx2 expression during early development. During the 8-cell to morula transition TFAP2C potentiates cell polarity to suppress HIPPO signaling in the outside blastomeres. TFAP2C depletion triggered downregulation of PARD6B, loss of apical cell polarity, disorganization of F-actin, and activation of HIPPO signaling in the outside blastomeres. Rescue experiments using Pard6b mRNA restored cell polarity but only partially corrected position-dependent HIPPO signaling, suggesting that TFAP2C negatively regulates HIPPO signaling via multiple pathways. Several genes involved in regulation of the actin cytoskeleton (including Rock1, Rock2) were downregulated in TFAP2C-depleted embryos. Inhibition of ROCK1 and ROCK2 activity during the 8-cell to morula transition phenocopied TFAP2C knockdown, triggering a loss of position-dependent HIPPO signaling and decrease in Cdx2 expression. Altogether, these results demonstrate that TFAP2C facilitates trophectoderm lineage specification by functioning as a key regulator of Cdx2 transcription, cell polarity and position-dependent HIPPO signaling. PMID:25858457

  2. Transcription factor AP-2γ induces early Cdx2 expression and represses HIPPO signaling to specify the trophectoderm lineage.

    PubMed

    Cao, Zubing; Carey, Timothy S; Ganguly, Avishek; Wilson, Catherine A; Paul, Soumen; Knott, Jason G

    2015-05-01

    Cell fate decisions are fundamental to the development of multicellular organisms. In mammals the first cell fate decision involves segregation of the pluripotent inner cell mass and the trophectoderm, a process regulated by cell polarity proteins, HIPPO signaling and lineage-specific transcription factors such as CDX2. However, the regulatory mechanisms that operate upstream to specify the trophectoderm lineage have not been established. Here we report that transcription factor AP-2γ (TFAP2C) functions as a novel upstream regulator of Cdx2 expression and position-dependent HIPPO signaling in mice. Loss- and gain-of-function studies and promoter analysis revealed that TFAP2C binding to an intronic enhancer is required for activation of Cdx2 expression during early development. During the 8-cell to morula transition TFAP2C potentiates cell polarity to suppress HIPPO signaling in the outside blastomeres. TFAP2C depletion triggered downregulation of PARD6B, loss of apical cell polarity, disorganization of F-actin, and activation of HIPPO signaling in the outside blastomeres. Rescue experiments using Pard6b mRNA restored cell polarity but only partially corrected position-dependent HIPPO signaling, suggesting that TFAP2C negatively regulates HIPPO signaling via multiple pathways. Several genes involved in regulation of the actin cytoskeleton (including Rock1, Rock2) were downregulated in TFAP2C-depleted embryos. Inhibition of ROCK1 and ROCK2 activity during the 8-cell to morula transition phenocopied TFAP2C knockdown, triggering a loss of position-dependent HIPPO signaling and decrease in Cdx2 expression. Altogether, these results demonstrate that TFAP2C facilitates trophectoderm lineage specification by functioning as a key regulator of Cdx2 transcription, cell polarity and position-dependent HIPPO signaling. © 2015. Published by The Company of Biologists Ltd.

  3. Generalized clustering conditions of Jack polynomials at negative Jack parameter {alpha}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bernevig, B. Andrei; Department of Physics, Princeton University, Princeton, New Jersey 08544; Haldane, F. D. M.

    We present several conjectures on the behavior and clustering properties of Jack polynomials at a negative parameter {alpha}=-(k+1/r-1), with partitions that violate the (k,r,N)- admissibility rule of [Feigin et al. [Int. Math. Res. Notices 23, 1223 (2002)]. We find that the ''highest weight'' Jack polynomials of specific partitions represent the minimum degree polynomials in N variables that vanish when s distinct clusters of k+1 particles are formed, where s and k are positive integers. Explicit counting formulas are conjectured. The generalized clustering conditions are useful in a forthcoming description of fractional quantum Hall quasiparticles.

  4. The HIPPO Project Archive: Carbon Cycle and Greenhouse Gas Data

    NASA Astrophysics Data System (ADS)

    Christensen, S. W.; Aquino, J.; Hook, L.; Williams, S. F.

    2012-12-01

    The HIAPER (NSF/NCAR Gulfstream V Aircraft) Pole-to-Pole Observations (HIPPO) project measured a comprehensive suite of atmospheric trace gases and aerosols pertinent to understanding the global carbon cycle from the surface to the tropopause and approximately pole-to-pole over the Pacific Ocean. Flights took place over five missions during different seasons from 2009 to 2011. Data and documentation are available to the public from two archives: (1) NCAR's Earth Observing Laboratory (EOL) provides complete aircraft and flight operational data, and (2) the U.S. DOE's Carbon Dioxide Information Analysis Center (CDIAC) provides integrated measurement data products. The integrated products are more generally useful for secondary analyses. Data processing is nearing completion, although improvements to the data will continue to evolve and analyses will continue many years into the future. Periodic new releases of integrated measurement (merged) products will be generated by EOL when individual measurement data have been updated as directed by the Lead Principal Investigator. The EOL and CDIAC archives will share documentation and supplemental links and will ensure that the latest versions of data products are available to users of both archives. The EOL archive (http://www.eol.ucar.edu/projects/hippo/) provides the underlying investigator-provided data, including supporting data sets (e.g. operational satellite, model output, global observations, etc.), and ancillary flight operational information including field catalogs, data quality reports, software, documentation, publications, photos/imagery, and other detailed information about the HIPPO missions. The CDIAC archive provides integrated measurement data products, user documentation, and metadata through the HIPPO website (http://hippo.ornl.gov). These merged products were derived by consistently combining the aircraft state parameters for position, time, temperature, pressure, and wind speed with meteorological

  5. Fire effects in northeastern forests: jack pine.

    Treesearch

    Cary Rouse

    1986-01-01

    The jack pine ecosystem has evolved through fire. Jack pine, although easily killed by fire, has developed serotinous cones that depend upon high heat to open and release the seeds. Without a fire to enable the cones to open, jack pine would be replaced by another species. Prescribed fire can be an economical management tool for site preparation in either a natural...

  6. A role for Hippo/YAP-signaling in FGF-induced lens epithelial cell proliferation and fibre differentiation.

    PubMed

    Dawes, L J; Shelley, E J; McAvoy, J W; Lovicu, F J

    2018-04-01

    Recent studies indicate an important role for the transcriptional co-activator Yes-associated protein (YAP), and its regulatory pathway Hippo, in controlling cell growth and fate during lens development; however, the exogenous factors that promote this pathway are yet to be identified. Given that fibroblast growth factor (FGF)-signaling is an established regulator of lens cell behavior, the current study investigates the relationship between this pathway and Hippo/YAP-signaling during lens cell proliferation and fibre differentiation. Rat lens epithelial explants were cultured with FGF2 to induce epithelial cell proliferation or fibre differentiation. Immunolabeling methods were used to detect the expression of Hippo-signaling components, Total and Phosphorylated YAP, as well as fibre cell markers, Prox-1 and β-crystallin. FGF-induced lens cell proliferation was associated with a strong nuclear localisation of Total-YAP and low-level immuno-staining for phosphorylated-YAP. FGF-induced lens fibre differentiation was associated with a significant increase in cytoplasmic phosphorylated YAP (inactive state) and enhanced expression of core Hippo-signaling components. Inhibition of YAP with Verteporfin suppressed FGF-induced lens cell proliferation and ablated cell elongation during lens fibre differentiation. Inhibition of either FGFR- or MEK/ERK-signaling suppressed FGF-promoted YAP nuclear translocation. Here we propose that FGF promotes Hippo/YAP-signaling during lens cell proliferation and differentiation, with FGF-induced nuclear-YAP expression playing an essential role in promoting the proliferation of lens epithelial cells. An FGF-induced switch from proliferation to differentiation, hence regulation of lens growth, may play a key role in mediating Hippo suppression of YAP transcriptional activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Crossroads of Wnt and Hippo in epithelial tissues.

    PubMed

    Bernascone, Ilenia; Martin-Belmonte, Fernando

    2013-08-01

    Epithelial tissues undergo constant growth and differentiation during embryonic development and to replace damaged tissue in adult organs. These processes are governed by different signaling pathways that ultimately control the expression of genes associated with cell proliferation, patterning, and death. One essential pathway is Wnt, which controls tubulogenesis in several epithelial organs. Recently, Wnt has been closely linked to other signaling pathways, such as Hippo, that orchestrate proliferation and apoptosis to control organ size. There is evidence that epithelial cell junctions may sequester the transcription factors that act downstream of these signaling pathways, which would represent an important aspect of their functional regulation and their influence on cell behavior. Here, we review the transcriptional control exerted by the Wnt and Hippo signaling pathways during epithelial growth, patterning, and differentiation and recent advances in understanding of the regulation and crosstalk of these pathways in epithelial tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung

    PubMed Central

    Lange, Alexander W.; Sridharan, Anusha; Xu, Yan; Stripp, Barry R.; Perl, Anne-Karina; Whitsett, Jeffrey A.

    2015-01-01

    The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell differentiation. The transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion, consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation and inhibited differentiation of human bronchial epithelial cells in vitro. Loss of Mst1/2 and expression of YAP regulated transcriptional targets controlling cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was required for the effects of YAP on cell proliferation in vitro. Hippo/Yap signaling regulates Ajuba and controls proliferation and differentiation of lung epithelial progenitor cells. PMID:25480985

  9. Learning to Read with Augustine of Hippo

    ERIC Educational Resources Information Center

    Rine, C. Rebecca

    2007-01-01

    The confessions of Augustine of Hippo can be read as a lesson in reading, one in which Augustine teaches by example as well as precept. Throughout this work, the relationship between faith and reading is clearly on Augustine's mind, as is his desire to teach others what he has learned. As we consider our own approaches to the confluence of faith,…

  10. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control

    PubMed Central

    Zhao, Bin; Wei, Xiaomu; Li, Weiquan; Udan, Ryan S.; Yang, Qian; Kim, Joungmok; Xie, Joe; Ikenoue, Tsuneo; Yu, Jindan; Li, Li; Zheng, Pan; Ye, Keqiang; Chinnaiyan, Arul; Halder, Georg; Lai, Zhi-Chun; Guan, Kun-Liang

    2007-01-01

    The Hippo pathway plays a key role in organ size control by regulating cell proliferation and apoptosis in Drosophila. Although recent genetic studies have shown that the Hippo pathway is regulated by the NF2 and Fat tumor suppressors, the physiological regulations of this pathway are unknown. Here we show that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway. Phosphorylation by the Lats tumor suppressor kinase leads to cytoplasmic translocation and inactivation of the YAP oncoprotein. Furthermore, attenuation of this phosphorylation of YAP or Yorkie (Yki), the Drosophila homolog of YAP, potentiates their growth-promoting function in vivo. Moreover, YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition. Inhibition of YAP function restores contact inhibition in a human cancer cell line bearing deletion of Salvador (Sav), a Hippo pathway component. Interestingly, we observed that YAP protein is elevated and nuclear localized in some human liver and prostate cancers. Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact. PMID:17974916

  11. Kibra functions as a tumor suppressor protein that regulates Hippo signaling in conjunction with Merlin and Expanded

    PubMed Central

    Yu, Jianzhong; Zheng, Yonggang; Dong, Jixin; Klusza, Stephen; Deng, Wu-Min; Pan, Duojia

    2010-01-01

    Summary The Hippo signaling pathway regulates organ size and tissue homeostasis from Drosophila to mammals. Central to this pathway is a kinase cascade wherein Hippo (Hpo), in complex with Salvador (Sav), phosphorylates and activates Warts (Wts), which in turn phosphorylates and inactivates the Yorkie (Yki) oncoprotein, known as the YAP coactivator in mammalian cells. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are upstream components that regulate Hpo activity through unknown mechanisms. Here we identify Kibra (Kbr) as another upstream component of the Hippo signaling pathway. We show that Kbr functions together with Mer and Ex in a protein complex localized to the apical domain of epithelial cells, and that this protein complex regulates the Hippo kinase cascade via direct binding to Hpo and Sav. These results shed light on the mechanism of Ex and Mer function, and implicate Kbr as a potential tumor suppressor with relevance to neurofibromatosis. PMID:20159598

  12. 21 CFR 133.154 - High-moisture jack cheese.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false High-moisture jack cheese. 133.154 Section 133.154... FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.154 High-moisture jack cheese. High-moisture jack cheese conforms to...

  13. 21 CFR 133.154 - High-moisture jack cheese.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false High-moisture jack cheese. 133.154 Section 133.154... FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.154 High-moisture jack cheese. High-moisture jack cheese conforms to...

  14. Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.

    PubMed

    Lange, Alexander W; Sridharan, Anusha; Xu, Yan; Stripp, Barry R; Perl, Anne-Karina; Whitsett, Jeffrey A

    2015-02-01

    The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell differentiation. The transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion, consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation and inhibited differentiation of human bronchial epithelial cells in vitro. Loss of Mst1/2 and expression of YAP regulated transcriptional targets controlling cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was required for the effects of YAP on cell proliferation in vitro. Hippo/Yap signaling regulates Ajuba and controls proliferation and differentiation of lung epithelial progenitor cells. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  15. Reciprocal regulation of YAP/TAZ by the Hippo pathway and the Small GTPase pathway.

    PubMed

    Jang, Ju-Won; Kim, Min-Kyu; Bae, Suk-Chul

    2018-04-20

    Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively. One of the most influential aspects of YAP/TAZ biology is that these factors are transducers of cell structural features, including polarity, shape, and cytoskeletal organization. In turn, these features are intimately related to the cell's ability to attach to other cells and to the surrounding extracellular matrix (ECM), and are also influenced by the cell's microenvironment. Thus, YAP/TAZ respond to changes that occur at the level of whole tissues. Notably, small GTPases act as master organizers of the actin cytoskeleton. Recent studies provided convincing genetic evidence that small GTPase signaling pathways activate YAP/TAZ, while the Hippo pathway inhibits them. Biochemical studies showed that small GTPases facilitate the YAP-Tea domain transcription factor (TEAD) interaction by inhibiting YAP phosphorylation in response to serum stimulation, while the Hippo pathway facilitates the YAP-RUNX3 interaction by increasing YAP phosphorylation. Therefore, small GTPase pathways activate YAP/TAZ by switching its DNA-binding transcription factors. In this review, we summarize the relationship between the Hippo pathway and small GTPase pathways in the regulation of YAP/TAZ.

  16. 21 CFR 133.154 - High-moisture jack cheese.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false High-moisture jack cheese. 133.154 Section 133.154... Cheese and Related Products § 133.154 High-moisture jack cheese. High-moisture jack cheese conforms to... ingredients prescribed for monterey cheese by § 133.153, except that its moisture content is more than 44...

  17. 21 CFR 133.154 - High-moisture jack cheese.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false High-moisture jack cheese. 133.154 Section 133.154... Cheese and Related Products § 133.154 High-moisture jack cheese. High-moisture jack cheese conforms to... ingredients prescribed for monterey cheese by § 133.153, except that its moisture content is more than 44...

  18. 21 CFR 133.154 - High-moisture jack cheese.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false High-moisture jack cheese. 133.154 Section 133.154... Cheese and Related Products § 133.154 High-moisture jack cheese. High-moisture jack cheese conforms to... ingredients prescribed for monterey cheese by § 133.153, except that its moisture content is more than 44...

  19. Actin-binding and cell proliferation activities of angiomotin family members are regulated by Hippo pathway-mediated phosphorylation.

    PubMed

    Chan, Siew Wee; Lim, Chun Jye; Guo, Fusheng; Tan, Ivan; Leung, Thomas; Hong, Wanjin

    2013-12-27

    Whether the Hippo pathway has downstream targets other than YAP and TAZ is unknown. In this report, we have identified angiomotin (Amot) family members as novel substrates of Hippo core kinases. The N-terminal regions of Amot proteins contain a conserved HXRXXS consensus site for LATS1/2-mediated phosphorylation. Phospho-specific antibodies showed that Hippo core kinases could mediate phosphorylation of endogenous as well as exogenous Amot family members. Knockdown of LATS1 and LATS2 endogenously reduced the phosphorylation of Amots detected by the phospho-specific antibodies. Mutation of the serine to alanine within this HXRXXS site in Amot and AmotL2 established that this site was essential for Hippo core kinase-mediated phosphorylation. Wild-type and non-phosphorylated Amot (Amot-S175A) were targeted to actin filaments, whereas phospho-mimic Amot (Amot-S175D) failed to be localized with actin. Overexpression of LATS2 caused dissociation of Amot from actin but not Amot-S175A. Mapping of the actin-binding site of Amot showed that serine 175 of Amot was important for the actin-binding activity. Amot-S175A promoted, whereas Amot and Amot-S175D inhibited, cell proliferation. These results collectively suggest that the Hippo pathway negatively regulates the actin-binding activity of Amot family members through direct phosphorylation.

  20. 14 CFR 23.507 - Jacking loads.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Jacking loads. 23.507 Section 23.507 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... inertia forces so as to result in no change in the direction of the resultant loads at the jack points. (c...

  1. The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine.

    PubMed

    Nagashima, Shunta; Bao, Yijun; Hata, Yutaka

    2017-01-01

    Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation

    PubMed Central

    Yu, Fa-Xing; Zhang, Yifan; Park, Hyun Woo; Jewell, Jenna L.; Chen, Qian; Deng, Yaoting; Pan, Duojia; Taylor, Susan S.; Lai, Zhi-Chun; Guan, Kun-Liang

    2013-01-01

    The Hippo tumor suppressor pathway plays an important role in tissue homeostasis that ensures development of functional organs at proper size. The YAP transcription coactivator is a major effector of the Hippo pathway and is phosphorylated and inactivated by the Hippo pathway kinases Lats1/2. It has recently been shown that YAP activity is regulated by G-protein-coupled receptor signaling. Here we demonstrate that cyclic adenosine monophosphate (cAMP), a second messenger downstream from Gαs-coupled receptors, acts through protein kinase A (PKA) and Rho GTPases to stimulate Lats kinases and YAP phosphorylation. We also show that inactivation of YAP is crucial for PKA-induced adipogenesis. In addition, PKA activation in Drosophila inhibits the expression of Yorki (Yki, a YAP ortholog) target genes involved in cell proliferation and death. Taken together, our study demonstrates that Hippo–YAP is a key signaling branch of cAMP and PKA and reveals new insight into mechanisms of PKA in regulating a broad range of cellular functions. PMID:23752589

  3. The centrosomal component CEP161 of Dictyostelium discoideum interacts with the Hippo signaling pathway

    PubMed Central

    Sukumaran, Salil K.; Blau-Wasser, Rosemarie; Rohlfs, Meino; Gallinger, Christoph; Schleicher, Michael; Noegel, Angelika A

    2015-01-01

    CEP161 is a novel component of the Dictyostelium discoideum centrosome which was identified as binding partner of the pericentriolar component CP250. Here we show that the amino acids 1-763 of the 1381 amino acids CEP161 are sufficient for CP250 binding, centrosomal targeting and centrosome association. Analysis of AX2 cells over-expressing truncated and full length CEP161 proteins revealed defects in growth and development. By immunoprecipitation experiments we identified the Hippo related kinase SvkA (Hrk-svk) as binding partner for CEP161. Both proteins colocalize at the centrosome. In in vitro kinase assays the N-terminal domain of CEP161 (residues 1-763) inhibited the kinase activity of Hrk-svk. A comparison of D. discoideum Hippo kinase mutants with mutants overexpressing CEP161 polypeptides revealed similar defects. We propose that the centrosomal component CEP161 is a novel player in the Hippo signaling pathway and affects various cellular properties through this interaction. PMID:25607232

  4. Estrogen regulates Hippo signaling via GPER in breast cancer

    PubMed Central

    Zhou, Xin; Wang, Shuyang; Wang, Zhen; Feng, Xu; Liu, Peng; Lv, Xian-Bo; Li, Fulong; Yu, Fa-Xing; Sun, Yiping; Yuan, Haixin; Zhu, Hongguang; Xiong, Yue; Lei, Qun-Ying; Guan, Kun-Liang

    2015-01-01

    The G protein–coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis. PMID:25893606

  5. Estrogen regulates Hippo signaling via GPER in breast cancer.

    PubMed

    Zhou, Xin; Wang, Shuyang; Wang, Zhen; Feng, Xu; Liu, Peng; Lv, Xian-Bo; Li, Fulong; Yu, Fa-Xing; Sun, Yiping; Yuan, Haixin; Zhu, Hongguang; Xiong, Yue; Lei, Qun-Ying; Guan, Kun-Liang

    2015-05-01

    The G protein-coupled estrogen receptor (GPER) mediates both the genomic and nongenomic effects of estrogen and has been implicated in breast cancer development. Here, we compared GPER expression in cancerous tissue and adjacent normal tissue in patients with invasive ductal carcinoma (IDC) of the breast and determined that GPER is highly upregulated in cancerous cells. Additionally, our studies revealed that GPER stimulation activates yes-associated protein 1 (YAP) and transcriptional coactivator with a PDZ-binding domain (TAZ), 2 homologous transcription coactivators and key effectors of the Hippo tumor suppressor pathway, via the Gαq-11, PLCβ/PKC, and Rho/ROCK signaling pathways. TAZ was required for GPER-induced gene transcription, breast cancer cell proliferation and migration, and tumor growth. Moreover, TAZ expression positively correlated with GPER expression in human IDC specimens. Together, our results suggest that the Hippo/YAP/TAZ pathway is a key downstream signaling branch of GPER and plays a critical role in breast tumorigenesis.

  6. A note on the Goodman Jack

    USGS Publications Warehouse

    Swolfs, H.S.; Kibler, J.D.

    1982-01-01

    A Note on the Goodman Jack: Reconnaissance experiments, performed to evaluate the practical utility of the hard-rock variety of the Goodman Jack, reveal that the Hustrulid-T* correction adequately reconciles the discrepancy between the measured and true deformation modulus of the rock mass in the range of 30 to 50 gigapascals. ?? 1982 Springer-Verlag.

  7. LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.

    PubMed

    Tanaka, I; Osada, H; Fujii, M; Fukatsu, A; Hida, T; Horio, Y; Kondo, Y; Sato, A; Hasegawa, Y; Tsujimura, T; Sekido, Y

    2015-01-02

    Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation.

  8. Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration

    PubMed Central

    Lu, Li; Finegold, Milton J; Johnson, Randy L

    2018-01-01

    The mammalian liver has a remarkable capacity for repair following injury. Removal of up to two-third of liver mass results in a series of events that include extracellular matrix remodeling, coordinated hepatic cell cycle re-entry, restoration of liver mass and tissue remodeling to return the damaged liver to its normal state. Although there has been considerable advancement of our knowledge concerning the regenerative capacity of the mammalian liver, many outstanding questions remaining, such as: how does the regenerating liver stop proliferating when appropriate mass is restored and how do these mechanisms relate to normal regulation of organ size during development? Hippo pathway has been proposed to be central in mediating both events: organ size control during development and following regeneration. In this report, we examined the role of Yap and Taz, key components of the Hippo pathway in liver organ size regulation, both in the context of development and homeostasis. Our studies reveal that contrary to the current paradigms that Yap/Taz are not required for developmental regulation of liver size but are required for proper liver regeneration. In livers depleted of Yap and Taz, liver mass is elevated in neonates and adults. However, Yap/Taz-depleted livers exhibit profound defects in liver regeneration, including an inability to restore liver mass and to properly coordinate cell cycle entry. Taken together, our results highlight requirements for the Hippo pathway during liver regeneration and indicate that there are additional pathways that cooperate with Hippo signaling to control liver size during development and in the adult. PMID:29303509

  9. [Effects of Hippo signaling on anti-oxidative stress of mesenchymal stem cells in vitro].

    PubMed

    Li, Lang; Dong, Liang; Hui, Jiaojie; Gao, Fei; Wang, Qiuhui; Yang, Lan; Zhang, Jiangqian; Yan, Jie

    2018-04-01

    To explore the effects of Hippo signaling on anti-oxidative stress of mouse marrow mesenchymal stem cells (mMSCs) in vitro. mMSCs derived from C57BL/6 mice were identified using fluorescence-activated cell sorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. 2-deoxy-D-glucose (2-DG) or XMU-MP-1 was used to modulate Hippo signaling. Oxidative stress was induced by H 2 O 2 treatment and the effect of oxidative stress induced by H 2 O 2 on survival of mMSCs was evaluated using methyl thiazolyl tetrazolium (MTT) assay. The effect of oxidative stress induced by H 2 O 2 on Hippo signaling and the effect of Hippo signaling on capability of anti-oxidative stress of mMSCs were analyzed through apoptosis-regulated proteins (Bcl-2 and Bax) using Western Blot. Hippo signaling was activated by 2-DG in a concentration-dependent manner and the effect was most prominent by 5 mmol/L of 2-DG [compared with the blank control group, large tumor suppressor 1 (LATS1) protein (grey value): 2.33±0.25 vs. 0.98±0.03, phosphorylated Yes-associated protein (p-YAP)/YAP protein ratio (grey value): 2.30±0.35 vs. 1.01±0.05, 14-3-3 protein (grey value): 2.19±0.40 vs. 0.99±0.04, all P < 0.05]; Hippo signaling was inhibited by 100 nmol/L of XMU-MP-1 [compared with the blank control group, LATS1 protein (grey value): 0.69±0.10 vs. 0.98±0.03, p-YAP/YAP protein ratio (grey value): 0.65±0.06 vs. 1.01±0.05, 14-3-3 protein (grey value): 0.75±0.11 vs. 0.99±0.04, all P < 0.05]. Death of mMSCs was induced by H 2 O 2 in a concentration-dependent manner and the minimal effective concentration was 0.1 mmol/L [compared with the blank control group, survival rate of mMSCs: (81.25±11.85)% vs. (100.44±12.39)%, P < 0.05]. Inhibition of Hippo signaling was induced by H 2 O 2 in a concentration-dependent manner and the minimal effective concentration was also 0.1 mmol/L [compared with the blank control group, LATS1 protein (grey value): 0.75±0

  10. Extent and Effectiveness of Coral Reef Marine Protected Areas for a Ubiquitous Mesopredator, Bluefin Trevally (Caranx melampygus)

    NASA Astrophysics Data System (ADS)

    Del Raye, G.; Weng, K.

    2012-12-01

    An urgent challenge facing global marine fisheries is the zoning and implementation of marine protected areas (MPAs). Effective zoning of MPAs requires detailed knowledge of the movement patterns and habitat usage of the species to be protected, yet this information is deficient for many coral reef fishes. We use new detailed acoustic tracking and habitat usage data for a ubiquitous coral reef predator - Caranx melampygus - to understand how well existing MPAs protect this highly fished stock. Surprisingly, our data show that as little as 12% of the MPAs existing within the distribution of C. melampygus are large enough to encompass the movement range of even a single adult individual, suggesting that the establishment of larger coral reef MPAs will be crucial for the sustainable harvesting of this species. These results underscore the urgency of obtaining tracking data for other important coral reef species to better understand the impact of current and planned MPAs on their fisheries.

  11. Comparison of upper tropospheric carbon monoxide from MOPITT, ACE-FTS, and HIPPO-QCLS

    NASA Astrophysics Data System (ADS)

    Martínez-Alonso, Sara; Deeter, Merritt N.; Worden, Helen M.; Gille, John C.; Emmons, Louisa K.; Pan, Laura L.; Park, Mijeong; Manney, Gloria L.; Bernath, Peter F.; Boone, Chris D.; Walker, Kaley A.; Kolonjari, Felicia; Wofsy, Steven C.; Pittman, Jasna; Daube, Bruce C.

    2014-12-01

    Products from the Measurements Of Pollution In The Troposphere (MOPITT) instrument are regularly validated using in situ airborne measurements. However, few of these measurements reach into the upper troposphere, thus hindering MOPITT validation in that region. Here we evaluate upper tropospheric (~500 hPa to the tropopause) MOPITT CO profiles by comparing them to satellite Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) retrievals and to measurements from the High-performance Instrumented Airborne Platform for Environmental Research Pole to Pole Observations (HIPPO) Quantum Cascade Laser Spectrometer (QCLS). Direct comparison of colocated v5 MOPITT thermal infrared-only retrievals, v3.0 ACE-FTS retrievals, and HIPPO-QCLS measurements shows a slight positive MOPITT CO bias within its 10% accuracy requirement with respect to the other two data sets. Direct comparison of colocated ACE-FTS and HIPPO-QCLS measurements results in a small number of samples due to the large disparity in sampling pattern and density of these data sets. Thus, two additional indirect techniques for comparison of noncoincident data sets have been applied: tracer-tracer (CO-O3) correlation analysis and analysis of profiles in tropopause coordinates. These techniques suggest a negative bias of ACE-FTS with respect to HIPPO-QCLS; this could be caused by differences in resolution (horizontal, vertical) or by deficiencies in the ACE-FTS CO retrievals below ~20 km of altitude, among others. We also investigate the temporal stability of MOPITT and ACE-FTS data, which provide unique global CO records and are thus important in climate analysis. Our results indicate that the relative bias between the two data sets has remained generally stable during the 2004-2010 period.

  12. AmeriFlux CA-SJ3 Saskatchewan - Western Boreal, Jack Pine forest harvested in 1975 (BOREAS Young Jack Pine)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barr, Alan

    This is the AmeriFlux version of the carbon flux data for the site CA-SJ3 Saskatchewan - Western Boreal, Jack Pine forest harvested in 1975 (BOREAS Young Jack Pine). Site Description - 53.87581° N, 104.64529° W, BOREAS 1994, 1996, BERMS climate and flux measurements to begin Spring 2003

  13. Hippo/crates-in-situ deformation strain and testure studies using neutron time-of-flight diffraction.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vogel, S. C.; Hartig, C.; Brissier, T. D.

    2005-01-01

    In situ deformation studies by diffraction allow studying of deformation mechanisms and provide valuable data to validate and improve deformation models. In particular, deformation studies using time-of-flight neutrons provide averages over large numbers of grains and allow to probing the response of lattice planes parallel and perpendicular to the applied load simultaneously. In this paper we describe the load-frame CRATES, designed for the HIPPO neutron time-of-flight diffractometer at LANSCE. The HIPPO/CRATES combination allows probing up to 20 diffraction vectors simultaneously and provides rotation of the sample in the beam while under load. With this, deformation texture, i.e. the change ofmore » grain orientation due to plastic deformation, or strain pole figures may be measured. We report initial results of a validation experiment, comparing deformation of a Zircaloy specimen measured using the NPD neutron diffractometer with results obtained for the same material using HIPPO/CRATES.« less

  14. The Hippo signaling pathway: a potential therapeutic target is reversed by a Chinese patent drug in rats with diabetic retinopathy.

    PubMed

    Hao, Gai-Mei; Lv, Tian-Tian; Wu, Yan; Wang, Hong-Liang; Xing, Wei; Wang, Yong; Li, Chun; Zhang, Zi-Jian; Wang, Zheng-Lin; Wang, Wei; Han, Jing

    2017-04-04

    The Hippo signaling pathway is reported to be involved in angiogenesis, but the roles of the Hippo pathway in diabetic retinopathy have not been addressed. Fufang Xueshuantong Capsule has been used to treat diabetic retinopathy in China; however, the effect of Fufang Xueshuantong Capsule on the Hippo pathway has not been investigated. In this study, diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Twenty weeks later, Fufang Xueshuantong Capsule was administered for 12 weeks. When the administration ended, the eyes were isolated for western blot and immunohistochemistry analyses. The levels of P- mammalian sterile 20-like (MST), large tumor suppressor homolog (Lats), P- yes-associated protein (YAP), transcriptional co-activator with PDZ binding motif (TAZ) and TEA domain family members (TEAD) were measured. Diabetic rats had a decreased P-MST level in the inner plexiform layer and reduced expression of P-YAP in the photoreceptor layers of their eyes. In addition, diabetic rats displayed remarkable increases in Lats, TAZ and TEAD in their retinas. Furthermore, Fufang Xueshuantong Capsule restored the changes in the Hippo pathway. The Hippo signaling pathway is important for the progression of diabetic retinopathy and will hopefully be a targeted therapeutic approach for the prevention of diabetic retinopathy.

  15. Ski regulates Hippo and TAZ signaling to suppress breast cancer progression

    PubMed Central

    Rashidian, Juliet; Le Scolan, Erwan; Ji, Xiaodan; Zhu, Qingwei; Mulvihill, Melinda M.; Nomura, Daniel; Luo, Kunxin

    2015-01-01

    Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor–β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and subsequent degradation of TAZ. Ski also promoted the degradation of a constitutively active TAZ mutant that is not phosphorylated by Lats, suggesting the existence of a Lats2-independent degradation pathway. Finally, we showed that Ski repressed the transcriptional activity of TAZ by binding to the TAZ partner TEAD and recruiting the transcriptional co-repressor NCoR1 to the TEAD-TAZ complex. Ski effectively reversed transformation and epithelial-to-mesenchyme transition in cultured breast cancer cells and metastasis in TAZ-expressing xenografted tumors. Thus, Ski inhibited the function of TAZ through multiple mechanisms in human cancer cells. PMID:25670202

  16. The Hippo Signaling Pathway Regulates Ovarian Function via the Proliferation of Ovarian Germline Stem Cells.

    PubMed

    Ye, Haifeng; Li, Xiaoyan; Zheng, Tuochen; Hu, Chuan; Pan, Zezheng; Huang, Jian; Li, Jia; Li, Wei; Zheng, Yuehui

    2017-01-01

    To improve the separation, identification and cultivation of ovarian germline stem cells (OGSCs), to clarify the relationship between the Hippo signaling pathway effector YAP1 and the proliferation and differentiation of OGSCs in vitro and to identify the major contribution of Hippo signaling to ovarian function. Two-step enzymatic separation processes and magnetic separation were used to isolate and identify OGSCs by determining the expression of Mvh, Oct4, Nanog, Fragilis and Stella markers. Then, YAP1, as the main effector molecule in the Hippo signaling pathway, was chosen as the target gene of the study. Lentivirus containing overexpressed YAP1 or a YAP1-targeted shRNA was transduced into OGSCs. The effects of modulating the Hippo signaling pathway on the proliferation, differentiation, reproduction and endocrine function of ovaries were observed by microinjecting the lentiviral vectors with overexpressed YAP1 or YAP1 shRNA into infertile mouse models or natural mice of reproductive age. (1) The specific expression of Mvh, Oct4, Nanog, Fragilis and Stella markers was observed in isolated stem cells. Thus, the isolated cells were preliminarily identified as OGSCs. (2) The co-expression of LATS2, MST1, YAP1 and MVH was observed in isolated OGSCs. Mvh and Oct4 expression levels were significantly increased in OGSCs overexpressing YAP1 compared to GFP controls. Consistently, Mvh and Oct4 levels were significantly decreased in cells expressing YAP1-targeted shRNA. (3) After 14-75 days of YAP1 overexpression in infertile mouse models, we detected follicle regeneration in ovaries, the activation of primordial follicles and increased birth rate, accompanied by increasing levels of E2 and FSH. (4) However, we detected decreasing follicles in ovaries, lower birth rate, and decreasing E2 and FSH in serum from healthy mice of reproductive age following YAP1 shRNA expression. Methods for the isolation, identification and culture of OGSCs were successfully established

  17. MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway.

    PubMed

    Alam, Maroof; Bouillez, Audrey; Tagde, Ashujit; Ahmad, Rehan; Rajabi, Hasan; Maeda, Takahiro; Hiraki, Masayuki; Suzuki, Yozo; Kufe, Donald

    2016-12-01

    Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C--terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known whether MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation, and apoptosis. Also shown is that MUC1-C--mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes, and induces the WNT target gene MYC. These data support a previously unrecognized pathway in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin-mediated induction of MYC expression. These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. Mol Cancer Res; 14(12); 1266-76. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. MUC1-C Represses the Crumbs Complex Polarity Factor CRB3 and Downregulates the Hippo Pathway

    PubMed Central

    Alam, Maroof; Bouillez, Audrey; Tagde, Ashujit; Ahmad, Rehan; Rajabi, Hasan; Maeda, Takahiro; Hiraki, Masayuki; Suzuki, Yozo; Kufe, Donald

    2016-01-01

    Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C-terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known if MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells. MUC1-C associates with ZEB1 on the CRB3 promoter and represses CRB3 transcription. Notably, CRB3 activates the core kinase cassette of the Hippo pathway, which includes LATS1 and LATS2. In this context, targeting MUC1-C was associated with increased phosphorylation of LATS1, consistent with activation of the Hippo pathway, which is critical for regulating cell contact, tissue repair, proliferation and apoptosis. Also shown is that MUC1-C-mediated suppression of CRB3 and the Hippo pathway is associated with dephosphorylation and activation of the oncogenic YAP protein. In turn, MUC1-C interacts with YAP, promotes formation of YAP/β-catenin complexes and induces the WNT target gene MYC. These data support a previously unrecognized model in which targeting MUC1-C in TNBC cells (i) induces CRB3 expression, (ii) activates the CRB3-driven Hippo pathway, (iii) inactivates YAP, and thereby (iv) suppresses YAP/β-catenin-mediated induction of MYC expression. Implications These findings demonstrate a previously unrecognized role for the MUC1-C oncoprotein in the regulation of polarity and the Hippo pathway in breast cancer. PMID:27658423

  19. Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice

    PubMed Central

    Morikawa, Yuka; Zhang, Min; Heallen, Todd; Leach, John; Tao, Ge; Xiao, Yang; Bai, Yan; Li, Wei; Willerson, James T.; Martin, James F.

    2015-01-01

    The mammalian heart regenerates poorly, and damage commonly leads to heart failure. Hippo signaling is an evolutionarily conserved kinase cascade that regulates organ size during development and prevents adult mammalian cardiomyocyte regeneration by inhibiting the transcriptional coactivator Yap, which also responds to mechanical signaling in cultured cells to promote cell proliferation. To identify Yap target genes that are activated during cardiomyocyte renewal and regeneration, we performed Yap chromatin immunoprecipitation sequencing (ChIP-Seq) and mRNA expression profiling in Hippo signaling-deficient mouse hearts. We found that Yap directly regulated genes encoding cell cycle progression proteins, as well as genes encoding proteins that promote F-actin polymerization and that link the actin cytoskeleton to the extracellular matrix. Included in the latter group were components of the dystrophin glycoprotein complex (DGC), a large molecular complex that, when defective, results in muscular dystrophy in humans. Cardiomyocytes near scar tissue of injured Hippo signaling-deficient mouse hearts showed cellular protrusions suggestive of cytoskeletal remodeling. The hearts of mdx mutant mice, which lack functional dystrophin and are a model for muscular dystrophy, showed impaired regeneration and cytoskeleton remodeling, but normal cardiomyocyte proliferation after injury. Our data showed that, in addition to genes encoding cell cycle progression proteins, Yap regulated genes that enhance cytoskeletal remodeling Thus, blocking the Hippo pathway input to Yap may tip the balance so that Yap responds to the mechanical changes associated with heart injury to promote repair. PMID:25943351

  20. AmeriFlux US-NMj Northern Michigan Jack Pine Stand

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Jiquan

    This is the AmeriFlux version of the carbon flux data for the site US-NMj Northern Michigan Jack Pine Stand. Site Description - The jack pine site is owned by Michigan Technological University. The stand is managed, and thus thinned and harvested depending on stand age. This jack pine site is naturally regenerating following a clearcut around 1989. Heavy snow in December 2001 c

  1. Advanced jack up rig breaking U.S. construction drought

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kelly, P.

    1997-03-10

    A new heavy duty jack up, due in mid-1998, will be able to simultaneously drill and produce wells in harsher environments and deeper water than current jack ups in the worldwide fleet. Rowan Cos. Inc.`s Gorilla V is the only mobile offshore drilling unit (MODU) currently under construction in the US. Two more enhanced Gorilla design rigs are planned before the year 2000. The enhanced Gorilla class jack up represents the most technologically advanced jack up unit constructed to date. The rigs are structurally designed to meet year-round weather challenges in the harshest geographical environments. Rising demand for drilling rigs,more » coupled with a dwindling fleet, is generating supply shortages around the world, particularly at the high-specification end of the market. Even increasing the historical retirement age from 20 to 25 years, rig attrition continues at a level of about 18 rigs per year. Apart from the jack up market per se, however, Rowan`s strategy in designing and building enhanced Gorillas is to improve existing jack up drilling technology and offer the versatility to operate as a drilling unit, a mobile production unit, or both simultaneously in either open water locations or alongside existing platforms. The paper discusses the market for these heavy jack-ups, the use of one on the Cohasset project in Nova Scotia, the Gorilla V and enhanced Gorillas, geographical range of use, and MOPU economics.« less

  2. Jack Hills, Australia

    NASA Image and Video Library

    2009-06-02

    This image acquired by NASA Terra spacecraft, shows the oldest material on Earth which has yet been dated by man is a zircon mineral of 4.4 billion years old from a sedimentary gneiss in the Jack Hills of the Narre Gneiss Terrane of Australia.

  3. Transcriptional regulators in the Hippo signaling pathway control organ growth in Xenopus tadpole tail regeneration.

    PubMed

    Hayashi, Shinichi; Ochi, Haruki; Ogino, Hajime; Kawasumi, Aiko; Kamei, Yasuhiro; Tamura, Koji; Yokoyama, Hitoshi

    2014-12-01

    The size and shape of tissues are tightly controlled by synchronized processes among cells and tissues to produce an integrated organ. The Hippo signaling pathway controls both cell proliferation and apoptosis by dual signal-transduction states regulated through a repressive kinase cascade. Yap1 and Tead, transcriptional regulators that act downstream of the Hippo signaling kinase cascade, have essential roles in regulating cell proliferation. In amphibian limb or tail regeneration, the local tissue outgrowth terminates when the correct size is reached, suggesting that organ size is strictly controlled during epimorphic organ-level regeneration. We recently demonstrated that Yap1 is required for the regeneration of Xenopus tadpole limb buds (Hayashi et al., 2014, Dev. Biol. 388, 57-67), but the molecular link between the Hippo pathway and organ size control in vertebrate epimorphic regeneration is not fully understood. To examine the requirement of Hippo pathway transcriptional regulators in epimorphic regeneration, including organ size control, we inhibited these regulators during Xenopus tadpole tail regeneration by overexpressing a dominant-negative form of Yap (dnYap) or Tead4 (dnTead4) under a heat-shock promoter in transgenic animal lines. Each inhibition resulted in regeneration defects accompanied by reduced cell mitosis and increased apoptosis. Single-cell gene manipulation experiments indicated that Tead4 cell-autonomously regulates the survival of neural progenitor cells in the regenerating tail. In amphibians, amputation at the proximal level of the tail (deep amputation) results in faster regeneration than that at the distal level (shallow amputation), to restore the original-sized tail with similar timing. However, dnTead4 overexpression abolished the position-dependent differential growth rate of tail regeneration. These results suggest that the transcriptional regulators in the Hippo pathway, Tead4 and Yap1, are required for general vertebrate

  4. Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling

    PubMed Central

    2011-01-01

    Background Epithelial neoplasias are associated with alterations in cell polarity and excessive cell proliferation, yet how these neoplastic properties are related to one another is still poorly understood. The study of Drosophila genes that function as neoplastic tumor suppressors by regulating both of these properties has significant potential to clarify this relationship. Results Here we show in Drosophila that loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling in the epithelial tissues of both the eye and wing imaginal disc. scrib mutant tissue overgrowth, but not the loss of cell polarity, is dependent upon defective Hippo signaling and can be rescued by knockdown of either the TEAD/TEF family transcription factor Scalloped or the transcriptional coactivator Yorkie in the eye disc, or reducing levels of Yorkie in the wing disc. Furthermore, loss of Scrib sensitizes tissue to transformation by oncogenic Ras-Raf signaling, and Yorkie-Scalloped activity is required to promote this cooperative tumor overgrowth. The inhibition of Hippo signaling in scrib mutant eye disc clones is not dependent upon JNK activity, but can be significantly rescued by reducing aPKC kinase activity, and ectopic aPKC activity is sufficient to impair Hippo signaling in the eye disc, even when JNK signaling is blocked. In contrast, warts mutant overgrowth does not require aPKC activity. Moreover, reducing endogenous levels of aPKC or increasing Scrib or Lethal giant larvae levels does not promote increased Hippo signaling, suggesting that aPKC activity is not normally rate limiting for Hippo pathway activity. Epistasis experiments suggest that Hippo pathway inhibition in scrib mutants occurs, at least in part, downstream or in parallel to both the Expanded and Fat arms of Hippo pathway regulation. Conclusions Loss of Scrib promotes Yorkie/Scalloped-dependent epithelial tissue overgrowth, and this is also

  5. DLG5 connects cell polarity and Hippo signaling protein networks by linking PAR-1 with MST1/2

    PubMed Central

    Kwan, Julian; Sczaniecka, Anna; Heidary Arash, Emad; Nguyen, Liem; Chen, Chia-Chun; Ratkovic, Srdjana; Klezovitch, Olga; Attisano, Liliana; McNeill, Helen; Emili, Andrew; Vasioukhin, Valeri

    2016-01-01

    Disruption of apical–basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation. Affinity purification/mass spectrometry revealed a critical role of DLG5 in the formation of protein assemblies containing core Hippo kinases mammalian ste20 homologs 1/2 (MST1/2) and Par-1 polarity proteins microtubule affinity-regulating kinases 1/2/3 (MARK1/2/3). Consistent with this finding, Hippo signaling is markedly hyperactive in mammalian Dlg5−/− tissues and cells in vivo and ex vivo and in Drosophila upon dlg5 knockdown. Conditional deletion of Mst1/2 fully rescued the phenotypes of brain-specific Dlg5 knockout mice. Dlg5 also interacts genetically with Hippo effectors Yap1/Taz. Mechanistically, we show that DLG5 inhibits the association between MST1/2 and large tumor suppressor homologs 1/2 (LATS1/2), uses its scaffolding function to link MST1/2 with MARK3, and inhibits MST1/2 kinase activity. These data reveal a direct connection between cell polarity proteins and Hippo, which is essential for proper development of multicellular organisms. PMID:28087714

  6. Jack Pine

    Treesearch

    William Dent Sterrett

    1920-01-01

    Jack pine is a very frugal tree in its climatic and soil requirements. The northern limit of its natural range is within 14 degrees of the Arctic Circle and the southern is marked by the southern shores of Lake Michigan. No other North American pine grows naturally so far north and all the others grow farther south. It develops commercial stands and reproduces itself...

  7. Zyxin-Siah2–Lats2 axis mediates cooperation between Hippo and TGF-β signalling pathways

    PubMed Central

    Ma, Biao; Cheng, Hongcheng; Gao, Ruize; Mu, Chenglong; Chen, Ling; Wu, Shian; Chen, Quan; Zhu, Yushan

    2016-01-01

    The evolutionarily conserved Hippo pathway is a regulator that controls organ size, cell growth and tissue homeostasis. Upstream signals of the Hippo pathway have been widely studied, but how microenvironmental factors coordinately regulate this pathway remains unclear. In this study, we identify LIM domain protein Zyxin, as a scaffold protein, that in response to hypoxia and TGF-β stimuli, forms a ternary complex with Lats2 and Siah2 and stabilizes their interaction. This interaction facilitates Lats2 ubiquitination and degradation, Yap dephosphorylation and subsequently activation. We show that Zyxin is required for TGF-β and hypoxia-induced Lats2 downregulation and deactivation of Hippo signalling in MDA-MB-231 cells. Depletion of Zyxin impairs the capability of cell migration, proliferation and tumourigenesis in a xenograft model. Zyxin is upregulated in human breast cancer and positively correlates with histological stages and metastasis. Our study demonstrates that Zyxin-Lats2–Siah2 axis may serve as a potential therapeutic target in cancer treatment. PMID:27030211

  8. JACK - ANTHROPOMETRIC MODELING SYSTEM FOR SILICON GRAPHICS WORKSTATIONS

    NASA Technical Reports Server (NTRS)

    Smith, B.

    1994-01-01

    JACK is an interactive graphics program developed at the University of Pennsylvania that displays and manipulates articulated geometric figures. JACK is typically used to observe how a human mannequin interacts with its environment and what effects body types will have upon the performance of a task in a simulated environment. Any environment can be created, and any number of mannequins can be placed anywhere in that environment. JACK includes facilities to construct limited geometric objects, position figures, perform a variety of analyses on the figures, describe the motion of the figures and specify lighting and surface property information for rendering high quality images. JACK is supplied with a variety of body types pre-defined and known to the system. There are both male and female bodies, ranging from the 5th to the 95th percentile, based on NASA Standard 3000. Each mannequin is fully articulated and reflects the joint limitations of a normal human. JACK is an editor for manipulating previously defined objects known as "Peabody" objects. Used to describe the figures as well as the internal data structure for representing them, Peabody is a language with a powerful and flexible mechanism for representing connectivity between objects, both the joints between individual segments within a figure and arbitrary connections between different figures. Peabody objects are generally comprised of several individual figures, each one a collection of segments. Each segment has a geometry represented by PSURF files that consist of polygons or curved surface patches. Although JACK does not have the capability to create new objects, objects may be created by other geometric modeling programs and then translated into the PSURF format. Environment files are a collection of figures and attributes that may be dynamically moved under the control of an animation file. The animation facilities allow the user to create a sequence of commands that duplicate the movements of a

  9. Validation of OCO-2 and ACOS-GOSAT using HIPPO and TCCON

    NASA Technical Reports Server (NTRS)

    Kulawik, Susan S.; Wunch, Debra; O'Dell, Christopher; Miller, Charles; Osterman, Greg; Wennberg, Paul; Griffith, David; Sherlock, Vanessa; Deutscher, Nicholas M.; Notholt, Justus; hide

    2017-01-01

    Consistent validation of satellite CO2 estimates is a prerequisite for using multiple satellite CO2measurements for joint flux inversion and establishing a long-term atmospheric CO2 data record. Wevalidate recent satellite observation of OCO-2 v7 and ACOS-GOSAT v7.3 using similar analysis as previouswork (Kulawik et al. (2016) and Frankenberg et al. (2106)) through comparisons to the HIAPER Pole-to-Pole Observations (HIPPO) and the Total Carbon Column Observing Network (TCCON) to estimate biasesand errors affecting the understanding of carbon cycle science. CarbonTracker RT is also compared tothe validation data, and additionally used to evaluate the mismatch between the HIPPO observationtimeframe and the OCO-2 record, which are offset by 3-7 years. Some key metrics that are validatedinclude the seasonal cycle phase and amplitude, latitudinal gradient by season, regional biases, anderrors with respect to averaging.

  10. The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma.

    PubMed

    Kong, Fei; Li, Yunguang; Hu, Enze; Wang, Rui; Wang, Junhao; Liu, Jin; Zhang, Jinsan; He, Dacheng; Xiao, Xueyuan

    2016-01-01

    S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC.

  11. MiR-93-5p promotes gastric cancer-cell progression via inactivation of the Hippo signaling pathway.

    PubMed

    Li, Li; Zhao, Jianguo; Huang, Shanshan; Wang, Yi; Zhu, Lingling; Cao, Yuan; Xiong, Jianping; Deng, Jun

    2018-01-30

    MiR-93-5p has been previously found to be associated with gastric cancer (GC) tumorigenesis; however, the current understanding of its function in this context remains largely incomplete. In the present study, we showed that miR-93-5p was upregulated in GC tissues. We also demonstrated that miR-93-5p overexpression promoted the proliferation, migration, invasion, and chemoresistance of SGC-7901 cells in vitro, and conversely, that endogenously silencing miR-93-5p expression induced the opposite effects in HGC-27 cells. Overexpression of miR-93-5p was found to inactivate the Hippo pathway, and furthermore, miR-93-5p knockdown activated Hippo signaling. MiR-93-5p upregulation was also shown to inhibit the expression of two well-characterized Hippo pathway regulators, protocadherin Fat 4 (FAT4), and large tumor suppressors 2 (LATS2), at both the mRNA and protein level. Additionally, the results of bioinformatics analyses and luciferase reporter assays indicated that miR-93-5p directly targets the 3'-UTR of FAT4 and LATS2. Taken together, these results demonstrate that miR-93-5p promotes GC-cell progression via the inactivation of the Hippo signaling pathway, and thus, represents a potential therapeutic target for the treatment of GC. Copyright © 2017. Published by Elsevier B.V.

  12. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression

    PubMed Central

    He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

    2015-01-01

    The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. PMID:26417066

  13. AmeriFlux US-Wi9 Young Jack pine (YJP)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Jiquan

    This is the AmeriFlux version of the carbon flux data for the site US-Wi9 Young Jack pine (YJP). Site Description - The Wisconsin Young Jack Pine site is located in the Washburn Ranger District of the northeastern section of Chequamegon National Forest. A member of the northern coniferous-deciduous biome, surveys from the mid-19th century indicate the region consisted of a mixed stand of red, white, and jack pines. After extensive timber harvesting, wildfires, and farming activity, the region turned into a fragmented mosaic of stands of various ages and composition. As an assemblage, the ten Wisconsin sites are indicative ofmore » the successional stages of development in the predominant stand types of a physically homogeneous landscape. Clearcut on 40 to 70 year intervals, jack pine stands occupy approximately 13% of the region.« less

  14. Par-aPKC-dependent and -independent mechanisms cooperatively control cell polarity, Hippo signaling, and cell positioning in 16-cell stage mouse embryos.

    PubMed

    Hirate, Yoshikazu; Hirahara, Shino; Inoue, Ken-Ichi; Kiyonari, Hiroshi; Niwa, Hiroshi; Sasaki, Hiroshi

    2015-10-01

    In preimplantation mouse embryos, the Hippo signaling pathway plays a central role in regulating the fates of the trophectoderm (TE) and the inner cell mass (ICM). In early blastocysts with more than 32 cells, the Par-aPKC system controls polarization of the outer cells along the apicobasal axis, and cell polarity suppresses Hippo signaling. Inactivation of Hippo signaling promotes nuclear accumulation of a coactivator protein, Yap, leading to induction of TE-specific genes. However, whether similar mechanisms operate at earlier stages is not known. Here, we show that slightly different mechanisms operate in 16-cell stage embryos. Similar to 32-cell stage embryos, disruption of the Par-aPKC system activated Hippo signaling and suppressed nuclear Yap and Cdx2 expression in the outer cells. However, unlike 32-cell stage embryos, 16-cell stage embryos with a disrupted Par-aPKC system maintained apical localization of phosphorylated Ezrin/Radixin/Moesin (p-ERM), and the effects on Yap and Cdx2 were weak. Furthermore, normal 16-cell stage embryos often contained apolar cells in the outer position. In these cells, the Hippo pathway was strongly activated and Yap was excluded from the nuclei, thus resembling inner cells. Dissociated blastomeres of 8-cell stage embryos form polar-apolar couplets, which exhibit different levels of nuclear Yap, and the polar cell engulfed the apolar cell. These results suggest that cell polarization at the 16-cell stage is regulated by both Par-aPKC-dependent and -independent mechanisms. Asymmetric cell division is involved in cell polarity control, and cell polarity regulates cell positioning and most likely controls Hippo signaling. © The Authors Development, Growth & Differentiation published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Society of Developmental Biologists.

  15. Texture and phase analysis of deformed SUS304 by using HIPPO

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Takajo, Shigehiro; Vogel, Sven C.

    2016-11-15

    These slides represent the author's research activity at Los Alamos National Laboratory (LANL), which is about texture and phase analysis of deformed SUS304 by using HIPPO. The following topics are covered: diffraction histogram at each sample position, diffraction histogram (all bank data averaged), possiblity of ε-phase, MAUD analysis with including ε-phase.

  16. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression.

    PubMed

    He, Chunbo; Mao, Dagan; Hua, Guohua; Lv, Xiangmin; Chen, Xingcheng; Angeletti, Peter C; Dong, Jixin; Remmenga, Steven W; Rodabaugh, Kerry J; Zhou, Jin; Lambert, Paul F; Yang, Peixin; Davis, John S; Wang, Cheng

    2015-11-01

    The Hippo signaling pathway controls organ size and tumorigenesis through a kinase cascade that inactivates Yes-associated protein (YAP). Here, we show that YAP plays a central role in controlling the progression of cervical cancer. Our results suggest that YAP expression is associated with a poor prognosis for cervical cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo signaling pathway and activate YAP to induce cervical cancer cell proliferation and migration. Activated YAP allows for up-regulation of TGF-α, AREG, and EGFR, forming a positive signaling loop to drive cervical cancer cell proliferation. HPV E6 protein, a major etiological molecule of cervical cancer, maintains high YAP protein levels in cervical cancer cells by preventing proteasome-dependent YAP degradation to drive cervical cancer cell proliferation. Results from human cervical cancer genomic databases and an accepted transgenic mouse model strongly support the clinical relevance of the discovered feed-forward signaling loop. Our study indicates that combined targeting of the Hippo and the ERBB signaling pathways represents a novel therapeutic strategy for prevention and treatment of cervical cancer. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Establishment and characterization of two cell lines from bluefin trevally Caranx melampygus.

    PubMed

    Zhao, Zhengshan; Lu, Yuanan

    2006-01-30

    Bluefin trevally Caranx melampygus Cuvier is a popular game fish and highly valued sea food with potential importance for aquaculture. To help establish this marine animal as an important aquacultural species in Hawaii and the Pacific and develop in vitro cell culture systems for long-term management and control of potential viral diseases 2 cell lines were established from body muscle (bluefin trevally muscles, BTMS) and fins (bluefin trevally fins, BTF). Primary culture of these cells was conducted at 25 degrees C using L-15 medium supplemented with 20% fetal bovine serum and various antibiotics. These cells have been serially subcultured 37 to 41 times since their initiation in June 2002. Growth of the bluefin trevally cells was serum-dependent at the time of the experiments and their plating efficiencies ranged from 11 to 28.2%. Comparative analysis showed that these bluefin trevally cells grew equally well in the media L-15 (Leibovitz medium), RPMI 1640, M199 and MEM (minimum essential medium), which are commonly used for cell cultures derived from aquatic animals and mammalian species. Examination of the early passage cells stored at -196 degrees C revealed a large percent (nearly 98%) of cell viability following a 6 mo storage in liquid nitrogen. Karyotyping analysis indicated that these bluefin trevally derived cell lines remained diploid with a chromosome count of 48 at passage 7 and 12. These 2 cell lines shared a same pattern of viral susceptibility and they were sensitive to infectious hematopoietic necrosis virus (IHNV), infectious pancreatic necrosis (IPN), spring viremia carp virus (SVCV), viral hemorrhagic septicemia virus (VHSV), and snakehead rhabdovirus (SHRV) but refractory to channel catfish virus (CCV) infection. These newly established cell lines are currently being used to facilitate the diagnosis of viral disease affecting marine fish aquaculture in Hawaii, and will be available for future isolation and study of bluefin trevally fish

  18. Inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling in the mouse blastocyst

    PubMed Central

    Kono, Kanako; Tamashiro, Dana Ann A.; Alarcon, Vernadeth B.

    2014-01-01

    Specification of the trophectoderm (TE) and inner cell mass (ICM) lineages in the mouse blastocyst correlates with cell position, as TE derives from outer cells whereas ICM from inner cells. Differences in position are reflected by cell polarization and Hippo signaling. Only in outer cells, the apical-basal cell polarity is established, and Hippo signaling is inhibited in such a manner that LATS1 and 2 (LATS1/2) kinases are prevented from phosphorylating YAP, a key transcriptional co-activator of the TE-specifying gene Cdx2. However, the molecular mechanisms that regulate these events are not fully understood. Here, we showed that inhibition of RHO-ROCK signaling enhances ICM and suppresses TE characteristics through activation of Hippo signaling and disruption of apical-basal polarity. Embryos treated with ROCK inhibitor Y-27632 exhibited elevated expression of ICM marker NANOG and reduced expression of CDX2 at the blastocyst stage. Y-27632-treated embryos failed to accumulate YAP in the nucleus, although it was rescued by concomitant inhibition of LATS1/2. Segregation between apical and basal polarity regulators, namely PARD6B, PRKCZ, SCRIB, and LLGL1, was dampened by Y-27632 treatment, whereas some of the polarization events at the late 8-cell stage such as compaction and apical localization of p-ERM and tyrosinated tubulin occurred normally. Similar abnormalities of Hippo signaling and apical-basal polarization were also observed in embryos that were treated with RHO GTPases inhibitor. These results suggest that RHO-ROCK signaling plays an essential role in regulating Hippo signaling and cell polarization to enable proper specification of the ICM and TE lineages. PMID:24997360

  19. Transitional Experiences of Post-16 Sports Education: Jack's Story

    ERIC Educational Resources Information Center

    Aldous, David C. R.; Sparkes, Andrew C.; Brown, David H. K.

    2014-01-01

    This paper explores the layered transitional experiences of a semi-professional athlete named Jack (a pseudonym) between the fields of professional sport and further and higher education. Our analysis is framed by the quadripartite framework of structuration and focuses on Jack's "in-situ" practices at his college and university in order…

  20. Jack bean (Canavalia ensiformis): nutrition related aspects and needed nutrition research.

    PubMed

    Akpapunam, M A; Sefa-Dedeh, S

    1997-01-01

    The nutritional characteristics and food potentials of jack bean (Canavalia ensiformis) have been reviewed. The bean is a good sources of protein, 23% to 34%, and carbohydrate 55%. It is also a good source of Ca, Zn, P, Mg, Cu and Ni. Jack bean protein is adequate in most essential amino acids with the exception of methionine and cystine which may be nutritionally limiting. Antinutritional and toxic factors including trypsin inhibitors, hemagglutinins, cyanogen glucosides, oligosaccharides and others are present in jack bean. Properly processed jack bean could be used to prepare some of the popular dishes made from cowpea, peanut, pigeon pea and soybean. Industrial products such as protein concentrates and isolates, starch, flakes, grits and flours can be produced from the bean. Further research is needed to identify varieties with high protein and nutritional quality. Development of new highly nutritious food products based on whole or processed jack bean should increase production and expand use.

  1. AmeriFlux US-Wi5 Mixed young jack pine (MYJP)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Jiquan

    This is the AmeriFlux version of the carbon flux data for the site US-Wi5 Mixed young jack pine (MYJP). Site Description - The Wisconsin Mixed Young Jack Pine site is located in the Washburn Ranger District of the northeastern section of Chequamegon National Forest. A member of the northern coniferous-deciduous biome, surveys from the mid-19th century indicate the region consisted of a mixed stand of red, white, and jack pines. After extensive timber harvesting, wildfires, and farming activity, the region turned into a fragmented mosaic of stands of various ages and composition. As an assemblage, the ten Wisconsin sites aremore » indicative of the successional stages of development in the predominant stand types of a physically homogeneous landscape. Clearcut on 40 to 70 year intervals, jack pine stands occupy approximately 13% of the region.« less

  2. Psychoanalysis of Jack London's "The Call of the Wild" and "White Fang"

    ERIC Educational Resources Information Center

    Yang, Hongyan

    2015-01-01

    "The Call of the Wild" and "White Fang" both are masterpieces of Jack London. The protagonists Buck and White Fang are the incarnation of Jack himself to some extent for the two novels reveal a great deal of the writer. This essay aims at psychoanalyzing Jack London's creative process, the Oedipus complex and the confliction…

  3. Using Black Light to Find Jack-Pine Budworm Egg Masses

    Treesearch

    Daniel T. Jennings

    1968-01-01

    Jack pine foliage infested with jack-pine budworm egg masses was examined under two kinds of light -- black light and a combination of natural and fluorescent light. Black light significantly increased the accuracy of count but not the efficiency of examination.

  4. Tropospheric carbon monoxide over the Pacific during HIPPO: two-way coupled simulation of GEOS-Chem and its multiple nested models

    NASA Astrophysics Data System (ADS)

    Yan, Y.-Y.; Lin, J.-T.; Kuang, Y.; Yang, D.; Zhang, L.

    2014-07-01

    Global chemical transport models (CTMs) are used extensively to study air pollution and transport at a global scale. These models are limited by coarse horizontal resolutions, not allowing for detailed representation of small-scale nonlinear processes over the pollutant source regions. Here we couple the global GEOS-Chem CTM and its three high-resolution nested models to simulate the tropospheric carbon monoxide (CO) over the Pacific Ocean during five HIAPER Pole-to-Pole Observations (HIPPO) campaigns between 2009 and 2011. We develop a two-way coupler, PKUCPL, to integrate simulation results for chemical constituents from the global model (at 2.5° long. × 2° lat.) and the three nested models (at 0.667° long. × 0.5° lat.) covering Asia, North America and Europe, respectively. The coupler obtains nested model results to modify the global model simulation within the respective nested domains, and simultaneously acquires global model results to provide lateral boundary conditions for the nested models. Compared to the global model alone, the two-way coupled simulation results in enhanced CO concentrations in the nested domains. Sensitivity tests suggest the enhancement to be a result of improved representation of the spatial distributions of CO, nitrogen oxides and non-methane volatile organic compounds, the meteorological dependence of natural emissions, and other resolution-dependent processes. The relatively long lifetime of CO allows for the enhancement to be accumulated and carried across the globe. We find that the two-way coupled simulation increases the global tropospheric mean CO concentrations in 2009 by 10.4%, with a greater enhancement at 13.3% in the Northern Hemisphere. Coincidently, the global tropospheric mean hydroxyl radical (OH) is reduced by 4.2% (as compared to the interannual variability of OH at 2.3%), resulting in a 4.2% enhancement in the methyl chloroform lifetime (MCF, via reaction with tropospheric OH). The resulting CO and OH

  5. Tropospheric carbon monoxide over the Pacific during HIPPO: two-way coupled simulation of GEOS-Chem and its multiple nested models

    NASA Astrophysics Data System (ADS)

    Yan, Y.-Y.; Lin, J.-T.; Kuang, Y.; Yang, D.; Zhang, L.

    2014-12-01

    Global chemical transport models (CTMs) are used extensively to study air pollution and transport at a global scale. These models are limited by coarse horizontal resolutions that do not allow for a detailed representation of small-scale nonlinear processes over the pollutant source regions. Here we couple the global GEOS-Chem CTM and its three high-resolution nested models to simulate the tropospheric carbon monoxide (CO) over the Pacific Ocean during five High-performance Instrumented Airborne Platform for Environmental Research (HIAPER) Pole-to-Pole Observations (HIPPO) campaigns between 2009 and 2011. We develop a two-way coupler, the PeKing University CouPLer (PKUCPL), allowing for the exchange and interaction of chemical constituents between the global model (at 2.5° long. × 2° lat.) and the three nested models (at 0.667° long. × 0.5° lat.) covering Asia, North America, and Europe. The coupler obtains nested model results to modify the global model simulation within the respective nested domains, and simultaneously acquires global model results to provide lateral boundary conditions (LBCs) for the nested models. Compared to the global model alone, the two-way coupled simulation results in enhanced CO concentrations in the nested domains. Sensitivity tests suggest the enhancement to be a result of improved representation of the spatial distributions of CO, nitrogen oxides, and non-methane volatile organic compounds, the meteorological dependence of natural emissions, and other resolution-dependent processes. The relatively long lifetime of CO allows for the enhancement to be accumulated and carried across the globe. We found that the two-way coupled simulation increased the global tropospheric mean CO concentrations in 2009 by 10.4%, with a greater enhancement at 13.3% in the Northern Hemisphere. Coincidently, the global tropospheric mean hydroxyl radical (OH) was reduced by 4.2%, resulting in a 4.2% enhancement in the methyl chloroform lifetime (MCF

  6. LOUSMA, JACK R. - WATER SURVIVAL TRAINING - FL

    NASA Image and Video Library

    1978-07-31

    S78-34037 (31 July 1978) --- Astronaut Jack R. Lousma, geared with a parachute, is pulled along behind a boat in Gulf waters at Homestead Air Force Base in Florida during a water survival training course attended by several NASA astronauts. The overall course is designed to familiarize astronauts with proper procedures to take in the event of ejection from an aircraft over water. Photo credit: NASA (NOTE: Since this photograph was made, astronaut Jack R. Lousma was named commander of STS-3, scheduled for launch in early spring of 1982.)

  7. Vector-valued Jack polynomials and wavefunctions on the torus

    NASA Astrophysics Data System (ADS)

    Dunkl, Charles F.

    2017-06-01

    The Hamiltonian of the quantum Calogero-Sutherland model of N identical particles on the circle with 1/r 2 interactions has eigenfunctions consisting of Jack polynomials times the base state. By use of the generalized Jack polynomials taking values in modules of the symmetric group and the matrix solution of a system of linear differential equations one constructs novel eigenfunctions of the Hamiltonian. Like the usual wavefunctions each eigenfunction determines a symmetric probability density on the N-torus. The construction applies to any irreducible representation of the symmetric group. The methods depend on the theory of generalized Jack polynomials due to Griffeth, and the Yang-Baxter graph approach of Luque and the author.

  8. Jack mechanism having positive stop means for its crank handle

    NASA Astrophysics Data System (ADS)

    Crockett, Watkins, IV; Baird, Bernard W.

    1995-04-01

    A jack mechanism having a crank handle that drives a linear motion control ball nut and threaded screw is presented. Two rods are included to provide a positive stop in each direction of the jack's limit so as to prevent overrun of the mechanism.

  9. Comparative analysis of a jack-up drilling unit with different leg systems

    NASA Astrophysics Data System (ADS)

    Ren, Xiangang; Bai, Yong; Jia, Lusheng

    2012-09-01

    The jack-up unit is one of the best drilling platforms in offshore oil fields with water depth shallower than 150 meters. As the most pivotal component of the jack-up unit, the leg system can directly affect the global performance of a jack-up unit. Investigation shows that there are three kinds of leg structure forms in the world now: the reverse K, X, and mixing types. In order to clarify the advantage and defects of each one, as well as their effect on the global performance of the jack-up unit, this paper commenced to study performance targets of a deepwater jack-up unit with different leg systems (X type, reverse K type, and mixing type). In this paper a typical leg scantling dimension and identical external loads were selected, detailed finite element snalysis (FEA) models were built to simulate the jack-up unit's structural behavior, and the multi-point constraint (MPC) element together with the spring element was used to deal with the boundary condition. Finally, the above problems were solved by comparative analysis of their main performance targets (including ultimate static strength, dynamic response, and weight).

  10. NOAA-GMD HIPPO data with a look towards transport in the troposphere

    NASA Astrophysics Data System (ADS)

    Dutton, G. S.; Moore, F. L.; Ray, E. A.; Elkins, J. W.; Hintsa, E. J.; Nance, J. D.; Hall, B. D.; Miller, B. R.; Montzka, S. A.; Hurst, D. F.; Sweeney, C.; Atlas, E. L.; Wofsy, S. C.

    2012-12-01

    During the three-year NSF sponsored HIPPO and START-08 campaigns, the National Oceanographic and Atmospheric Administration Earth System Research Laboratory Global Monitoring Division (NOAA/ESRL/GMD) maintained and took data from three basic instruments: NWAS (the NOAA Whole Air Sampler), UCATS (the UAS Chromatograph for Atmospheric Trace Species), and PANTHER (PAN and other Trace Hydrohalocarbon ExpeRiment). In this presentation we highlight this data set. The vertical and temporal coverage provided by ten Pole to Pole transits over the Pacific is unique to the HIPPO data set. The measured trace gases within this data set have lifetimes that span the time scales of transport within and across the bounder layer, free troposphere, and stratosphere. Within each of these regions, multiple trace gases were measured with either their major source or sink being contained within that region. Vertical and horizontal gradients are evident in the data that are consistent with variances in the source and sink regions, coupled with the dominant transport features such as inter-hemispheric exchange, upwelling and mixing, bounder layer trapping, stratospheric downwelling and intrusions, and transport of polluted air.

  11. 21 CFR 133.153 - Monterey cheese and monterey jack cheese.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Monterey cheese and monterey jack cheese. 133.153... (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.153 Monterey cheese and monterey jack cheese. (a) Description...

  12. 21 CFR 133.153 - Monterey cheese and monterey jack cheese.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Monterey cheese and monterey jack cheese. 133.153... (CONTINUED) FOOD FOR HUMAN CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.153 Monterey cheese and monterey jack cheese. (a) Description...

  13. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.

    2013-09-06

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis ofmore » epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.« less

  14. Comparison of improved Aura Tropospheric Emission Spectrometer (TES) CO 2 with HIPPO and SGP aircraft profile measurements

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kulawik, S. S.; Worden, J. R.; Wofsy, S. C.

    2012-01-01

    Comparisons are made between mid-tropospheric Tropospheric Emission Spectrometer (TES) carbon dioxide (CO{sub 2}) satellite measurements and ocean profiles from three Hiaper Pole-to-Pole Observations (HIPPO) campaigns and land aircraft profiles from the United States Southern Great Plains (SGP) Atmospheric Radiation Measurement (ARM) site over a 4-yr period. These comparisons are used to characterize the bias in the TES CO{sub 2} estimates and to assess whether calculated and actual uncertainties and sensitivities are consistent. The HIPPO dataset is one of the few datasets spanning the altitude range where TES CO{sub 2} estimates are sensitive, which is especially important for characterization of biases.more » We find that TES CO{sub 2} estimates capture the seasonal and latitudinal gradients observed by HIPPO CO{sub 2} measurements; actual errors range from 0.8–1.2 ppm, depending on the campaign, and are approximately 1.4 times larger than the predicted errors. The bias of TES versus HIPPO is within 0.85 ppm for each of the 3 campaigns; however several of the sub-tropical TES CO{sub 2} estimates are lower than expected based on the calculated errors. Comparisons of aircraft flask profiles, which are measured from the surface to 5 km, to TES CO{sub 2} at the SGP ARM site show good agreement with an overall bias of 0.1 ppm and rms of 1.0 ppm. We also find that the predicted sensitivity of the TES CO{sub 2} estimates is too high, which results from using a multi-step retrieval for CO{sub 2} and temperature. We find that the averaging kernel in the TES product corrected by a pressure-dependent factor accurately reflects the sensitivity of the TES CO{sub 2} product.« less

  15. Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis.

    PubMed

    Song, Yong; Fu, Jing; Zhou, Min; Xiao, Li; Feng, Xue; Chen, Hengxi; Huang, Wei

    2016-04-01

    The imbalance in cell proliferation and apoptosis is considered an important role in the pathogenesis of endometriosis, but the exact mechanisms remains unclear. A newly established signaling pathway–Hippo/Yes-associated protein (YAP) pathway plays a critical role in the proliferation and apoptosis processes. However, studies focusing on Hippo/YAP pathway and endometriosis are lacking. The objective was to explore the function of the Hippo/YAP pathway in endometriosis. The expression of YAP was first investigated in endometrium of women with or without endometriosis. The role of YAP in cell proliferation and apoptosis is identified by transfection of endometrial stromal cells (ESCs) in vitro, subsequent Verteporfin treatments in eutopic ESCs in vitro, and endometriosis animal model of nude mice in vivo. Our results revealed that increased expression of YAP and decreased expression of p-YAP in ectopic and eutopic endometrium compared with normal endometrium. YAP knockdown in eutopic ESCs decreased cell proliferation and enhanced cell apoptosis companied with decreased expression of TEAD1, CTGF, and B-cell lymphoma/leukemia (BCL)-2; whereas overexpression of YAP resulted in increased proliferation and decreased apoptosis of normal ESCs with increased expression of TEAD1, CTGF, and BCL-2. By chromatin immunoprecipitation qPCR CTGF and BCL-2 were identified as directly downstream target genes of YAP-TEAD1 active complex. Eutopic ESCs treated with Verteporfin revealed decreased proliferation and enhanced apoptosis whereas in endometriosis animal models of nude mice treated with Verteporfin, the size of endometriotic lesions was significantly reduced. Our study suggests that the Hippo/YAP-signaling pathway plays a critical role in the pathogenesis of endometriosis and should present a novel therapeutic method against endometriosis.

  16. Notch3 inhibits epithelial–mesenchymal transition by activating Kibra-mediated Hippo/YAP signaling in breast cancer epithelial cells

    PubMed Central

    Zhang, X; Liu, X; Luo, J; Xiao, W; Ye, X; Chen, M; Li, Y; Zhang, G-J

    2016-01-01

    Invasion, metastasis and chemoresistance are leading causes of death in breast cancer patients. A vital change of epithelial cells, epithelial–mesenchymal transition (EMT), is involved in these processes. Unfortunately, the molecular mechanisms controlling EMT remain to be elucidated. Our previous studies have shown that ectopic N3ICD expression inhibits EMT in MDA-MB-231, a triple-negative breast cancer (TNBC) epithelial cell line. To decipher the mechanism, we performed in-depth studies. Specifically, we found that overexpressing N3ICD transcriptionally upregulated the expression of Kibra, an upstream member of the Hippo pathway. Correspondingly, we also observed that phosphorylated Hippo pathway core kinases, including Lats1/2 and MST1/2, were increased and decreased by overexpressing and knocking down Notch3, respectively. Furthermore, we found that the oncogenic transcriptional coactivator yes-associated protein (YAP), which is negatively regulated by the Hippo pathway, was inhibited by overexpressing N3ICD in breast cancer epithelial cells. The ability of Kibra to inhibit EMT has been previously reported. We thus speculated that Notch3 inhibition of EMT is mediated by upregulated Kibra. To verify this hypothesis, a rescue experiment was performed. Evidently, the ability of Notch3 to inhibit EMT can be countered by knocking down Kibra expression. These data suggest that Notch3 inhibits EMT by activating the Hippo/YAP pathway by upregulating Kibra in breast cancer epithelial cells, and Kibra may be a downstream effector of Notch3. These findings deepen our understanding of EMT in both development and disease, and will undoubtedly help to provide new therapeutic strategies for interfering with cancer invasion and metastasis, especially for TNBC. PMID:27841855

  17. Jack Stenner: The Lexile King.

    ERIC Educational Resources Information Center

    Webster, Linda J.

    2000-01-01

    Traces the career of Jack Stenner. Stenner made the empirical discovery that observable readability could be entirely predicted from word familiarity and sentence length, and applied this "Lexile Framework"(R) to books and readers. Discusses the use of the Lexile Framework as a way to target specific readers. (SLD)

  18. CoJACK: A High-Level Cognitive Architecture with Demonstrations of Moderators, Variability, and Implications for Situation Awareness

    DTIC Science & Technology

    2012-01-01

    defined, to CoJACK (Ritter, Reifers, Klein, & Schoelles, 2007) based on task appraisal theory (e.g., Cannon, 1932; Lazarus & Folkman , 1984; Selye...Cambridge, MA: MIT Press. Lazarus , R. S., & Folkman , S. (1984). Stress, appraisal and coping. New York: Springer Publishing. Lovett, M. C., Daily, L...promising. 0 0.5 1 1.5 2 2.5 3 3.5 4 Java JACK Default CoJack CoJack Caffeine CoJack Challenged CoJack Threatened Agent Type Ta n k s D es tr o y e d

  19. The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression.

    PubMed

    Koontz, Laura M; Liu-Chittenden, Yi; Yin, Feng; Zheng, Yonggang; Yu, Jianzhong; Huang, Bo; Chen, Qian; Wu, Shian; Pan, Duojia

    2013-05-28

    The Hippo tumor suppressor pathway restricts tissue growth by inactivating the transcriptional coactivator Yki. Although Sd has been implicated as a DNA-binding transcription factor partner for Yki and can genetically account for gain-of-function Yki phenotypes, how Yki regulates normal tissue growth remains a long-standing puzzle because Sd, unlike Yki, is dispensable for normal growth in most Drosophila tissues. Here we show that the yki mutant phenotypes in multiple developmental contexts are rescued by inactivation of Sd, suggesting that Sd functions as a default repressor and that Yki promotes normal tissue growth by relieving Sd-mediated default repression. We further identify Tgi as a cofactor involved in Sd's default repressor function and demonstrate that the mammalian ortholog of Tgi potently suppresses the YAP oncoprotein in transgenic mice. These findings fill a major gap in Hippo-mediated transcriptional regulation and open up possibilities for modulating the YAP oncoprotein in cancer and regenerative medicine. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats

    PubMed Central

    Liu, Maojun; Liu, Shengquan; Tan, Wenting; Tang, Fen; Long, Junrong; Li, Zining; Liang, Biao; Chu, Chun; Yang, Jun

    2017-01-01

    Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)-generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid β-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins

  1. 14 CFR 23.507 - Jacking loads.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Vertical-load factor of 1.35 times the static reactions. (2) Fore, aft, and lateral load factors of 0.4 times the vertical static reactions. (b) The horizontal loads at the jack points must be reacted by...

  2. 14 CFR 23.507 - Jacking loads.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Vertical-load factor of 1.35 times the static reactions. (2) Fore, aft, and lateral load factors of 0.4 times the vertical static reactions. (b) The horizontal loads at the jack points must be reacted by...

  3. 14 CFR 23.507 - Jacking loads.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Vertical-load factor of 1.35 times the static reactions. (2) Fore, aft, and lateral load factors of 0.4 times the vertical static reactions. (b) The horizontal loads at the jack points must be reacted by...

  4. Regeneration of Cutover Jack Pine Stands

    Treesearch

    John W. Benzie

    1968-01-01

    Jack pine can be regenerated on mineral soil seedbeds by scattering cone-bearing branches or repellent-treated seed. On some areas where competition develops, the seedlings may need to be released between the third and fifth years.

  5. 14 CFR 23.507 - Jacking loads.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Vertical-load factor of 1.35 times the static reactions. (2) Fore, aft, and lateral load factors of 0.4 times the vertical static reactions. (b) The horizontal loads at the jack points must be reacted by...

  6. Students Learning Physics While Lifting Themselves: A Simple Analysis of a Scissors Jack

    ERIC Educational Resources Information Center

    Haugland, Ole Anton

    2017-01-01

    Every time I have to jack up my car, I am a bit surprised by how slowly the scissors jack works the higher I raise it, and close to maximum height I need very little force to turn the crank. This agrees well with the principle of simple machines. Since I have to jack up my car at least twice a year to change between winter tires and summer tires,…

  7. Hydraulically-operated pump jack with chain drive

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ratell Jr., R. E.

    1985-02-05

    My invention relates to pumping apparatus, particularly to a hydraulically-operated pump jack for oil, brine water and the like. The apparatus is fabricated from steel plate to make a strong, but light-weight tower which may be easily transported from one site to another by a small boom truck or gin pole truck. In contrast to pump jacks of the walking beam type which are massive in size, my improved pump jack is compact and is seated on and secured directly to the head of an oil well casing. A vertically-arranged hydraulic cylinder has its piston rod connected to a crossmore » head on which a pair of sprockets are journalled. Chains pass around respective sprockets, one reach of each chain extending upwardly and is anchored to a stationary part of the tower. The other reach of each chain extends upwardly and over and around an upper sprocket journalled on a shaft carried by the upper end of the tower, each chain then extending downwardly to a yoke to which the polish rod is connected. This arrangement will result in a 2 to 1 ratio between the movement of the polish rod and the stroke of the hydraulic cylinder.« less

  8. Jack Michael's Motivation

    ERIC Educational Resources Information Center

    Miguel, Caio F.

    2013-01-01

    Among many of Jack Michael's contributions to the field of behavior analysis is his behavioral account of motivation. This paper focuses on the concept of "motivating operation" (MO) by outlining its development from Skinner's (1938) notion of "drive." Conceptually, Michael's term helped us change our focus on…

  9. Jack Dymond's "Fingerprints" on Sediment Chemistry, Biogeochemical Fluxes, and my Career

    NASA Astrophysics Data System (ADS)

    Leinen, M.

    2004-12-01

    I first met Jack Dymond as a graduate student at Oregon State University. He wasn't my thesis advisor. He wasn't even on my committee. But his ever so gentle counsel and his low key advice did much to shape my career, as a student, as a scientist, and later as an administrator of science. At the time, Jack was wading through the analysis of a very large number of surface sediment samples from the Nazca Plate as part of an IDOE project. The number and density of sampling was extraordinary for the time and his work showed that the geochemistry of the sediments could be deconvolved to understand the contributions of sediment sources over the entire plate. I had been planning to analyze DSDP samples from the equatorial Pacific to understand the history of siliceous sedimentation in that region and I began to talk with Jack about how I could use geochemical signatures to estimate the non-biogenic fraction of the sediment. When Jack's Nazca Plate paper came out, Debra Stakes and I decided to analyze all of my sample residues for the same elements that Jack had studied. In the only piece of bad advice that he ever gave me, Jack told me that it was a waste of time because there wouldn't be high enough concentrations of transition metals in the calcareous and siliceous sediments to measure. We insisted and Jack, in typical fashion, agreed to pay for reagents and give us instrument time without charge anyway. The larger than expected concentrations, and the even more surprising match between the accumulation rates of some the metals and the accumulation rates of biogenic sediment were the subject of many discussions, all of which ended in the need for more information on the composition, fluxes and transformations of biogenic sediment in the water column and in recent sediments. This, of course, became another of Jack's specialties: his designs for sediment traps were important contributions to the evolution of this important sampling device. His studies of fluxes in a wide

  10. Jacking mechanism for upper internals structure of a liquid metal nuclear reactor

    DOEpatents

    Gillett, James E.; Wineman, Arthur L.

    1984-01-01

    A jacking mechanism for raising the upper internals structure of a liquid metal nuclear reactor which jacking mechanism uses a system of gears and drive shafts to transmit force from a single motor to four mechanically synchronized ball jacks to raise and lower support columns which support the upper internals structure. The support columns have a pin structure which rides up and down in a slot in a housing fixed to the reactor head. The pin has two locking plates which can be rotated around the pin to bring bolt holes through the locking plates into alignment with a set of bolt holes in the housing, there being a set of such housing bolt holes corresponding to both a raised and a lowered position of the support column. When the locking plate is so aligned, a surface of the locking plate mates with a surface in the housing such that the support column is then supported by the locking plate and not by the ball jacks. Since the locking plates are to be installed and bolted to the housing during periods of reactor operation, the ball jacks need not be sized to react the large forces which occur or potentially could occur on the upper internals structure of the reactor during operation. The locking plates react these loads. The ball jacks, used only during refueling, can be smaller, which enable conventionally available equipment to fulfill the precision requirements for the task within available space.

  11. Alternate Host of Jack Pine Needle rust in Northern Minnesota

    Treesearch

    Ralph L. Anderson; Neil A. Anderson

    1978-01-01

    The pine needle rust of jack pine on the Little Sioux Burn in northeastern Minnesota infected large-leaf aster but not goldenrod. The rust was most severe when asters were abundant on the plots. Les than 10 percent of the jack pine were infected over a 3-year period when asters were more than 10 feet (3.05 m) from the mil-acre plots

  12. The Hippo pathway: key interaction and catalytic domains in organ growth control, stem cell self-renewal and tissue regeneration.

    PubMed

    Cherrett, Claire; Furutani-Seiki, Makoto; Bagby, Stefan

    2012-01-01

    The Hippo pathway is a conserved pathway that interconnects with several other pathways to regulate organ growth, tissue homoeostasis and regeneration, and stem cell self-renewal. This pathway is unique in its capacity to orchestrate multiple processes, from sensing to execution, necessary for organ expansion. Activation of the Hippo pathway core kinase cassette leads to cytoplasmic sequestration of the nuclear effectors YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), consequently disabling their transcriptional co-activation function. Components upstream of the core kinase cassette have not been well understood, especially in vertebrates, but are gradually being elucidated and include cell polarity and cell adhesion proteins.

  13. Observations of a stratospheric depletion and annual mean interhemispheric gradient in the atmospheric Ar/N2 ratio from the HIPPO Global campaign

    NASA Astrophysics Data System (ADS)

    Bent, J. D.; Keeling, R. F.; Stephens, B. B.; Wofsy, S. C.; Daube, B. C.; Kort, E. A.; Pittman, J. V.; Jimenez-Pizarro, R.; Santoni, G.

    2014-12-01

    The atmospheric Ar/N2 ratio varies on a seasonal basis due to temperature-dependent solubility changes in the surface ocean. Low signal:noise ratios, limited vertical coverage, and sampler-sampler offsets have historically hampered characterization of vertical and inter-hemispheric gradients. We present data from the HIPPO Global campaign (2009-11) showing that Ar/N2 and interannually-detrended N2O correlate well in the lower stratosphere, suggesting that, as stratospheric air ages and loses N2O to photolysis and photo-oxidation, it also gradually loses argon to gravity as the heavier atom preferentially "rains out" of the air parcel. The HIPPO Ar/N2 data from the lower troposphere also resolve seasonal cycles in each hemisphere, as well as a gradient in the annual mean between hemispheres, with higher values in the southern hemisphere. The HIPPO cycles and inter-hemispheric gradient are in good agreement with data from surface stations.

  14. Additive and non-additive genetic components of the jack male life history in Chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Forest, Adriana R; Semeniuk, Christina A D; Heath, Daniel D; Pitcher, Trevor E

    2016-08-01

    Chinook salmon, Oncorhynchus tshawytscha, exhibit alternative reproductive tactics (ARTs) where males exist in two phenotypes: large "hooknose" males and smaller "jacks" that reach sexual maturity after only 1 year in seawater. The mechanisms that determine "jacking rate"-the rate at which males precociously sexually mature-are known to involve both genetics and differential growth rates, where individuals that become jacks exhibit higher growth earlier in life. The additive genetic components have been studied and it is known that jack sires produce significantly more jack offspring than hooknose sires, and vice versa. The current study was the first to investigate both additive and non-additive genetic components underlying jacking through the use of a full-factorial breeding design using all hooknose sires. The effect of dams and sires descendant from a marker-assisted broodstock program that identified "high performance" and "low performance" lines using growth- and survival-related gene markers was also studied. Finally, the relative growth of jack, hooknose, and female offspring was examined. No significant dam, sire, or interaction effects were observed in this study, and the maternal, additive, and non-additive components underlying jacking were small. Differences in jacking rates in this study were determined by dam performance line, where dams that originated from the low performance line produced significantly more jacks. Jack offspring in this study had a significantly larger body size than both hooknose males and females starting 1 year post-fertilization. This study provides novel information regarding the genetic architecture underlying ARTs in Chinook salmon that could have implications for the aquaculture industry, where jacks are not favoured due to their small body size and poor flesh quality.

  15. Students Learning Physics While Lifting Themselves: A Simple Analysis of a Scissors Jack

    NASA Astrophysics Data System (ADS)

    Haugland, Ole Anton

    2017-02-01

    Every time I have to jack up my car, I am a bit surprised by how slowly the scissors jack works the higher I raise it, and close to maximum height I need very little force to turn the crank. This agrees well with the principle of simple machines. Since I have to jack up my car at least twice a year to change between winter tires and summer tires, I thought it was time to take a closer look at the physics behind the process. And like most physics teachers, I am always looking for new ideas for my teaching. In this note I will present a few ideas on how a jack can be a topic in physics teaching.

  16. The Human Adenovirus Type 5 E4orf4 Protein Targets Two Phosphatase Regulators of the Hippo Signaling Pathway

    PubMed Central

    Mui, Melissa Z.; Zhou, Yiwang; Blanchette, Paola; Chughtai, Naila; Knight, Jennifer F.; Gruosso, Tina; Papadakis, Andreas I.; Huang, Sidong; Park, Morag; Gingras, Anne-Claude

    2015-01-01

    ABSTRACT When expressed alone at high levels, the human adenovirus E4orf4 protein exhibits tumor cell-specific p53-independent toxicity. A major E4orf4 target is the B55 class of PP2A regulatory subunits, and we have shown recently that binding of E4orf4 inhibits PP2AB55 phosphatase activity in a dose-dependent fashion by preventing access of substrates (M. Z. Mui et al., PLoS Pathog 9:e1003742, 2013, http://dx.doi.org/10.1371/journal.ppat.1003742). While interaction with B55 subunits is essential for toxicity, E4orf4 mutants exist that, despite binding B55 at high levels, are defective in cell killing, suggesting that other essential targets exist. In an attempt to identify additional targets, we undertook a proteomics approach to characterize E4orf4-interacting proteins. Our findings indicated that, in addition to PP2AB55 subunits, ASPP-PP1 complex subunits were found among the major E4orf4-binding species. Both the PP2A and ASPP-PP1 phosphatases are known to positively regulate effectors of the Hippo signaling pathway, which controls the expression of cell growth/survival genes by dephosphorylating the YAP transcriptional coactivator. We find here that expression of E4orf4 results in hyperphosphorylation of YAP, suggesting that Hippo signaling is affected by E4orf4 interactions with PP2AB55 and/or ASPP-PP1 phosphatases. Furthermore, knockdown of YAP1 expression was seen to enhance E4orf4 killing, again consistent with a link between E4orf4 toxicity and inhibition of the Hippo pathway. This effect may in fact contribute to the cancer cell specificity of E4orf4 toxicity, as many human cancer cells rely heavily on the Hippo pathway for their enhanced proliferation. IMPORTANCE The human adenovirus E4orf4 protein has been known for some time to induce tumor cell-specific death when expressed at high levels; thus, knowledge of its mode of action could be of importance for development of new cancer therapies. Although the B55 form of the phosphatase PP2A has long been

  17. Emory University: High-Throughput Protein-Protein Interaction Analysis for Hippo Pathway Profiling | Office of Cancer Genomics

    Cancer.gov

    The CTD2 Center at Emory University used high-throughput protein-protein interaction (PPI) mapping for Hippo signaling pathway profiling to rapidly unveil promising PPIs as potential therapeutic targets and advance functional understanding of signaling circuitry in cells. Read the abstract.

  18. Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity

    PubMed Central

    Doddrell, Robin D.S.; Edwards, Philip; Morrison, Helen

    2017-01-01

    Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS. PMID:28137778

  19. Emerging role of Hippo signalling in pancreatic biology: YAP re-expression and plausible link to islet cell apoptosis and replication.

    PubMed

    Sharma, Anjana; Yerra, Veera Ganesh; Kumar, Ashutosh

    2017-02-01

    Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size. Nuclear recruitment of YAP/TAZ (Yes-associated protein/transcriptional co-activator with PDZ-binding motif), a mammalian analogue of Yorkie protein found in Drosophila, activates cell proliferation and inhibits apoptosis. YAP was found to regulate early pancreatic development followed by downregulation during Ngn3-specific endocrine lineage maturation corresponding to their mitotic quiescence. Recent evidences have shown that optimum modulation of upstream kinases in the Hippo signalling pathway may lead to apoptosis inhibition and renewal of progenitor as well as stem cells in case of tissue or cell injury. This article reviews the evidences linking the role of various components of the Hippo pathway to pancreatic regeneration. In particular, the focus is on the beneficial role of induced YAP expression and its nuclear distribution on apoptosis and replication of adult pancreatic β islets. This approach may be of immense significance towards our fight against diabetes; thus, more insightful research is warranted in the area of Hippo signalling pathway and its involvement in pancreatic regeneration. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  20. Recollections of Jack Michael and the Application of Skinner's Analysis of Verbal Behavior

    ERIC Educational Resources Information Center

    Sundberg, Mark L.

    2017-01-01

    Jack Michael offered a course on verbal behavior almost every year throughout his teaching career. Jack was also interested in the application of Skinner's work and in 1976 began to offer a graduate course at Western Michigan University titled Verbal Behavior Applications. Jack and his students pursued the application of Skinner's work on verbal…

  1. Astronaut Jack R. Lousma and family

    NASA Image and Video Library

    1971-12-01

    S72-31432 (November 1972) --- Astronaut Jack R. Lousma poses for a family portrait with his wife, Gratia Kay, and their three children, left to right, Mary 4; Timothy, 9; and Matthew, 7. Lousma is the pilot for the Skylab 3 or second manned Skylab mission. Photo credit: NASA

  2. Follow up of injected polyurethane slab jacking.

    DOT National Transportation Integrated Search

    2003-08-01

    GLENN JACKSON BRIDGE FOLLOW-UP REPORT The elevation monitoring in the report entitled Injected Polyurethane Slab Jacking (Soltesz 2000) is continued in this current report. The elevations of the concrete slabs are being monitored to see if polyuretha...

  3. A novel acetylation cycle of transcription co-activator Yes-associated protein that is downstream of Hippo pathway is triggered in response to SN2 alkylating agents.

    PubMed

    Hata, Shoji; Hirayama, Jun; Kajiho, Hiroaki; Nakagawa, Kentaro; Hata, Yutaka; Katada, Toshiaki; Furutani-Seiki, Makoto; Nishina, Hiroshi

    2012-06-22

    Yes-associated protein (YAP) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes. Although cytoplasmic retention of YAP is known to be mediated by Hippo pathway-dependent phosphorylation, post-translational modifications that regulate YAP in the nucleus remain unclear. Here we report the discovery of a novel cycle of acetylation/deacetylation of nuclear YAP induced in response to S(N)2 alkylating agents. We show that after treatment of cells with the S(N)2 alkylating agent methyl methanesulfonate, YAP phosphorylation mediated by the Hippo pathway is markedly reduced, leading to nuclear translocation of YAP and its acetylation. This YAP acetylation occurs on specific and highly conserved C-terminal lysine residues and is mediated by the nuclear acetyltransferases CBP (CREB binding protein) and p300. Conversely, the nuclear deacetylase SIRT1 is responsible for YAP deacetylation. Intriguingly, we found that YAP acetylation is induced specifically by S(N)2 alkylating agents and not by other DNA-damaging stimuli. These results identify a novel YAP acetylation cycle that occurs in the nucleus downstream of the Hippo pathway. Intriguingly, our findings also indicate that YAP acetylation is involved in responses to a specific type of DNA damage.

  4. A Novel Acetylation Cycle of Transcription Co-activator Yes-associated Protein That Is Downstream of Hippo Pathway Is Triggered in Response to SN2 Alkylating Agents*

    PubMed Central

    Hata, Shoji; Hirayama, Jun; Kajiho, Hiroaki; Nakagawa, Kentaro; Hata, Yutaka; Katada, Toshiaki; Furutani-Seiki, Makoto; Nishina, Hiroshi

    2012-01-01

    Yes-associated protein (YAP) is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes. Although cytoplasmic retention of YAP is known to be mediated by Hippo pathway-dependent phosphorylation, post-translational modifications that regulate YAP in the nucleus remain unclear. Here we report the discovery of a novel cycle of acetylation/deacetylation of nuclear YAP induced in response to SN2 alkylating agents. We show that after treatment of cells with the SN2 alkylating agent methyl methanesulfonate, YAP phosphorylation mediated by the Hippo pathway is markedly reduced, leading to nuclear translocation of YAP and its acetylation. This YAP acetylation occurs on specific and highly conserved C-terminal lysine residues and is mediated by the nuclear acetyltransferases CBP (CREB binding protein) and p300. Conversely, the nuclear deacetylase SIRT1 is responsible for YAP deacetylation. Intriguingly, we found that YAP acetylation is induced specifically by SN2 alkylating agents and not by other DNA-damaging stimuli. These results identify a novel YAP acetylation cycle that occurs in the nucleus downstream of the Hippo pathway. Intriguingly, our findings also indicate that YAP acetylation is involved in responses to a specific type of DNA damage. PMID:22544757

  5. 3-D habitat suitability of jack mackerel Trachurus murphyi in the Southeastern Pacific, a comprehensive study

    NASA Astrophysics Data System (ADS)

    Bertrand, Arnaud; Habasque, Jérémie; Hattab, Tarek; Hintzen, Niels T.; Oliveros-Ramos, Ricardo; Gutiérrez, Mariano; Demarcq, Hervé; Gerlotto, François

    2016-08-01

    South Pacific jack mackerel, Trachurus murphyi, has an ocean-scale distribution, from the South American coastline to New Zealand and Tasmania. This fish, captured by Humans since the Holocene, is nowadays heavily exploited and its population has decreased substantially since the mid-1990s. The uncertainty associated to jack mackerel population structure currently hampers management. Several hypotheses have been proposed from a single population up to several discrete populations. Still no definitive answer was given. Determining how environmental conditions drive jack mackerel distribution can provide insights on its population structure. To do so, here we performed in three steps. First, we used satellite data to develop a statistical model of jack mackerel horizontal habitat suitability. Model predictions based on interaction between temperature and chlorophyll-a match the observed jack mackerel distribution, even during extreme El Niño event. Second, we studied the impact of oxygen and show that jack mackerel distribution and abundance is correlated to oxygen over a wide variety of scales and avoid low oxygen areas and periods. Third, on the basis of the above we built a conceptual 3D model of jack mackerel habitat in the Southeastern Pacific. We reveal the presence of a low suitable habitat along the Chilean and Peruvian coast, figuratively presenting a closed door caused by a gap in the horizontal habitat at ∼19-22°S and a shallow oxycline off south-centre Peru. This kind of situation likely occurs on a seasonal basis, in austral summer but also at longer temporal scales. A lack of exchanges at some periods/seasons partially isolate jack mackerel distributed off Peru. On the other hand the continuity in the habitat during most of the year explains why exchanges occur. We conclude that the more likely population structure for jack mackerel is a pelagic metapopulation.

  6. 4. Unit 4 Turbine Pit Oil Jacking Pump and Wicket ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Unit 4 Turbine Pit Oil Jacking Pump and Wicket Gate Linkages, view to the north. The jacking pump, located along the wall on the left side of photograph, is used for pumping oil to lift the thrust bearing prior to starting the unit. Note the wicket gate linkages attached to the operating ring and visible in the lower center of the photograph. - Washington Water Power Clark Fork River Cabinet Gorge Hydroelectric Development, Powerhouse, North Bank of Clark Fork River at Cabinet Gorge, Cabinet, Bonner County, ID

  7. 65th birthday Jack Steinberger

    ScienceCinema

    None

    2017-12-09

    Laudatio pour Jack Steinberger né le 25 mai 1921, à l'occasion de son 65me anniversaire et sa retraite officielle, pour sa précieuse collaboration au Cern. Néanmoins son principal activité continuera comme avant dans sa recherche au Cern. Plusieurs orateurs prennent la parole (p.ex. E.Picasso) pour le féliciter et lui rendre hommage

  8. PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia.

    PubMed

    Liu, Wenying Angela; Chen, She; Li, Zhizhong; Lee, Choong Heon; Mirzaa, Ghayda; Dobyns, William B; Ross, M Elizabeth; Zhang, Jiangyang; Shi, Song-Hai

    2018-06-01

    Proper organization and orderly mitosis of radial glial progenitors (RGPs) drive the formation of a laminated mammalian cortex in the correct size. However, the molecular underpinnings of the intricate process remain largely unclear. Here we show that RGP behavior and cortical development are controlled by temporally distinct actions of partitioning-defective 3 (PARD3) in concert with dynamic HIPPO signaling. RGPs lacking PARD3 exhibit developmental stage-dependent abnormal switches in division mode, resulting in an initial overproduction of RGPs located largely outside the ventricular zone at the expense of deep-layer neurons. Ectopically localized RGPs subsequently undergo accelerated and excessive neurogenesis, leading to the formation of an enlarged cortex with massive heterotopia and increased seizure susceptibility. Simultaneous removal of HIPPO pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) suppresses cortical enlargement and heterotopia formation. These results define a dynamic regulatory program of mammalian cortical development and highlight a progenitor origin of megalencephaly with ribbon heterotopia and epilepsy. © 2018 Liu et al.; Published by Cold Spring Harbor Laboratory Press.

  9. Melatonin and Hippo Pathway: Is There Existing Cross-Talk?

    PubMed

    Lo Sardo, Federica; Muti, Paola; Blandino, Giovanni; Strano, Sabrina

    2017-09-06

    Melatonin is an indolic hormone that regulates a plethora of functions ranging from the regulation of circadian rhythms and antioxidant properties to the induction and maintenance of tumor suppressor pathways. It binds to specific receptors as well as to some cytosolic proteins, leading to several cellular signaling cascades. Recently, the involvement of melatonin in cancer insurgence and progression has clearly been demonstrated. In this review, we will first describe the structure and functions of melatonin and its receptors, and then discuss both molecular and epidemiological evidence on melatonin anticancer effects. Finally, we will shed light on potential cross-talk between melatonin signaling and the Hippo signaling pathway, along with the possible implications for cancer therapy.

  10. A Bibliographic Tribute to Jack Michael

    ERIC Educational Resources Information Center

    Esch, Barbara E.; Esch, John W.

    2016-01-01

    "In the late 1950's, Jack Michael, a bright but irritating young psychology instructor, moved from the Universities of Kansas to Houston to Arizona State. Along the way he befriended two nontraditional students, protected them through their Ph.D. programs, and turned them loose on the world: Teodoro Ayllon…and Montrose Wolf…" (Risley,…

  11. Load capacity, failure mode and design criteria investigation of sand jacks : full scale load testing of sand jacks.

    DOT National Transportation Integrated Search

    2008-12-01

    A sand-jack is a sand filled container used as a component of cast-in-place bridge false-work. The sand filler facilitates the removal of the false-work by allowing slow and controlled lowering of the bracing that has become wedged beneath the new br...

  12. Nutrient accumulation in planted red and jack pine.

    Treesearch

    David H. Alban

    1988-01-01

    Compares nutrient accumulation in adjacent plantations of red and jack pine in the upper Great Lakes. Describes equations developed to predict biomass and nutrient accumulation based on stand basal area and height.

  13. Tough new jack-up for rough seas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1984-01-01

    Rowan Company's new deepwater jack-up, Rowan Gorilla I, is scheduled to spud its initial well off the east coast of Canada later this month for a consortium of oil companies including Bow Valley-Husky and ATS Exploration Ltd. The new rig's class designation--Gorilla--reflects designers' expectations for the drilling unit that is suited to work in virtually all ice-free hostile environmental areas of the world. Rowan's confidence in the design, built by Marathon LeTourneau's Vicksburg, Mississippi yard, is reiterated by the fact that two additional rigs in the Gorilla class are being built. Rowan Gorilla II is being constructed at Marathon's Singaporemore » yard, and the Rowan Gorilla III is in early construction stages at the firm's Vicksburg yard. The three Gorilla-class rigs will cost in excess of $85 million each, including owner-furnished drilling equipment. This, according to owners, will make them among the costliest jack-ups in the world. Another record being claimed by the Gorilla-class drilling units is that they are the largest jack-ups in the world. Fully outfitted, a Gorilla contains 16,000 tons of steel. Its triangular hull measures 297 ft from bow to stern and 292 ft across the stern. The rig has a variable load of 2,750 tons for drilling consumables and 42,265 sq ft of deck space. Its ample storage capacity, along with its 503-ft leg length and certain design features, makes the rig compatible with hostile offshore areas, where it can continue drilling for long periods unattended.« less

  14. Lively Jack-O'-Lantern Still Life

    ERIC Educational Resources Information Center

    Sanzaro, Christy

    2010-01-01

    Pumpkin carving is a favorite classroom activity. Around late October, the halls are filled with the sour smell of raw pumpkin innards, as parents, teachers and students are up to their elbows in yellowish strings and slime. These round, orange squash are transformed into jack-o'-lanterns that are placed around the school. The day after Halloween,…

  15. Analysis of transpacific transport of black carbon during HIPPO-3: implications for black carbon aging

    NASA Astrophysics Data System (ADS)

    Shen, Z.; Liu, J.; Horowitz, L. W.; Henze, D. K.; Fan, S.; Levy, H., II; Mauzerall, D. L.; Lin, J.-T.; Tao, S.

    2014-06-01

    Long-range transport of black carbon (BC) is a growing concern as a result of the efficiency of BC in warming the climate and its adverse impact on human health. We study transpacific transport of BC during HIPPO-3 using a combination of inverse modeling and sensitivity analysis. We use the GEOS-Chem chemical transport model and its adjoint to constrain Asian BC emissions and estimate the source of BC over the North Pacific. We find that different sources of BC dominate the transport to the North Pacific during the southbound (29 March 2010) and northbound (13 April 2010) measurements in HIPPO-3. While biomass burning in Southeast Asia (SE) contributes about 60% of BC in March, more than 90% of BC comes from fossil fuel and biofuel combustion in East Asia (EA) during the April mission. GEOS-Chem simulations generally resolve the spatial and temporal variation of BC concentrations over the North Pacific, but are unable to reproduce the low and high tails of the observed BC distribution. We find that the optimized BC emissions derived from inverse modeling fail to improve model simulations significantly. This failure indicates that uncertainties in BC removal as well as transport, rather than in emissions, account for the major biases in GEOS-Chem simulations of BC over the North Pacific. The aging process, transforming BC from hydrophobic into hydrophilic form, is one of the key factors controlling wet scavenging and remote concentrations of BC. Sensitivity tests on BC aging (ignoring uncertainties of other factors controlling BC long range transport) suggest that in order to fit HIPPO-3 observations, the aging timescale of anthropogenic BC from EA may be several hours (faster than assumed in most global models), while the aging process of biomass burning BC from SE may occur much slower, with a timescale of a few days. To evaluate the effects of BC aging and wet deposition on transpacific transport of BC, we develop an idealized model of BC transport. We find that

  16. A Heavy-Duty Jack for a Giant Task

    NASA Image and Video Library

    2010-11-03

    A major refurbishment of the giant Mars antenna at NASA Deep Space Network Goldstone Deep Space Communications Complex in California Mojave Desert required workers to jack up millions of pounds of delicate scientific equipment.

  17. Full scale load testing of sand-jacks.

    DOT National Transportation Integrated Search

    2006-06-01

    A sand-jack is a sand filled container used as a component of cast-in-place bridge false-work. The sand filler facilitates the removal of the false-work by allowing slow and controlled lowering of the bracing that has become wedged beneath the new br...

  18. Topological color codes on Union Jack lattices: a stable implementation of the whole Clifford group

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Katzgraber, Helmut G.; Theoretische Physik, ETH Zurich, CH-8093 Zurich; Bombin, H.

    We study the error threshold of topological color codes on Union Jack lattices that allow for the full implementation of the whole Clifford group of quantum gates. After mapping the error-correction process onto a statistical mechanical random three-body Ising model on a Union Jack lattice, we compute its phase diagram in the temperature-disorder plane using Monte Carlo simulations. Surprisingly, topological color codes on Union Jack lattices have a similar error stability to color codes on triangular lattices, as well as to the Kitaev toric code. The enhanced computational capabilities of the topological color codes on Union Jack lattices with respectmore » to triangular lattices and the toric code combined with the inherent robustness of this implementation show good prospects for future stable quantum computer implementations.« less

  19. Astronaut Jack Fischer at Rock Creek Park

    NASA Image and Video Library

    2017-11-04

    NASA astronaut Jack Fischer answers a question from the audience, Saturday, Nov. 4, 2017 at the Rock Creek Park Nature Center and Planetarium in Washington, DC. During his 136 day mission aboard the ISS, Fischer conducted two spacewalks and hundreds of scientific experiments. Photo Credit: (NASA/Joel Kowsky)

  20. Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling

    PubMed Central

    Archibald, Andrew; Al-Masri, Maia; Liew-Spilger, Alyson; McCaffrey, Luke

    2015-01-01

    Epithelial cells are major sites of malignant transformation. Atypical protein kinase C (aPKC) isoforms are overexpressed and activated in many cancer types. Using normal, highly polarized epithelial cells (MDCK and NMuMG), we report that aPKC gain of function overcomes contact inhibited growth and is sufficient for a transformed epithelial phenotype. In 2D cultures, aPKC induced cells to grow as stratified epithelia, whereas cells grew as solid spheres of nonpolarized cells in 3D culture. aPKC associated with Mst1/2, which uncoupled Mst1/2 from Lats1/2 and promoted nuclear accumulation of Yap1. Of importance, Yap1 was necessary for aPKC-mediated overgrowth but did not restore cell polarity defects, indicating that the two are separable events. In MDCK cells, Yap1 was sequestered to cell–cell junctions by Amot, and aPKC overexpression resulted in loss of Amot expression and a spindle-like cell phenotype. Reexpression of Amot was sufficient to restore an epithelial cobblestone appearance, Yap1 localization, and growth control. In contrast, the effect of aPKC on Hippo/Yap signaling and overgrowth in NMuMG cells was independent of Amot. Finally, increased expression of aPKC in human cancers strongly correlated with increased nuclear accumulation of Yap1, indicating that the effect of aPKC on transformed growth by deregulating Hippo/Yap1 signaling may be clinically relevant. PMID:26269582

  1. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

    PubMed

    Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

    2014-06-16

    Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. An experimental study of the mechanism of failure of rocks under borehole jack loading

    NASA Technical Reports Server (NTRS)

    Van, T. K.; Goodman, R. E.

    1971-01-01

    Laboratory and field tests with an experimental jack and an NX-borehole jack are reported. The following conclusions were made: Under borehole jack loading, a circular opening in a brittle solid fails by tensile fracturing when the bearing plate width is not too small. Two proposed contact stress distributions can explain the mechanism of tensile fracturing. The contact stress distribution factor is a material property which can be determined experimentally. The borehole tensile strength is larger than the rupture flexural strength. Knowing the magnitude and orientation of the in situ stress field, borehole jack test results can be used to determine the borehole tensile strength. Knowing the orientation of the in situ stress field and the flexural strength of the rock substance, the magnitude of the in situ stress components can be calculated. The detection of very small cracks is essential for the accurate determination of the failure loads which are used in the calculation of strengths and stress components.

  3. Kraft pulp from budworm-infested jack pine

    Treesearch

    J. Y. Zhu; Gary C. Myers

    2006-01-01

    This study evaluated the quality of kraft pulp from bud-worm-infested jack pine. The logs were classified as merchantable live, suspect, or merchantable dead. Raw materials were evaluated through visual inspection, analysis of the chemical composition, SilviScan measurement of the density, and measurement of the tracheid length. Unbleached pulps were then refined using...

  4. 75 FR 32357 - Gallatin National Forest; Montana; Jack Rabbit to Big Sky Meadow Village 161 kV Transmission Line...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... DEPARTMENT OF AGRICULTURE Forest Service Gallatin National Forest; Montana; Jack Rabbit to Big Sky... electric transmission line. The upgraded 161-kV transmission line would connect the existing Jack Rabbit... with eight regional entities to improve the reliability of the bulk power system. The Jack Rabbit to...

  5. WWC3 regulates the Wnt and Hippo pathways via Dishevelled proteins and large tumour suppressor 1, to suppress lung cancer invasion and metastasis.

    PubMed

    Han, Qiang; Lin, Xuyong; Zhang, Xiupeng; Jiang, Guiyang; Zhang, Yong; Miao, Yuan; Rong, Xuezhu; Zheng, Xiaoying; Han, Yong; Han, Xu; Wu, Jingjing; Kremerskothen, Joachim; Wang, Enhua

    2017-08-01

    The scaffolding protein WWC (WW and C2-domain containing) family is known to regulate cell proliferation and organ size via the Hippo signalling pathway. However, the expression level of WWC3 in human tumours and the mechanisms underlying its role in cellular signal transduction have not yet been reported. Herein, we explored the potential roles of WWC3 in lung cancer cells and the corresponding molecular mechanisms. We found low WWC3 expression in both lung cancer cell lines and lung cancer specimens, which was associated with low differentiation, advanced pTNM stage, positive lymph node metastasis, and poor prognosis in patients with lung cancer. Moreover, the overexpression of WWC3 inhibited the proliferation and invasiveness of lung cancer cells. These effects were mediated by the inhibition and stimulation of the Wnt and Hippo pathways, respectively, in vitro and in vivo. Specifically, WWC3 interacts with Dishevelled (Dvl) proteins, prevents casein kinase 1ϵ from phosphorylating Dvls, and inhibits β-catenin nuclear translocation to inhibit the Wnt pathway. Deleting the WW and C-terminal PDZ-binding domains of WWC3 abrogated these effects. Moreover, the interaction of WWC3 with Dvls reduced the interaction between WWC3 and large tumour suppressor 1 (LATS1), as well as decreasing LATS1 phosphorylation to increase the nuclear importation of yes-associated protein (YAP) and attenuate the Hippo pathway. Deleting the WW domain of WWC3 abrogated this effect. These findings demonstrate the molecular interplay between WWC3, Dvls, and LATS1, and reveal a link between the Wnt and Hippo pathways, which provides a potential target for clinical intervention in lung cancer. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  6. Dose specification for hippocampal sparing whole brain radiotherapy (HS WBRT): considerations from the UK HIPPO trial QA programme.

    PubMed

    Megias, Daniel; Phillips, Mark; Clifton-Hadley, Laura; Harron, Elizabeth; Eaton, David J; Sanghera, Paul; Whitfield, Gillian

    2017-03-01

    The HIPPO trial is a UK randomized Phase II trial of hippocampal sparing (HS) vs conventional whole-brain radiotherapy after surgical resection or radiosurgery in patients with favourable prognosis with 1-4 brain metastases. Each participating centre completed a planning benchmark case as part of the dedicated radiotherapy trials quality assurance programme (RTQA), promoting the safe and effective delivery of HS intensity-modulated radiotherapy (IMRT) in a multicentre trial setting. Submitted planning benchmark cases were reviewed using visualization for radiotherapy software (VODCA) evaluating plan quality and compliance in relation to the HIPPO radiotherapy planning and delivery guidelines. Comparison of the planning benchmark data highlighted a plan specified using dose to medium as an outlier by comparison with those specified using dose to water. Further evaluation identified that the reported plan statistics for dose to medium were lower as a result of the dose calculated at regions of PTV inclusive of bony cranium being lower relative to brain. Specification of dose to water or medium remains a source of potential ambiguity and it is essential that as part of a multicentre trial, consideration is given to reported differences, particularly in the presence of bone. Evaluation of planning benchmark data as part of an RTQA programme has highlighted an important feature of HS IMRT dosimetry dependent on dose being specified to water or medium, informing the development and undertaking of HS IMRT as part of the HIPPO trial. Advances in knowledge: The potential clinical impact of differences between dose to medium and dose to water are demonstrated for the first time, in the setting of HS whole-brain radiotherapy.

  7. Stereo photos for evaluating jack pine slash fuels.

    Treesearch

    Richard W. Blank

    1982-01-01

    Describes a quick, visual method for estimating jack pine logging residue and other fuels. The method uses a series of large color photographs and stereo pairs as well as data sheets that detail size classes and loadings of the logging slash and other fuels.

  8. Astronaut Jack Fischer at Rock Creek Park

    NASA Image and Video Library

    2017-11-04

    NASA astronaut Jack Fischer speaks about his time aboard the International Space Station as part of Expeditions 51 and 52, Saturday, Nov. 4, 2017 at the Rock Creek Park Nature Center and Planetarium in Washington, DC. During his 136 day mission aboard the ISS, Fischer conducted two spacewalks and hundreds of scientific experiments. Photo Credit: (NASA/Joel Kowsky)

  9. Jack Polynomials as Fractional Quantum Hall States and the Betti Numbers of the ( k + 1)-Equals Ideal

    NASA Astrophysics Data System (ADS)

    Zamaere, Christine Berkesch; Griffeth, Stephen; Sam, Steven V.

    2014-08-01

    We show that for Jack parameter α = -( k + 1)/( r - 1), certain Jack polynomials studied by Feigin-Jimbo-Miwa-Mukhin vanish to order r when k + 1 of the coordinates coincide. This result was conjectured by Bernevig and Haldane, who proposed that these Jack polynomials are model wavefunctions for fractional quantum Hall states. Special cases of these Jack polynomials include the wavefunctions of Laughlin and Read-Rezayi. In fact, along these lines we prove several vanishing theorems known as clustering properties for Jack polynomials in the mathematical physics literature, special cases of which had previously been conjectured by Bernevig and Haldane. Motivated by the method of proof, which in the case r = 2 identifies the span of the relevant Jack polynomials with the S n -invariant part of a unitary representation of the rational Cherednik algebra, we conjecture that unitary representations of the type A Cherednik algebra have graded minimal free resolutions of Bernstein-Gelfand-Gelfand type; we prove this for the ideal of the ( k + 1)-equals arrangement in the case when the number of coordinates n is at most 2 k + 1. In general, our conjecture predicts the graded S n -equivariant Betti numbers of the ideal of the ( k + 1)-equals arrangement with no restriction on the number of ambient dimensions.

  10. The Jack Wills crowd: towards a sociology of an elite subculture.

    PubMed

    King, Anthony; Smith, Daniel

    2018-03-01

    British sociologists have long been interested in youth sub-cultures. However British sociologists have tended to focus on working class subcultures and avoided engagement with exclusive sub-cultures of elite social groups. This article seeks to attend to this gap by examining the subculture of a British elite: ex-public school students at select universities in the UK in the twenty-first century. This group consists of a relatively small group of young adults, aged between 18 and 23, who attended public schools, especially one of the nine Clarendon schools (Eton, Winchester, Westminster, St. Paul's, Merchant Taylor's, Shrewsbury, Rugby, Harrow and Charterhouse), and were students at a selective group of British universities, primarily Oxford and Cambridge, Durham, Bristol, Exeter, Bath, Manchester, St Andrews and Edinburgh. The article examines the way in which this group has reconfigured and re-constituted itself in the face of globalizing challenges. Specifically, it examines the way in which participation of ex-public school students in events run by and under the patronage of the high street retailing company, Jack Wills, has played a galvanising role for this group in the last decade. The Jack Wills crowd is an example of how some young adults form exclusive social networks and reproduce prevailing forms of privilege. The social networks built around the Jack Wills subculture is likely to provide them with advantages in the job market through a prodigious network of connections and patrons. The Jack Wills subculture potentially contributions to the socio-economic reproduction of the higher professional middle classes. © London School of Economics and Political Science 2017.

  11. Application of metal magnetic memory technology on defects detection of jack-up platform

    NASA Astrophysics Data System (ADS)

    Xu, Changhang; Cheng, Liping; Xie, Jing; Yin, Xiaokang; Chen, Guoming

    2016-02-01

    Metal magnetic memory test (MMMT), which is an effective way in evaluating early damages of ferrimagnets, can determine the existence of material stresses concentration and premature defects. As one of offshore oil exploration and development equipment, jack-up platform always generate stress concentration during its life-cycle due to complicated loading condition and the hash marine environment, which will decline the bearing capacity and cause serious consequences. The paper conducts in situ experiments of defects detection on some key structural components of jack-up platform using MMMT. The signals acquired by MMM-System are processed for feature extraction to evaluate the severity of structure stress concentration. The results show that the method presented in this paper based on MMMT can provide an effective and convenient way of defect detection and structural health monitoring for Jack-up Platform.

  12. Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers

    PubMed Central

    Ricketts, Christopher J.; Wei, Darmood; Yang, Youfeng; Baranes, Sarah M.; Gibbs, Benjamin K.; Ohanjanian, Lernik; Spencer Krane, L.; Scroggins, Bradley T.; Keith Killian, J.; Wei, Ming-Hui; Kijima, Toshiki; Meltzer, Paul S.; Citrin, Deborah E.; Neckers, Len; Vocke, Cathy D.; Marston Linehan, W.

    2018-01-01

    Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15–20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation. The Src family kinase member Yes also regulates YAP1 transcriptional activity. This study investigated the importance of YAP and Yes activity in three NF2-deficient PRCC cell lines. NF2-deficency correlated with increased expression of YAP1 transcriptional targets and siRNA-based knockdown of YAP1 and Yes1 downregulated this pathway and dramatically reduced cell viability. Dasatinib and saracatinib have potent inhibitory effects on Yes and treatment with either resulted in downregulation of YAP1 transcription targets, reduced cell viability, and G0-G1 cell cycle arrest. Xenograft models for NF2-deficient PRCC also demonstrated reduced tumor growth in response to dasatinib. Thus, inhibiting Yes and the subsequent transcriptional activity of YAP1 had a substantial anti-tumor cell effect both in vitro and in vivo and may provide a viable therapeutic approach for patients with NF2-deficient PRCC. PMID:29535838

  13. 3. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 NORTHEAST (BACK) AND SOUTHEAST (SIDE) ELEVATIONS - Franklin Park Zoo, Elephant House, Seaver Street, Boston, Suffolk County, MA

  14. 4. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 SOUTHWEST (FRONT) AND SOUTHEAST (SIDE) ELEVATIONS - Franklin Park Zoo, Elephant House, Seaver Street, Boston, Suffolk County, MA

  15. 2. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 NORTHEAST (BACK) AND NORTHWEST (SIDE) ELEVATIONS - Franklin Park Zoo, Elephant House, Seaver Street, Boston, Suffolk County, MA

  16. 1. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 SOUTHWEST (FRONT) AND NORTHWEST (SIDE) ELEVATIONS - Franklin Park Zoo, Elephant House, Seaver Street, Boston, Suffolk County, MA

  17. 3. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 NORTHEAST (BACK) AND NORTHWEST (SIDE) ELEVATION - Franklin Park Zoo, Feline House, Seaver Street, Boston, Suffolk County, MA

  18. 2. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 SOUTHWEST (FRONT) AND NORTHWEST (SIDE) ELEVATION - Franklin Park Zoo, Feline House, Seaver Street, Boston, Suffolk County, MA

  19. 1. Historic American Buildings Survey Jack Maley, Photographer May 31, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey Jack Maley, Photographer May 31, 1978 SOUTHWEST (FRONT) AND SOUTHEAST (SIDE) ELEVATION - Franklin Park Zoo, Feline House, Seaver Street, Boston, Suffolk County, MA

  20. Sphaeropsis Collar Rot of Red and Jack Pines

    Treesearch

    Glen Stanosz; Linda Haugen; Joseph O' Brien

    2002-01-01

    Sphaeropsis collar rot has been detected in red and jack pines in Wisconsin and Michigan, and it could be affecting pines in other states. This disease may be less familiar than Sphaeropsis shoot blight, but both the incidence and the distribution of collar rot appear to be increasing.

  1. 5. 3/4 view looking southwest. Jack Boucher, photographer, 1977 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. 3/4 view looking southwest. Jack Boucher, photographer, 1977 - Neshanic Station Lenticular Truss Bridge, State Route 567, spanning South Branch of Raritan River, Neshanic Station, Somerset County, NJ

  2. 'Weightless' acrylic painting by Jack Kroehnke

    NASA Technical Reports Server (NTRS)

    1987-01-01

    'Weightless' acrylic painting by Jack Kroehnke depicts STS-26 Discovery, Orbiter Vehicle (OV) 103, Mission Specialist (MS) David C. Hilmers participating in extravehicular activity (EVA) simulation in JSC Weightless Environment Training Facility (WETF) Bldg 29. In the payload bay (PLB) mockup, Hilmers, wearing extravehicular mobility unit (EMU), holds onto the mission-peculiar equipment support structure in foreground while SCUBA-equipped diver monitors activity overhead and camera operator records EVA procedures. Copyrighted art work for use by NASA.

  3. Evaluation of the airborne quantum cascade laser spectrometer (QCLS) measurements of the carbon and greenhouse gas suite - CO2, CH4, N2O, and CO - during the CalNex and HIPPO campaigns

    NASA Astrophysics Data System (ADS)

    Santoni, G. W.; Daube, B. C.; Kort, E. A.; Jiménez, R.; Park, S.; Pittman, J. V.; Gottlieb, E.; Xiang, B.; Zahniser, M. S.; Nelson, D. D.; McManus, J. B.; Peischl, J.; Ryerson, T. B.; Holloway, J. S.; Andrews, A. E.; Sweeney, C.; Hall, B.; Hintsa, E. J.; Moore, F. L.; Elkins, J. W.; Hurst, D. F.; Stephens, B. B.; Bent, J.; Wofsy, S. C.

    2014-06-01

    We present an evaluation of aircraft observations of the carbon and greenhouse gases CO2, CH4, N2O, and CO using a direct-absorption pulsed quantum cascade laser spectrometer (QCLS) operated during the HIPPO and CalNex airborne experiments. The QCLS made continuous 1 Hz measurements with 1σ Allan precisions of 20, 0.5, 0.09, and 0.15 ppb for CO2, CH4, N2O, and CO, respectively, over > 500 flight hours on 79 research flights. The QCLS measurements are compared to two vacuum ultraviolet (VUV) CO instruments (CalNex and HIPPO), a cavity ring-down spectrometer (CRDS) measuring CO2 and CH4 (CalNex), two broadband non-dispersive infrared (NDIR) spectrometers measuring CO2 (HIPPO), two onboard gas chromatographs measuring a variety of chemical species including CH4, N2O, and CO (HIPPO), and various flask-based measurements of all four species. QCLS measurements are tied to NOAA and WMO standards using an in-flight calibration system, and mean differences when compared to NOAA CCG flask data over the 59 HIPPO research flights were 100, 1, 1, and 2 ppb for CO2, CH4, N2O, and CO, respectively. The details of the end-to-end calibration procedures and the data quality assurance and quality control (QA/QC) are presented. Specifically, we discuss our practices for the traceability of standards given uncertainties in calibration cylinders, isotopic and surface effects for the long-lived greenhouse gas tracers, interpolation techniques for in-flight calibrations, and the effects of instrument linearity on retrieved mole fractions.

  4. Do Jack Hills Detrital Zircons Contain Records of the Early Geodynamo?

    NASA Astrophysics Data System (ADS)

    Weiss, B. P.; Maloof, A. C.; Tailby, N. D.; Ramezani, J.; Fu, R. R.; Glenn, D. R.; Kehayias, P.; Walsworth, R. L.; Hanus, V.; Trail, D.; Watson, E. B.; Harrison, T. M.; Bowring, S. A.; Kirschvink, J. L.; Swanson-Hysell, N.; Coe, R. S.; Einsle, J. F.; Harrison, R. J.

    2015-12-01

    It is unknown when Earth's dynamo magnetic field originated. With crystallization ages ranging from 3.0-4.38 Ga, detrital zircon crystals found in the Jack Hills of Western Australia might preserve a record of the missing first billion years of Earth's magnetic field history. Recently, Tarduno et al. (2015) argued that magnetization in Jack Hills zircons provides evidence for a substantial geomagnetic field dating back to their U/Pb formation ages (3.3 and 4.2 Ga). However, the identification of such ancient field records requires establishing that the zircons have avoided remagnetization since their formation. At a minimum, it should be demonstrated that they have not been remagnetized since being deposited at ~3.0 Ga. To establish the timing and intensity of the metamorphic and alteration events experienced by the zircon, we conducted 12 paleomagnetic field tests in combination with U-Pb geochronology on their host rocks (see Weiss et al. 2015, EPSL). Our data show that the Hadean zircon-bearing rocks and surrounding region have been pervasively remagnetized, with the final major overprinting likely from emplacement of the Warakurna large igneous province at 1.1 Ga (see Figure). Even if some Jack Hills zircons do record a pre-depositional magnetization, they still could have been remagnetized sometime during the 1.4 Gy between their crystallization and their deposition. First, the temperatures capable of remagnetizing magnetite inclusions are well below those that could reset a U-Pb date or result in significant discordance. Therefore, thermal events capable of completely remagnetizing Jack Hills zircons could be undetected by the techniques reported by Tarduno at al. (2015). Second, the zircons' magnetization might be dominated by secondary ferromagnetic inclusions or contamination. To address the latter possibility, we are conducting electron microscopy, x-ray tomography, and magnetic field mapping on the zircons. Our initial quantum diamond magnetometry high

  5. 20. Jack E. Boucher, Photogtapher, May 1974. CLOSEUP VIEW OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Jack E. Boucher, Photogtapher, May 1974. CLOSE-UP VIEW OF PAULI-LENTICULAR TRUSS SYSTEM, CENTRAL AREA. - Smithfield Street Bridge, Spanning Monongahela River on Smithfield Street, Pittsburgh, Allegheny County, PA

  6. 7. Straighton view of east portal. Jack Boucher, photographer, 1977 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Straight-on view of east portal. Jack Boucher, photographer, 1977 - Neshanic Station Lenticular Truss Bridge, State Route 567, spanning South Branch of Raritan River, Neshanic Station, Somerset County, NJ

  7. 9. View looking east down cantilevered walkway. Jack Boucher, photographer, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. View looking east down cantilevered walkway. Jack Boucher, photographer, 1977 - Neshanic Station Lenticular Truss Bridge, State Route 567, spanning South Branch of Raritan River, Neshanic Station, Somerset County, NJ

  8. Jack Reeves and his science.

    PubMed

    Moore, Lorna G; Grover, Robert F

    2006-04-28

    John T. (Jack) Reeves' science is reviewed across the 37 years of his research career at the University of Colorado Health Sciences Center, a period which occupied approximately half his remarkable life. His contributions centered on understanding the inter-relatedness as well as the underlying mechanisms controlling the various components of the O(2) transport system. We review here his studies on exercise performance; these encompassed about half his scientific output with the other half being devoted to the study of hypoxic pulmonary hypertension. Early studies concerned cardiac output, showing how it was a balance between O(2) uptake and O(2) extraction, and that cardiac output during exercise at high altitude was reduced, most likely because of decreased plasma volume and left ventricular filling. Jack's many studies addressed virtually every aspect of the O(2) transport system -- adding significantly to our understanding of the syndromes of altitude illness, the mechanisms by which ventilatory sensitivity to hypoxia and hypercapnia influenced ventilatory acclimatization, and the contributions of the various limbs of the autonomic nervous system on systemic blood pressure, vascular resistance and substrate utilization. His scientific career ended abruptly in 2004 when struck by a car while biking to work, but his legacy remains in his more than 385+ research articles or chapters, the 40+ fellows he trained, and the countless number of younger (and older) scientists for whom he served as a role model for learning how to scrutinize their data and present their findings in clear and sometimes bold prose. An integral man, he is sorely missed.

  9. 2. EAST SIDE OF SLAVE QUARTERS (Jack E. Boucher, photgrapher, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. EAST SIDE OF SLAVE QUARTERS (Jack E. Boucher, photgrapher, April/May, 1986) - Felix & Odile Pratt Valle Slave Quarters, Southeast corner of Merchant & Second Streets, Sainte Genevieve, Ste. Genevieve County, MO

  10. 19. Jack E, Boucher, Photographer, May 1974. CLOSEUP DETAIL VIEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    19. Jack E, Boucher, Photographer, May 1974. CLOSE-UP DETAIL VIEW OF PAULI-LENTICULAR TRUSS SYSTEM, CENTRAL AREA. - Smithfield Street Bridge, Spanning Monongahela River on Smithfield Street, Pittsburgh, Allegheny County, PA

  11. 4. View looking north showing bridge in elevation. Jack Boucher, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. View looking north showing bridge in elevation. Jack Boucher, photographer, 1977 - Neshanic Station Lenticular Truss Bridge, State Route 567, spanning South Branch of Raritan River, Neshanic Station, Somerset County, NJ

  12. 21 CFR 133.153 - Monterey cheese and monterey jack cheese.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... a lactic acid-producing bacterial culture. One or more of the clotting enzymes specified in... “monterey cheese” or alternatively, “monterey jack cheese”. (d) Label declaration. Each of the ingredients...

  13. 21 CFR 133.153 - Monterey cheese and monterey jack cheese.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... a lactic acid-producing bacterial culture. One or more of the clotting enzymes specified in... “monterey cheese” or alternatively, “monterey jack cheese”. (d) Label declaration. Each of the ingredients...

  14. 21 CFR 133.153 - Monterey cheese and monterey jack cheese.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a lactic acid-producing bacterial culture. One or more of the clotting enzymes specified in... “monterey cheese” or alternatively, “monterey jack cheese”. (d) Label declaration. Each of the ingredients...

  15. JACK CREEK BASIN, MONTANA.

    USGS Publications Warehouse

    Kiilsgaard, Thor H.; Van Noy, Ronald M.

    1984-01-01

    A mineral survey of the Jack Creek basin area in Montana revealed that phosphate rock underlies the basin. The phosphate rock is in thin beds that dip steeply and are broken and offset by faults. These features plus the rugged topography of the region would make mining difficult; however, this study finds the area to have a probable mineral-resource potential for phosphate. Sedimentary rock formations favorable for oil and gas also underlie the basin. No oil or gas has been produced from the basin or from nearby areas in southwestern Montana, but oil and gas have been produced from the same favorable formations elsewhere in Montana. The possibility of oil and gas being produced from the basin is slight but it cannot be ignored.

  16. Prediction methods of spudcan penetration for jack-up units

    NASA Astrophysics Data System (ADS)

    Zhang, Ai-xia; Duan, Meng-lan; Li, Hai-ming; Zhao, Jun; Wang, Jian-jun

    2012-12-01

    Jack-up units are extensively playing a successful role in drilling engineering around the world, and their safety and efficiency take more and more attraction in both research and engineering practice. An accurate prediction of the spudcan penetration depth is quite instrumental in deciding on whether a jack-up unit is feasible to operate at the site. The prediction of a too large penetration depth may lead to the hesitation or even rejection of a site due to potential difficulties in the subsequent extraction process; the same is true of a too small depth prediction due to the problem of possible instability during operation. However, a deviation between predictive results and final field data usually exists, especially when a strong-over-soft soil is included in the strata. The ultimate decision sometimes to a great extent depends on the practical experience, not the predictive results given by the guideline. It is somewhat risky, but no choice. Therefore, a feasible predictive method for the spudcan penetration depth, especially in strata with strong-over-soft soil profile, is urgently needed by the jack-up industry. In view of this, a comprehensive investigation on methods of predicting spudcan penetration is executed. For types of different soil profiles, predictive methods for spudcan penetration depth are proposed, and the corresponding experiment is also conducted to validate these methods. In addition, to further verify the feasibility of the proposed methods, a practical engineering case encountered in the South China Sea is also presented, and the corresponding numerical and experimental results are also presented and discussed.

  17. Impacts of updated spectroscopy on thermal infrared retrievals of methane evaluated with HIPPO data

    NASA Astrophysics Data System (ADS)

    Alvarado, M. J.; Payne, V. H.; Cady-Pereira, K. E.; Hegarty, J. D.; Kulawik, S. S.; Wecht, K. J.; Worden, J. R.; Pittman, J. V.; Wofsy, S. C.

    2015-02-01

    Errors in the spectroscopic parameters used in the forward radiative transfer model can introduce spatially, temporally, and altitude-dependent biases in trace gas retrievals. For well-mixed trace gases such as methane, where the variability of tropospheric mixing ratios is relatively small, reducing such biases is particularly important. We use aircraft observations from all five missions of the HIAPER Pole-to-Pole Observations (HIPPO) of the Carbon Cycle and Greenhouse Gases Study to evaluate the impact of updates to spectroscopic parameters for methane (CH4), water vapor (H2O), and nitrous oxide (N2O) on thermal infrared retrievals of methane from the NASA Aura Tropospheric Emission Spectrometer (TES). We find that updates to the spectroscopic parameters for CH4 result in a substantially smaller mean bias in the retrieved CH4 when compared with HIPPO observations. After an N2O-based correction, the bias in TES methane upper tropospheric representative values for measurements between 50° S and 50° N decreases from 56.9 to 25.7 ppbv, while the bias in the lower tropospheric representative value increases only slightly (from 27.3 to 28.4 ppbv). For retrievals with less than 1.6 degrees of freedom for signal (DOFS), the bias is reduced from 26.8 to 4.8 ppbv. We also find that updates to the spectroscopic parameters for N2O reduce the errors in the retrieved N2O profile.

  18. Impacts of updated spectroscopy on thermal infrared retrievals of methane evaluated with HIPPO data

    NASA Astrophysics Data System (ADS)

    Alvarado, M. J.; Payne, V. H.; Cady-Pereira, K. E.; Hegarty, J. D.; Kulawik, S. S.; Wecht, K. J.; Worden, J. R.; Pittman, J. V.; Wofsy, S. C.

    2014-09-01

    Errors in the spectroscopic parameters used in the forward radiative transfer model can introduce altitude-, spatially-, and temporally-dependent biases in trace gas retrievals. For well-mixed trace gases such as methane, where the variability of tropospheric mixing ratios is relatively small, reducing such biases is particularly important. We use aircraft observations from all five missions of the HIAPER Pole-to-Pole Observations (HIPPO) of the Carbon Cycle and Greenhouse Gases Study to evaluate the impact of updates to spectroscopic parameters for methane (CH4), water vapor (H2O), and nitrous oxide (N2O) on thermal infrared retrievals of methane from the NASA Aura Tropospheric Emission Spectrometer (TES). We find that updates to the spectroscopic parameters for CH4 result in a substantially smaller mean bias in the retrieved CH4 when compared with HIPPO observations. After an N2O-based correction, the bias in TES methane upper tropospheric representative values for measurements between 50° S and 50° N decreases from 56.9 to 25.7 ppbv, while the bias in the lower tropospheric representative value increases only slightly (from 27.3 to 28.4 ppbv). For retrievals with less than 1.6 DOFS, the bias is reduced from 26.8 to 4.8 ppbv. We also find that updates to the spectroscopic parameters for N2O reduce the errors in the retrieved N2O profile.

  19. Geographic variation of jack pine (Pinus banksiana Lamb.)

    Treesearch

    Jung Oh Hyun

    1977-01-01

    Ten traits were measured on 10-year-old jack pine grown at Cloquet, Minnesota, from seed collected from 90 provenances. The traits were examined by using analysis of variance and computing correlations for all combinations of 9 traits plus latitude , longitude, and elevation of the seed sources and cluster analyses using the D2 values from the...

  20. Jack Colby Continues Stellar Legacy of APPA Fellows

    ERIC Educational Resources Information Center

    Thaler-Carter, Ruth E.

    2011-01-01

    This article profiles 2011 APPA Fellow Jack K. Colby, assistant vice chancellor for facilities operations at North Carolina State University. Colby has a history of nonstop service to his profession and to APPA that makes that ever-active, never-stop rabbit look like a piker. Like previous APPA Fellows, Colby could easily rest on his laurels of…

  1. Seismic analysis of the frame structure reformed by cutting off column and jacking based on stiffness ratio

    NASA Astrophysics Data System (ADS)

    Zhao, J. K.; Xu, X. S.

    2017-11-01

    The cutting off column and jacking technology is a method for increasing story height, which has been widely used and paid much attention in engineering. The stiffness will be changed after the process of cutting off column and jacking, which directly affects the overall seismic performance. It is usually necessary to take seismic strengthening measures to enhance the stiffness. A five story frame structure jacking project in Jinan High-tech Zone was taken as an example, and three finite element models were established which contains the frame model before lifting, after lifting and after strengthening. Based on the stiffness, the dynamic time-history analysis was carried out to research its seismic performance under the EL-Centro seismic wave, the Taft seismic wave and the Tianjin artificial seismic wave. The research can provide some guidance for the design and construction of the entire jack lifting structure.

  2. Investigating the Jack the Ripper Case: Engaging Students in a Criminal Investigations Class through Active Learning

    ERIC Educational Resources Information Center

    Gutierrez, Daniel; Kazmi, Syed

    2010-01-01

    The present study examines the utilization of a class project involving the Jack the Ripper murders. Students enrolled in a criminal investigations class were required to investigate the five canonical murders associated with the infamous serial killer known as Jack the Ripper and the murders that occurred in London during 1888. This paper…

  3. Jack Michael's Musings on the 60th Anniversary of Skinner's "Verbal Behavior"

    ERIC Educational Resources Information Center

    Esch, Barbara E.; Esch, John W.; Palmer, David C.

    2017-01-01

    When the B. F. Skinner Foundation reprinted Skinner's "Verbal Behavior" in 1992, Jack Michael wrote one of its two forewords, a detailed outline of the book's purpose and scope. On the 60th anniversary of the first publication (1957) of "Verbal Behavior", Jack reflects on the book's impact and its importance to the…

  4. Manager's handbook for jack pine in the north central states.

    Treesearch

    John W. Benzie

    1977-01-01

    Provides a key for the resource manager to use in choosing silvicultural practices for the management of jack pine. Control of stand composition, growth, and stand establishment for timber production, water, wildlife, and recreation are discussed.

  5. Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

    PubMed

    Liu, Bo; Sun, Li-Hua; Huang, Yan-Fei; Guo, Li-Jun; Luo, Li-Shu

    2018-02-01

    Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Determining the effect of different cooking methods on the nutritional composition of salmon (Salmo salar) and chilean jack mackerel (Trachurus murphyi) fillets.

    PubMed

    Bastías, José M; Balladares, Pamela; Acuña, Sergio; Quevedo, Roberto; Muñoz, Ociel

    2017-01-01

    The effect of four cooking methods was evaluated for proximate composition, fatty acid, calcium, iron, and zinc content in salmon and Chilean jack mackerel. The moisture content of steamed salmon decreased (64.94%) compared to the control (68.05%); a significant decrease was observed in Chilean jack mackerel in all the treatments when compared to the control (75.37%). Protein content in both salmon and Chilean jack mackerel significantly increased under the different treatments while the most significant decrease in lipids was found in oven cooking and canning for salmon and microwaving for Chilean jack mackerel. Ash concentration in both salmon and Chilean jack mackerel did not reveal any significant differences. Iron and calcium content only had significant changes in steaming while zinc did not undergo any significant changes in the different treatments. Finally, no drastic changes were observed in the fatty acid profile in both salmon and Chilean jack mackerel.

  7. HOW to Identify and Control Stem Rusts of Jack Pine

    Treesearch

    Kathryn Robbins; Dale K. Smeltzer; D. W. French

    Damage to jack pine caused by rust fungi includes growth reduction, cankers, death (by girdling or wind breakage), and creation of entryways for other fungi and insects. Seedlings and saplings are more seriously affected than older trees.

  8. Is the lateral jack-knife position responsible for cases of transient neurapraxia?

    PubMed

    Molinares, Diana Margarita; Davis, Timothy T; Fung, Daniel A; Liu, John Chung-Liang; Clark, Stephen; Daily, David; Mok, James M

    2016-01-01

    The lateral jack-knife position is often used during transpsoas surgery to improve access to the spine. Postoperative neurological signs and symptoms are very common after such procedures, and the mechanism is not adequately understood. The objective of this study is to assess if the lateral jack-knife position alone can cause neurapraxia. This study compares neurological status at baseline and after positioning in the 25° right lateral jack-knife (RLJK) and the right lateral decubitus (RLD) position. Fifty healthy volunteers, ages 21 to 35, were randomly assigned to one of 2 groups: Group A (RLD) and Group B (RLJK). Motor and sensory testing was performed prior to positioning. Subjects were placed in the RLD or RLJK position, according to group assignment, for 60 minutes. Motor testing was performed immediately after this 60-minute period and again 60 minutes thereafter. Sensory testing was performed immediately after the 60-minute period and every 15 minutes thereafter, for a total of 5 times. Motor testing was performed by a physical therapist who was blinded to group assignment. A follow-up call was made 7 days after the positioning sessions. Motor deficits were observed in the nondependent lower limb in 100% of the subjects in Group B, and no motor deficits were seen in Group A. Statistically significant differences (p < 0.05) were found between the 2 groups with respect to the performance on the 10-repetition maximum test immediately immediately and 60 minutes after positioning. Subjects in Group B had a 10%-70% (average 34.8%) decrease in knee extension strength and 20%-80% (average 43%) decrease in hip flexion strength in the nondependent limb. Sensory abnormalities were observed in the nondependent lower limb in 98% of the subjects in Group B. Thirty-six percent of the Group B subjects still exhibited sensory deficits after the 60-minute recovery period. No symptoms were reported by any subject during the follow-up calls 7 days after positioning. Twenty

  9. The late Quaternary history of lodgepole and jack pines

    Treesearch

    William B. Critchfield

    1985-01-01

    Lodgepole and jack pines (Pinus contorta Dougl. ex. Loud, and Pinus banksiana Lamb.), components of the North American boreal forest, have pioneering roles after major disturbances such as fire or glaciation. These species are closely related and hybridize in western Canada, but their fossil records and contemporary variation...

  10. Filling Holes with Words: An Interview with Jack Gantos.

    ERIC Educational Resources Information Center

    Shoemaker, Joel

    2003-01-01

    This interview with Jack Gantos, an author who writes books for young adults, focuses on how he uses his own personal experiences in his books. Discusses memories of his father and his childhood, drug-smuggling activities and the resulting jail time, and student reactions to his books. (LRW)

  11. The Bildungsroman Tradition: The Philosophical Maturation of Jack Burden in "All The King's Men"

    ERIC Educational Resources Information Center

    Al-Shraah, Bassam M.

    2017-01-01

    This paper aims to sketch out the transformation that Jack Burden--the main character in the novel--had gone through. With all the political leanings in Warren's "All the king's Men," Jack Burden seems to have had developed his own theories of dealing with life and people all through his life. He has always suffered an inferiority…

  12. Determining the effect of different cooking methods on the nutritional composition of salmon (Salmo salar) and chilean jack mackerel (Trachurus murphyi) fillets

    PubMed Central

    Balladares, Pamela; Acuña, Sergio; Quevedo, Roberto; Muñoz, Ociel

    2017-01-01

    The effect of four cooking methods was evaluated for proximate composition, fatty acid, calcium, iron, and zinc content in salmon and Chilean jack mackerel. The moisture content of steamed salmon decreased (64.94%) compared to the control (68.05%); a significant decrease was observed in Chilean jack mackerel in all the treatments when compared to the control (75.37%). Protein content in both salmon and Chilean jack mackerel significantly increased under the different treatments while the most significant decrease in lipids was found in oven cooking and canning for salmon and microwaving for Chilean jack mackerel. Ash concentration in both salmon and Chilean jack mackerel did not reveal any significant differences. Iron and calcium content only had significant changes in steaming while zinc did not undergo any significant changes in the different treatments. Finally, no drastic changes were observed in the fatty acid profile in both salmon and Chilean jack mackerel. PMID:28686742

  13. Ten-year height growth variation in Lake States jack pine

    Treesearch

    James P. King

    1966-01-01

    Jack pine (Pinus banksiana Lamb.) is one of the major pulpwood producing species in the Lake States. It is found on a variety of sites, but its outstanding characteristic is its ability to make early rapid growth on dry sandy soils.

  14. Structure and biomass production of one- to seven-year-old intensively cultured jack pine plantation in Wisconsin.

    Treesearch

    J. Zavitkovski; David H. Dawson

    1978-01-01

    Spacing and rotation length effects were studied for 7 years in intensively cultured jack pine stands. Production culminated at age 5 in the densest planting and progressively later in more open spacing. Biomass production was two to several times higher than in jack pine plantations grown under traditional silvicultural systems.

  15. microRNA 31 functions as an endometrial cancer oncogene by suppressing Hippo tumor suppressor pathway

    PubMed Central

    2014-01-01

    Background We aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype. Methods We investigated the growth potentials of MIR31-overexpressing HEC-50B cells in vitro and in vivo. In order to identify the target molecule of MIR31, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human endometrial cancer tissues. We also investigated the MIR31 expression in 34 patients according to the postoperative risk of recurrence. Results The overexpression of MIR31 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3’-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of CCND1. Furthermore, the expression levels of MIR31 were significantly increased (10.7-fold) in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival. Conclusions MIR31 functions as an oncogene in endometrial cancer by repressing the Hippo pathway. MIR31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer. PMID:24779718

  16. The Atmospheric Distribution of Molecular Hydrogen (H2) and Related Species During HIPPO and Other Recent Airborne Missions

    NASA Astrophysics Data System (ADS)

    Hintsa, E. J.; Moore, F. L.; Dutton, G. S.; Hall, B. D.; Nance, J. D.; Hurst, D. F.; Novelli, P. C.; Elkins, J. W.; Daube, B.; Kort, E. A.; Pittman, J. V.; Santoni, G. W.; Wofsy, S. C.; Jaegle, L.

    2012-12-01

    The goal of the HIAPER Pole-to-Pole Observations (HIPPO) of Carbon Cycle and Greenhouse Gases Study was to measure a large set of trace gases and aerosols as a function of altitude and latitude in different seasons in order to better understand their sources, sinks, and atmospheric transport, and to use these measurements to compare with a variety of chemical transport models, ultimately leading to improvements in the models. The NSF/NCAR Gulfstream V (GV) aircraft (formerly known as HIAPER) was equipped with instruments for trace gases, aerosols, and meteorological parameters, and flew a set of five transects in 2009-2011 from Colorado, to Anchorage, AK, to near the North Pole, then south to Christchurch, NZ, toward the edge of Antarctica, and back to the northern hemisphere high latitudes, with intermediate stops at different locations in the Pacific Ocean. On each leg of the journey, the GV carried out a series of profiles from the marine (or continental) boundary layer to the stratosphere, generating a set of altitude/latitude slices of the atmosphere in different seasons (January 2009, October-November 2009, March-April 2010, June-July 2011, and August-September 2011). While HIPPO was in progress, data were also obtained at higher altitudes in the stratosphere over the Pacific Ocean from the NASA Global Hawk aircraft during the GloPac (Global Hawk Pacific; March-April 2010) and ATTREX (Airborne Tropical Tropopause Experiment; October-November 2011) missions, respectively. In this presentation, results are shown that were obtained from the UCATS and PANTHER instruments and other sensors on board the GV and the Global Hawk. UCATS (the UAS Chromatograph for Atmospheric Trace Species) flew on both platforms and was configured to measure N2O, SF6, H2, CH4, CO, water vapor, and ozone. PANTHER (PAN and other Trace Hydrohalocarbon ExpeRiment) measures an even larger set of trace gases with gas chromatography and a mass spectrometer, and flew on every leg of HIPPO. The

  17. Teaching Scientists to Fish, as Inspired by Jack Dymond

    NASA Astrophysics Data System (ADS)

    Franks, S. E.

    2004-12-01

    It is almost inconceivable that as Jack Dymond's graduate student for eight years, I never mastered the skill of fly-fishing, a pursuit so near and dear to his heart. In fact, Jack did inspire me, not to tie flies and cast, but eventually to teach fellow scientists to fish. The work I'll present - connecting scientists and educators to achieve societal benefit - is profoundly influenced by Jack's dedication to applying scientific understanding and critical thinking to societal issues. With colleagues in the Centers for Ocean Sciences Education Excellence (COSEE), http://www.cosee.net/, I enable scientists to efficiently make meaningful contributions to educational outreach. A key goal of the multi-Center, national COSEE Network is helping scientists build the skills and acquire the resources needed to share their science with diverse audiences. At Scripps, we are piloting an innovative approach to helping scientists meet funding agencies' broader impact requirements. Key elements of the approach include: 1) services to identify educational outreach options that best fit scientists' research and preferences; 2) assistance establishing partnerships with educational outreach providers who have the skills and resources to develop and implement effective programs and exhibits; and 3) nuts and bolts (line and fly) assistance writing proposal text, drafting budgets, and coordinating with institutional business offices to ensure that the proposed educational outreach effort is compelling and sufficiently funded. Where does the fishing lesson come in? We facilitators of scientist-educator partnerships empower scientists to launch enduring collaborations. Once comfortable working with top-notch educational organizations, scientists can tap these resources, project after project, often with little or no additional involvement on our part. Our initial investment in brokering the relationships is richly rewarded. By helping scientists get started, it's as if we are teaching

  18. 14 CFR 25.519 - Jacking and tie-down provisions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... structure must be designed for a vertical load of 1.33 times the vertical static reaction at each jacking point acting singly and in combination with a horizontal load of 0.33 times the vertical static reaction...: (i) The airplane structure must be designed for a vertical load of 1.33 times the vertical reaction...

  19. 14 CFR 25.519 - Jacking and tie-down provisions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... structure must be designed for a vertical load of 1.33 times the vertical static reaction at each jacking point acting singly and in combination with a horizontal load of 0.33 times the vertical static reaction...: (i) The airplane structure must be designed for a vertical load of 1.33 times the vertical reaction...

  20. 14 CFR 25.519 - Jacking and tie-down provisions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... structure must be designed for a vertical load of 1.33 times the vertical static reaction at each jacking point acting singly and in combination with a horizontal load of 0.33 times the vertical static reaction...: (i) The airplane structure must be designed for a vertical load of 1.33 times the vertical reaction...

  1. 14 CFR 25.519 - Jacking and tie-down provisions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... structure must be designed for a vertical load of 1.33 times the vertical static reaction at each jacking point acting singly and in combination with a horizontal load of 0.33 times the vertical static reaction...: (i) The airplane structure must be designed for a vertical load of 1.33 times the vertical reaction...

  2. 14 CFR 25.519 - Jacking and tie-down provisions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... structure must be designed for a vertical load of 1.33 times the vertical static reaction at each jacking point acting singly and in combination with a horizontal load of 0.33 times the vertical static reaction...: (i) The airplane structure must be designed for a vertical load of 1.33 times the vertical reaction...

  3. 29 CFR 1926.305 - Jacks-lever and ratchet, screw, and hydraulic.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Tools-Hand and... of slippage of the metal cap of the jack, a wood block shall be placed between the cap and the load...

  4. Nematode infection in fish from Cartagena Bay, North of Colombia.

    PubMed

    Verbel, Jesús Olivero; Caballero-Gallardo, Karina; Arroyo-Salgado, Bárbara

    2011-04-19

    Parasitic nematode infection indices were recorded in different fish species collected at Cartagena Bay, North of Colombia. Among 19 studied species, the Mugil genus presented the highest prevalence (83.9-100%), although Sciades herzbergii, Caranx hippos and Centropomus undecimalis were also found infected with nematodes. Parasites were found in the liver, intestinal mesenteries and encysted near the intervertebral joints, with an average parasite abundance of 4.0 ± 0.3 nematodes per fish. Morphological analysis allowed the identification of these nematodes as Contracaecum sp. A small, but positive correlation was found between parasite abundance and length (R=0.294, P<0.001) and weight (R=0.244, P<0.001). In contrast, the correlation between parasite abundance and condition factor was negative (R=-0.191, P<0.001). These results are the first describing the presence of nematodes in several fish species of this ecosystem, and it highlights the need for monitoring parasitism in Mugil species in order to avoid parasite ingestion during fish consumption. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Developing Political Activism Awareness: An Interview with Jack Trammell

    ERIC Educational Resources Information Center

    Shetron, Tamara Harper

    2013-01-01

    This article presents an interview with Jack Trammell, whose contributions in the field of education have encompassed a variety of areas with one common denominator: equal access to higher education for all. He serves as the director of Disability Support Services at Randolph-Macon College in Ashland, Va, where he is also an assistant professor,…

  6. Jack Pine and Aspen Forest Floors in Northeastern Minnesota

    Treesearch

    Robert M. Loomis

    1977-01-01

    Characteristics of upland forest floors under mature jack pine and aspen in northeastern Minnesota were investigated. These fuel measurements were needed as inputs for fire behavior prediction models -- useful for fire management decisions. The forest floor weight averaged 33,955 kg/ha and depth averaged 7.1 cm. Bulk density averaged 17 kg/m3 for the L (litter)...

  7. Astronaut Jack Fischer at Air and Space Museum

    NASA Image and Video Library

    2017-11-03

    NASA astronaut Jack Fischer conducts an experiment during a Stem in 30 segment, Friday, Nov. 3, 2017 at Smithsonian's National Air and Space Museum in Washington. During Expedition 52, Fischer completed hundreds of scientific experiments and two spacewalks, and concluded his 136-day mission onboard the International Space Station, when he landed in a remote area near the town of Zhezkazgan, Kazakhstan in September 2017. Photo Credit: (NASA/Aubrey Gemignani)

  8. Astronaut Jack Fischer at Air and Space Museum

    NASA Image and Video Library

    2017-11-03

    NASA astronaut Jack Fischer speaks about his time onboard the International Space Station (ISS) during Expeditions 51/52, Friday, Nov. 3, 2017 at Smithsonian's National Air and Space Museum in Washington. During Expedition 52, Fischer completed hundreds of scientific experiments and two spacewalks, and concluded his 136-day mission when he landed in a remote area near the town of Zhezkazgan, Kazakhstan in September 2017. Photo Credit: (NASA/Aubrey Gemignani)

  9. 9. Historic American Buildings Survey; Jack E. Boucher, photographer; Sept. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. Historic American Buildings Survey; Jack E. Boucher, photographer; Sept. 1969 Copy of measured drawing, 1st floor plan, 1925 (From file of Wash. D.C. Board of Education, office of buildings and grounds) - Jackson (Public) School, R Street & Avon Place Northwest, Washington, District of Columbia, DC

  10. Variation of Time Domain Failure Probabilities of Jack-up with Wave Return Periods

    NASA Astrophysics Data System (ADS)

    Idris, Ahmad; Harahap, Indra S. H.; Ali, Montassir Osman Ahmed

    2018-04-01

    This study evaluated failure probabilities of jack up units on the framework of time dependent reliability analysis using uncertainty from different sea states representing different return period of the design wave. Surface elevation for each sea state was represented by Karhunen-Loeve expansion method using the eigenfunctions of prolate spheroidal wave functions in order to obtain the wave load. The stochastic wave load was propagated on a simplified jack up model developed in commercial software to obtain the structural response due to the wave loading. Analysis of the stochastic response to determine the failure probability in excessive deck displacement in the framework of time dependent reliability analysis was performed by developing Matlab codes in a personal computer. Results from the study indicated that the failure probability increases with increase in the severity of the sea state representing a longer return period. Although the results obtained are in agreement with the results of a study of similar jack up model using time independent method at higher values of maximum allowable deck displacement, it is in contrast at lower values of the criteria where the study reported that failure probability decreases with increase in the severity of the sea state.

  11. Modeling of the jack rabbit series of experiments with a temperature based reactive burn model

    NASA Astrophysics Data System (ADS)

    Desbiens, Nicolas

    2017-01-01

    The Jack Rabbit experiments, performed by Lawrence Livermore National Laboratory, focus on detonation wave corner turning and shock desensitization. Indeed, while important for safety or charge design, the behaviour of explosives in these regimes is poorly understood. In this paper, our temperature based reactive burn model is calibrated for LX-17 and compared to the Jack Rabbit data. It is shown that our model can reproduce the corner turning and shock desensitization behaviour of four out of the five experiments.

  12. JackIn Head: Immersive Visual Telepresence System with Omnidirectional Wearable Camera.

    PubMed

    Kasahara, Shunichi; Nagai, Shohei; Rekimoto, Jun

    2017-03-01

    Sharing one's own immersive experience over the Internet is one of the ultimate goals of telepresence technology. In this paper, we present JackIn Head, a visual telepresence system featuring an omnidirectional wearable camera with image motion stabilization. Spherical omnidirectional video footage taken around the head of a local user is stabilized and then broadcast to others, allowing remote users to explore the immersive visual environment independently of the local user's head direction. We describe the system design of JackIn Head and report the evaluation results of real-time image stabilization and alleviation of cybersickness. Then, through an exploratory observation study, we investigate how individuals can remotely interact, communicate with, and assist each other with our system. We report our observation and analysis of inter-personal communication, demonstrating the effectiveness of our system in augmenting remote collaboration.

  13. Loss-of-function mutation in Hippo suppressed enlargement of lysosomes and neurodegeneration caused by dFIG4 knockdown.

    PubMed

    Kushimura, Yukie; Azuma, Yumiko; Mizuta, Ikuko; Muraoka, Yuuka; Kyotani, Akane; Yoshida, Hideki; Tokuda, Takahiko; Mizuno, Toshiki; Yamaguchi, Masamitsu

    2018-05-08

    Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy, and more than 80 CMT-causing genes have been identified to date. CMT4J is caused by a loss-of-function mutation in the Factor-Induced-Gene 4 (FIG4) gene, the product of which plays important roles in endosome-lysosome homeostasis. We hypothesized that Mammalian sterile 20-like kinase (MST) 1 and 2, tumor-suppressor genes, are candidate modifiers of CMT4J. We therefore examined the interaction between dFIG4 and Hippo (hpo), Drosophila counterparts of FIG4 and MSTs, respectively, using the Drosophila CMT4J model with the knockdown of dFIG4. The loss-of-function allele of hpo improved the rough eye morphology, locomotive dysfunction accompanied by structural defects in the presynaptic terminals of motoneurons, and the enlargement of lysosomes caused by the knockdown of dFIG4. Therefore, we identified hpo as a modifier of phenotypes induced by the knockdown of dFIG4. These results in Drosophila may provide an insight into the pathogenesis of CMT4J and contribute toward the development of disease-modifying therapy for CMT. We also identified the regulation of endosome-lysosome homeostasis as a novel probable function of Hippo/MST.

  14. "Delays and Vexation": Jack London and the Russo-Japanese War.

    ERIC Educational Resources Information Center

    Sweeney, Michael S.

    1998-01-01

    Contributes to scholarship on journalism history and censorship by discussing Jack London's efforts as a war correspondent to cover the Russo-Japanese War in Korea and Manchuria in 1904. Focuses on the difficulties he encountered as a result of systematic and highly restrictive censorship by the Japanese. (SR)

  15. The influence of musical cadence into aquatic jumping jacks kinematics.

    PubMed

    Costa, Mário J; Oliveira, Cristiana; Teixeira, Genoveva; Marinho, Daniel A; Silva, António J; Barbosa, Tiago M

    2011-01-01

    The aim of this study was to analyze the relationships between the head-out aquatic exercise "Jumping jacks" kinematics and the musical cadence in healthy and fit subjects. Five young women, with at least one year of experience conducting head- out aquatic programs were videotaped in the frontal plane, with a pair of cameras providing a double projection (above and below the water surface). Subjects performed an incremental protocol of five bouts (120 b·min(-1), 135 b·min(-1), 150 b·min(-1), 165 b·min(-1) and 180 b·min(-1)) with 16 full cycles of the "Jumping jacks" exercise. Data processing and calculation of upper limbs' (i.e. hands), lower limbs' (i.e. feet) and center of mass' 2D linear velocity and displacement were computed with the software Ariel Performance Analysis System and applying the 2D-DLT algorithm. Subjects decreased the cycle period during the incremental protocol. Significant and negative relationships with the musical cadence were verified for the center of mass and upper limbs vertical displacement. On the other hand, for the lower limbs lateral velocity, a significant and positive relationship was observed. It is concluded that expert and fit subjects increase the lower limb's velocity to maintain the range of motion, while the upper limb's displacement is reduced to coupe the music cadence. Key pointsWhile performing the Jumping Jacks, expert and fit subjects increase their lower limbs segmental velocity to maintain the range of motion.The upper limbs displacement is reduced to maintain the music cadence.Expert and fit subjects present similar response for alternating or simultaneously head-out aquatic exercises when increasing the music cadence.

  16. Forest floor fuels in red and jack pine stands

    Treesearch

    James K. Brown

    1966-01-01

    An investigation to determine the quantity and density of forest floor fuels in red pine (Pinus resinosa Ait.) and jack pine (Pinus banksiana Lamb.) stands was conducted on National Forests in Michigan and Minnesota. The study was designed to answer three questions: How much fuel per acre exits in individual layers of the forest floor? How reliably can weight of...

  17. Jack Nicholson: A Reel and Real-Life Contribution to Neurosciences.

    PubMed

    Tripathi, Manjul; Purkayastha, Moushumi; Rai, Ashutosh; Mukherjee, Kanchan K

    2017-05-01

    Though primarily considered entertainment, cinema is a mirror of society. The portrayal of neurosciences is common in cinema, but none could do it better than Jack Nicholson. We give a brief overview of his contribution to neurosciences by analyzing his acting skills. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. AmeriFlux CA-Ojp Saskatchewan - Western Boreal, Mature Jack Pine

    DOE Data Explorer

    Black, Andrew T. [University of British Columbia

    2017-01-01

    This is the AmeriFlux version of the carbon flux data for the site CA-Ojp Saskatchewan - Western Boreal, Mature Jack Pine. Site Description - 53.91634° N, 104.69203° W, elavation of 579.27 m, BOREAS 1994, BERMS climate measurements began Mar. 1997 and flux measurements Aug. 1999

  19. Cluster analysis on a sphere: Application to magnetizations from metasediments of the Jack Hills, Western Australia

    NASA Astrophysics Data System (ADS)

    Bono, Richard K.; Tarduno, John A.; Dare, Matthew S.; Mitra, Gautam; Cottrell, Rory D.

    2018-02-01

    Metasediments of the Jack Hills contain the oldest known terrestrial minerals in the form of zircons nearly 4.4 billion years old. Paleointensity data from these zircons provide evidence for a Hadean geodynamo as old as 4.2 billion years old. Given the importance of these zircons for constraining the earliest history of the core, it is vital to understand the fidelity of the zircon record. A fundamental aspect providing context for the preservation of primary magnetic signals is the nature of overprints predicted to have been imparted on rocks of the Jack Hills due to Archean to Proterozoic metamorphic events. To be viable magnetic records of a Hadean geodynamo, zircon magnetization directions should differ from these secondary magnetizations. To evaluate these secondary magnetizations, we report paleomagnetic analyses of a comprehensive sampling of 68 quartzite cobble-sized clasts from the Jack Hills metasediments ∼0.5 to 1.0 km from the Discovery Site (which has yielded the oldest zircons and paleofield estimates). While application of standard paleomagnetic tests suggests that the ensemble of cobble directions cannot be distinguished from those drawn from a random distribution, a new cluster analysis of directions on a sphere and non-parametric resampling approaches reveal significant directions amongst subsets of the data. One, isolated at the lowest temperature analyzed [200 to 300 °C, Declination (Dec.) = 316.8°, Inclination (Inc.) = - 51.1 °] appears to be dominated by the present day field. Another, isolated at higher (but still relatively low unblocking temperatures that we call "intermediate", of ∼350-500 °C, Dec. = 243.8°, Inc. = 9.5°) agrees with a magnetic overprint isolated from the secondary Cr-Fe mica fuchsite isolated from the Jack Hills Discovery site, passing a field test at the 80% confidence level. No evidence is found in our data, or in the data of others collected on similar Jack Hills lithologies, for a widespread 1 Ga

  20. Comparison of lodgepole and jack pine resin chemistry: implications for range expansion by the mountain pine beetle, Dendroctonus ponderosae (Coleoptera: Curculionidae).

    PubMed

    Clark, Erin L; Pitt, Caitlin; Carroll, Allan L; Lindgren, B Staffan; Huber, Dezene P W

    2014-01-01

    The mountain pine beetle, Dendroctonus ponderosae, is a significant pest of lodgepole pine in British Columbia (BC), where it has recently reached an unprecedented outbreak level. Although it is native to western North America, the beetle can now be viewed as a native invasive because for the first time in recorded history it has begun to reproduce in native jack pine stands within the North American boreal forest. The ability of jack pine trees to defend themselves against mass attack and their suitability for brood success will play a major role in the success of this insect in a putatively new geographic range and host. Lodgepole and jack pine were sampled along a transect extending from the beetle's historic range (central BC) to the newly invaded area east of the Rocky Mountains in north-central Alberta (AB) in Canada for constitutive phloem resin terpene levels. In addition, two populations of lodgepole pine (BC) and one population of jack pine (AB) were sampled for levels of induced phloem terpenes. Phloem resin terpenes were identified and quantified using gas chromatography. Significant differences were found in constitutive levels of terpenes between the two species of pine. Constitutive α-pinene levels - a precursor in the biosynthesis of components of the aggregation and antiaggregation pheromones of mountain pine beetle - were significantly higher in jack pine. However, lower constitutive levels of compounds known to be toxic to bark beetles, e.g., 3-carene, in jack pine suggests that this species could be poorly defended. Differences in wounding-induced responses for phloem accumulation of five major terpenes were found between the two populations of lodgepole pine and between lodgepole and jack pine. The mountain pine beetle will face a different constitutive and induced phloem resin terpene environment when locating and colonizing jack pine in its new geographic range, and this may play a significant role in the ability of the insect to persist in

  1. Heritability and intertrait correlations in breeding subpopulations of jack pine

    Treesearch

    Don E. Riemenschneider

    1985-01-01

    Twenty breeding populations of jack pine were established in 1979 and 1980 in Minnesota, Wisconsin, and Michigan. Four populations were index populations and were each established at 4 locations by research cooperators. Sixteen populations were applied breeding populations and were established at single locations by public and private cooperators. Combined analysis of...

  2. Astronaut Jack Fischer at Air and Space Museum

    NASA Image and Video Library

    2017-11-03

    NASA astronaut Jack Fischer sticks his finger in a liquid that was just boiling by vacuum, during a Stem in 30 experiment, Friday, Nov. 3, 2017 at Smithsonian's National Air and Space Museum in Washington. During Expedition 52, Fischer completed hundreds of scientific experiments and two spacewalks, and concluded his 136-day mission onboard the International Space Station, when he landed in a remote area near the town of Zhezkazgan, Kazakhstan in September 2017. Photo Credit: (NASA/Aubrey Gemignani)

  3. Astronaut Jack Fischer at Air and Space Museum

    NASA Image and Video Library

    2017-11-03

    An audience member asks a question after a presentation by NASA astronaut Jack Fischer about his time onboard the International Space Station (ISS) during Expeditions 51/52, Friday, Nov. 3, 2017 at Smithsonian's National Air and Space Museum in Washington. During Expedition 52, Fischer completed hundreds of scientific experiments and two spacewalks, and concluded his 136-day mission when he landed in a remote area near the town of Zhezkazgan, Kazakhstan in September 2017. Photo Credit: (NASA/Aubrey Gemignani)

  4. Variations in foliar monoterpenes across the range of jack pine reveal three widespread chemotypes: implications to host expansion of invasive mountain pine beetle.

    PubMed

    Taft, Spencer; Najar, Ahmed; Godbout, Julie; Bousquet, Jean; Erbilgin, Nadir

    2015-01-01

    The secondary compounds of pines (Pinus) can strongly affect the physiology, ecology and behaviors of the bark beetles (Coleoptera: Curculionidae, Scolytinae) that feed on sub-cortical tissues of hosts. Jack pine (Pinus banksiana) has a wide natural distribution range in North America (Canada and USA) and thus variations in its secondary compounds, particularly monoterpenes, could affect the host expansion of invasive mountain pine beetle (Dendroctonus ponderosae), which has recently expanded its range into the novel jack pine boreal forest. We investigated monoterpene composition of 601 jack pine trees from natural and provenance forest stands representing 63 populations from Alberta to the Atlantic coast. Throughout its range, jack pine exhibited three chemotypes characterized by high proportions of α-pinene, β-pinene, or limonene. The frequency with which the α-pinene and β-pinene chemotypes occurred at individual sites was correlated to climatic variables, such as continentality and mean annual precipitation, as were the individual α-pinene and β-pinene concentrations. However, other monoterpenes were generally not correlated to climatic variables or geographic distribution. Finally, while the enantiomeric ratios of β-pinene and limonene remained constant across jack pine's distribution, (-):(+)-α-pinene exhibited two separate trends, thereby delineating two α-pinene phenotypes, both of which occurred across jack pine's range. These significant variations in jack pine monoterpene composition may have cascading effects on the continued eastward spread and success of D. ponderosae in the Canadian boreal forest.

  5. Practical breeding programs for jack pine in the Lake States

    Treesearch

    James P. King

    1973-01-01

    Jack pine (Pinus banksiana Lamb.) is the most common pine in the Lake States and is expected to play an increasingly important role in Lake States planting programs. This species is easy to plant successfully even on dry, sandy soils. Its rapid growth during the first 30 years makes it suitable for intensive-culture, short-rotation forestry. And it...

  6. Healing of the Acutely Injured Anterior Cruciate Ligament: Functional Treatment with the ACL-Jack, a Dynamic Posterior Drawer Brace

    PubMed Central

    Reischl, Nikolaus; Rönn, Karolin; Magnusson, Robert A.; Gautier, Emanuel; Jakob, Roland P.

    2016-01-01

    Background. The injured anterior cruciate ligament (ACL) has a limited healing capacity leading to persisting instability. Hypothesis/Purpose. To study if the application of a brace, producing a dynamic posterior drawer force, after acute ACL injury reduces initial instability. Study Design. Cohort study. Methods. Patients treated with the ACL-Jack brace were compared to controls treated with primary ACL reconstruction und controls treated nonsurgically with functional rehabilitation. Measurements included anterior laxity (Rolimeter), clinical scores (Lysholm, Tegner, and IKDC), and MRI evaluation. Patients were followed up to 24 months. Results. Patients treated with the ACL-Jack brace showed a significant improvement of anterior knee laxity comparable to patients treated with ACL reconstruction, whereas laxity persisted after nonsurgical functional rehabilitation. The failure risk (secondary reconstruction necessary) of the ACL-Jack group was however 21% (18 of 86) within 24 months. Clinical scores were similar in all treatment groups. Conclusion. Treatment of acute ACL tears with the ACL-Jack brace leads to improved anterior knee laxity compared to nonsurgical treatment with functional rehabilitation. PMID:28053787

  7. Heavy duty precision leveling jacks expedite setup time on horizontal boring mill

    NASA Technical Reports Server (NTRS)

    Dellenbaugh, W.; Jones, C.

    1966-01-01

    Leveling jack is a precise alignment tool which expedites the setup of components or assemblies up to 2500 pounds on horizontal boring mills. This tool eliminates the necessity of wedges and blocks to shim the components to proper position.

  8. Tall oil precursors and turpentine in Jack and Eastern White Pine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Conner, A.H.; Diehl, M.A.; Rowe, J.W.

    1980-04-01

    The tall oil precursors and turpentine from jack pine (Pinus banksiana Lamb.) and eastern white pine (Pinus strobus L.) were investigated. The tall oil precursors (resin acids, fatty acids, and unsaponifiables were determined by chemical fractionation of the nonvolatile diethyl ether extractives (NVEE) of these speices: (approximate % resin acids, % fatty acids, % unsaponifiables, and % acids other that fatty and resin acids) - jack pine sapwood (10, 60, 10, 20%), heartwood (38, 12, 6, 44%); eastern white pine sapwood (11, 57, 9, 22%), and heartwood (11, 18, 10, 62%). The resin acids were a mixture of the pimaricmore » and abietic acids common to pines. In addition, eastern white pine contained major amounts of the resin acid, anticopalic acid. The fatty acids were predominately oleic, linoleic, and 5, 9, 12-octadecatrienoic acids. The unsaponsiables were a complex mixture of diterpenes and sterols (mainly campesterol and sitosterol). On treating these species with paraquat, lightwood occurred in the sapwood but not in the heartwood areas as we have oberved with other pines. The NVEE of the lightwood areas contained increased amounts of resin acids, unsaponifiables, and acids other than fatty and resin acids. The total fatty acid content was essentially unchanged. Since fatty acid components are preferentially lost by esterification with neutral alcoholic constituents in the unsaponifiables during the distillation refining of crude tall oil, the increased unsaponifiables relative to the constant fatty acid content might result in a net reduction in fatty acid recovery from lightered trees. The turpentine content of both jack and eastern white pine increased on lightering and was primarily a mixture of ..cap alpha..- and ..beta..-pinene.« less

  9. Jack Mezirow's Conceptualisation of Adult Transformative Learning: A Review

    ERIC Educational Resources Information Center

    Calleja, Colin

    2014-01-01

    This paper traces the evolution of Jack Mezirow's transformative learning theory and its conceptualisation. It discusses the three major influences, namely Thomas Khun's philosophical conception of paradigm, Freire's conception of conscientisation and consciousness growth, and Habermas' domains of learning and the discussion of…

  10. Hippo in Super Resolution from Super Panorama

    NASA Image and Video Library

    1998-07-03

    This view of the "Hippo," 25 meters to the west of the lander, was produced by combining the "Super Panorama" frames from the IMP camera. Super resolution was applied to help to address questions about the texture of this rock and what it might tell us about its mode of origin. The composite color frames that make up this anaglyph were produced for both the right and left eye of the IMP. These composites consist of more than 15 frames per eye (because multiple sequences covered the same area), taken with different color filters that were enlarged by 500% and then co-added using Adobe Photoshop to produce, in effect, a super-resolution panchromatic frame that is sharper than an individual frame would be. These panchromatic frames were then colorized with the red, green, and blue filtered images from the same sequence. The color balance was adjusted to approximate the true color of Mars. The anaglyph view was produced by combining the left with the right eye color composite frames by assigning the left eye composite view to the red color plane and the right eye composite view to the green and blue color planes (cyan), to produce a stereo anaglyph mosaic. This mosaic can be viewed in 3-D on your computer monitor or in color print form by wearing red-blue 3-D glasses. http://photojournal.jpl.nasa.gov/catalog/PIA01421

  11. Lithium in Jack Hills zircons: Evidence for extensive weathering of Earth's earliest crust

    NASA Astrophysics Data System (ADS)

    Ushikubo, Takayuki; Kita, Noriko T.; Cavosie, Aaron J.; Wilde, Simon A.; Rudnick, Roberta L.; Valley, John W.

    2008-08-01

    In situ Li analyses of 4348 to 3362 Ma detrital zircons from the Jack Hills, Western Australia by SIMS reveal that the Li abundances (typically 10 to 60 ppm) are commonly over 10,000 times higher than in zircons crystallized from mantle-derived magmas and in mantle-derived zircon megacrysts (typically < 2 ppb). High Li concentrations in zircons (10 to 250 ppm) have also been found in igneous zircons from three continental parent rocks: granites, Li-rich pegmatites, and migmatites in pelitic metasediment. The substitution of trivalent cations (REEs and Y) in zircon correlates with Li + 1 and P + 5 , suggesting that an interstitial site for Li, as well as the xenotime substitution for P, provides charge balance for REEs. Li is thus fixed in the zircon structure by coupled substitutions, and diffusive changes in [Li] composition are rate-limited by slow diffusion of REEs. The Jack Hills zircons also have fractionated lithium isotope ratios ( δ7Li = - 19 to + 13‰) about five times more variable than those recorded in primitive ocean floor basalts (2 to 8‰), but similar to continental crust and its weathering products. Values of δ7Li below - 10‰ are found in zircons that formed as early as 4300 Ma. The high Li compositions indicate that primitive magmas were not the source of Jack Hills zircons and the fractionated values of δ7Li suggest that highly weathered regolith was sampled by these early Archean magmas. These new Li data provide evidence that the parent magmas of ancient zircons from Jack Hills incorporated materials from the surface of the Earth that interacted at low temperature with liquid water. These data support the hypothesis that continental-type crust and oceans existed by 4300 Ma, within 250 million years of the formation of Earth and the low values of δ7Li suggest that weathering was extensive in the early Archean.

  12. Jack D. Fellows: Congressional Science Fellow

    NASA Astrophysics Data System (ADS)

    Jack D. Fellows has been selected as the 1983-84 AGU Congressional Science Fellow. Last week he began his 1-year stint on Capitol Hill as AGU's seventh Congressional Science Fellow.Fellows received his Ph.D. earlier this year from the civil engineering department at the University of Maryland, College Park. For his dissertation he developed a management system using regional geographic information for hydrologic models. His work applied remote sensing data to the decision-making processes of regional planning organizations concerned with hydrology and natural resource management. The Maryland National Capital Park and Planning Commission has integrated Fellows' work into their programs on water resource and environmental planning; his approach also is being used for forest and water resource planning near Freiburg, Baden-Wurtemberg, West Germany.

  13. Analytical results and sample locality maps of stream-sediment, heavy-mineral-concentrate, and rock samples from the Little Jacks Creek (ID-111-006), Big Jacks Creek (ID-111-007C), Duncan Creek (ID-111-0007B), and Upper Deep Creek (ID-111-044) Wilderness Study Areas, Owyhee County, Idaho

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Erickson, M.S.; Gent, C.A.; Bradley, L.A.

    1989-01-01

    A U.S. Geological Survey report detailing the analytical results and sample locality maps of stream-sediment, heavy-mineral-concentrate, and rock samples from the Little Jacks Creek, Big Jacks Creek, Duncan Creek, and Upper Deep Creek Wilderness Study Areas, Owyhee County, Idaho

  14. Skylab (SL)-3 - Astronaut Jack R. Lousma - Utensils

    NASA Image and Video Library

    1973-09-19

    S73-34198 (1 Aug. 1973) --- A close-up view of the hands of astronaut Jack R. Lousma, Skylab 3 pilot, using a silverware utensil to gather food at the food station, in this photographic reproduction taken from a television transmission made by a color TV camera aboard the Skylab space station in Earth orbit. Astronaut Alan L. Bean, commander, had just zoomed the TV camera in for this close-up of the food tray following a series of wide shots of Lousma at the food station. Photo credit: NASA

  15. Forest Modeling of Jack Pine Trees for BOREAS

    NASA Technical Reports Server (NTRS)

    Moghhadam, Mahta; Saatchi, Sasan

    1994-01-01

    As a part of the intensive field campaign for the Boreal forest ecosystem-atmosphere research (BOREAS) project in August 1993, the NASA/JPL AIRSAR covered an area of about 100 km by 100 km near the Prince Albert National Park in Saskatchewan, Canada. At the same time, ground-truth measurements were made in several stands which have been selected as the primary study sites, as well as in some auxiliary sites. This paper focuses on an area including Jack Pine stands in the Nipawin area near the park.

  16. ROCK and RHO Playlist for Preimplantation Development: Streaming to HIPPO Pathway and Apicobasal Polarity in the First Cell Differentiation.

    PubMed

    Alarcon, Vernadeth B; Marikawa, Yusuke

    2018-01-01

    In placental mammalian development, the first cell differentiation produces two distinct lineages that emerge according to their position within the embryo: the trophectoderm (TE, placenta precursor) differentiates in the surface, while the inner cell mass (ICM, fetal body precursor) forms inside. Here, we discuss how such position-dependent lineage specifications are regulated by the RHOA subfamily of small GTPases and RHO-associated coiled-coil kinases (ROCK). Recent studies in mouse show that activities of RHO/ROCK are required to promote TE differentiation and to concomitantly suppress ICM formation. RHO/ROCK operate through the HIPPO signaling pathway, whose cell position-specific modulation is central to establishing unique gene expression profiles that confer cell fate. In particular, activities of RHO/ROCK are essential in outside cells to promote nuclear localization of transcriptional co-activators YAP/TAZ, the downstream effectors of HIPPO signaling. Nuclear localization of YAP/TAZ depends on the formation of apicobasal polarity in outside cells, which requires activities of RHO/ROCK. We propose models of how RHO/ROCK regulate lineage specification and lay out challenges for future investigations to deepen our understanding of the roles of RHO/ROCK in preimplantation development. Finally, as RHO/ROCK may be inhibited by certain pharmacological agents, we discuss their potential impact on human preimplantation development in relation to fertility preservation in women.

  17. ADVANCED DESIGNS OF MAGNETIC JACK-TYPE CONTROL ROD DRIVE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, J.N.

    1959-11-01

    The magnetic jack is a device for positioning the control rods In a nuclear reactor, especially in a reactor containing water under pressure. Magnetic actuation precludes the need for shaft seals and eliminates the problems associated with mechanisms operating in water. It consists of a pressure shell, four sets of external stationary magnet coils (hold, grip, lift, pull down), and one Internal moving part (ammature) that impants linear motion to a cluster of rods. (W.L.H.)

  18. Astronaut Jack Lousma - Inflight Medical Support System (IMSS) - JSC

    NASA Image and Video Library

    1973-01-01

    S73-28423 (16 June 1973) --- Astronaut Jack R. Lousma, Skylab 3 pilot, reaches into a medical kit, part of the Inflight Medical Support System (IMSS), during training for the second manned Skylab Earth-orbital mission. This activity took place in the OWS trainer in the Mission Simulation and Training Facility at the Johnson Space Center (JSC). Other Skylab 3 crewmen are astronaut Alan L. Bean, commander, and scientist-astronaut Owen K. Garriott, science pilot. Photo credit: NASA

  19. Cross-Reactivity of Polyclonal Antibodies against Canavalia ensiformis (Jack Bean) Urease and Helicobacter pylori Urease Subunit A Fragments.

    PubMed

    Kaminski, Zbigniew Jerzy; Relich, Inga; Konieczna, Iwona; Kaca, Wieslaw; Kolesinska, Beata

    2018-01-01

    Overlapping decapeptide fragments of H. pylori urease subunit A (UreA) were synthesized and tested with polyclonal antibodies against Canavalia ensiformis (Jack bean) urease. The linear epitopes of UreA identified using the dot blot method were then examined using epitope mapping. For this purpose, series of overlapping fragments of UreA, frameshifted ± four amino acid residues were synthesized. Most of the UreA epitopes which reacted with the Jack bean urease polyclonal antibodies had been recognized in previous studies by monoclonal antibodies against H. pylori urease. Fragments 11 - 24, 21 - 33, and 31 - 42 were able to interact with the Jack bean urease antibodies, giving stable immunological complexes. However, the lack of recognition by these antibodies of all the components in the peptide map strongly suggests that a non-continuous (nonlinear) epitope is located on the N-terminal domain of UreA. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  20. Height and seasonal growth pattern of jack pine full-sib families

    Treesearch

    Don E. Riemenschneider

    1981-01-01

    Total tree height, seasonal shoot elongation, dates of growth initiation and cessation, and mean daily growth rate were measured and analyzed for a population of jack pine full-sib families derived from inter-provenance crosses. Parental provenance had no effect on these variables although this may have been due to small sample size. Progenies differed significantly...

  1. From Word to World: Reflections on the Ezra Jack Keats Award.

    ERIC Educational Resources Information Center

    Herrera, Juan Felipe

    2000-01-01

    Discusses the author's Ezra Jack Keats Award for "Calling the Doves/El Canto de las Palomas" (1995), a bilingual picture book based on his childhood in the farm working camps of Central California. Concludes that writers must stay true to the deep sources of multicultural experience, for positive change, and for the magical pictures and poems. (SG)

  2. Microphysics-based black carbon aging in a global CTM: constraints from HIPPO observations and implications for global black carbon budget

    NASA Astrophysics Data System (ADS)

    He, Cenlin; Li, Qinbin; Liou, Kuo-Nan; Qi, Ling; Tao, Shu; Schwarz, Joshua P.

    2016-03-01

    We develop and examine a microphysics-based black carbon (BC) aerosol aging scheme that accounts for condensation, coagulation, and heterogeneous chemical oxidation processes in a global 3-D chemical transport model (GEOS-Chem) by interpreting the BC measurements from the HIAPER Pole-to-Pole Observations (HIPPO, 2009-2011) using the model. We convert aerosol mass in the model to number concentration by assuming lognormal aerosol size distributions and compute the microphysical BC aging rate (excluding chemical oxidation aging) explicitly from the condensation of soluble materials onto hydrophobic BC and the coagulation between hydrophobic BC and preexisting soluble particles. The chemical oxidation aging is tested in the sensitivity simulation. The microphysical aging rate is ˜ 4 times higher in the lower troposphere over source regions than that from a fixed aging scheme with an e-folding time of 1.2 days. The higher aging rate reflects the large emissions of sulfate-nitrate and secondary organic aerosol precursors hence faster BC aging through condensation and coagulation. In contrast, the microphysical aging is more than 5-fold slower than the fixed aging in remote regions, where condensation and coagulation are weak. Globally, BC microphysical aging is dominated by condensation, while coagulation contribution is largest over eastern China, India, and central Africa. The fixed aging scheme results in an overestimate of HIPPO BC throughout the troposphere by a factor of 6 on average. The microphysical scheme reduces this discrepancy by a factor of ˜ 3, particularly in the middle and upper troposphere. It also leads to a 3-fold reduction in model bias in the latitudinal BC column burden averaged along the HIPPO flight tracks, with largest improvements in the tropics. The resulting global annual mean BC lifetime is 4.2 days and BC burden is 0.25 mg m-2, with 7.3 % of the burden at high altitudes (above 5 km). Wet scavenging accounts for 80.3 % of global BC

  3. Microphysics-based black carbon aging in a global CTM: constraints from HIPPO observations and implications for global black carbon budget

    NASA Astrophysics Data System (ADS)

    He, C.; Li, Q.; Liou, K. N.; Qi, L.; Tao, S.; Schwarz, J. P.

    2015-11-01

    We develop and examine a microphysics-based black carbon (BC) aerosol aging scheme that accounts for condensation and coagulation processes in a global 3-D chemical transport model (GEOS-Chem) by interpreting the BC measurements from the HIAPER Pole-to-Pole Observations (HIPPO, 2009-2011) using the model. We convert aerosol mass in the model to number concentration by assuming lognormal aerosol size distributions and compute the microphysical BC aging rate explicitly from the condensation of soluble materials onto hydrophobic BC and the coagulation between hydrophobic BC and preexisting soluble particles. The resulting aging rate is ∼ 4 times higher in the lower troposphere over source regions than that from a fixed aging scheme with an e-folding time of 1.2 days. The higher aging rate reflects the large emissions of sulfate-nitrate and secondary organic aerosol precursors hence faster BC aging through condensation and coagulation. In contrast, the microphysical aging is more than fivefold slower than the fixed aging in remote regions, where condensation and coagulation are weak. Globally BC microphysical aging is dominated by condensation, while coagulation contribution is largest over East China, India, and Central Africa. The fixed aging scheme results in an overestimate of HIPPO BC throughout the troposphere by a factor of 6 on average. The microphysical scheme reduces this discrepancy by a factor of ∼ 3, particularly in the middle and upper troposphere. It also leads to a threefold reduction in model bias in the latitudinal BC column burden averaged along the HIPPO flight tracks, with largest improvements in the tropics. The resulting global annual mean BC lifetime is 4.2 days and BC burden is 0.25 mg m-2, with 7.3 % of the burden at high altitudes (above 5 km). Wet scavenging accounts for 80.3 % of global BC deposition. We find that in source regions the microphysical aging rate is insensitive to aerosol size distribution, condensation threshold, and

  4. Climate-diameter growth relationships of black spruce and jack pine trees in boreal Ontario, Canada.

    PubMed

    Subedi, Nirmal; Sharma, Mahadev

    2013-02-01

    To predict the long-term effects of climate change - global warming and changes in precipitation - on the diameter (radial) growth of jack pine (Pinus banksiana Lamb.) and black spruce (Picea mariana [Mill.] B.S.P.) trees in boreal Ontario, we modified an existing diameter growth model to include climate variables. Diameter chronologies of 927 jack pine and 1173 black spruce trees, growing in the area from 47°N to 50°N and 80°W to 92°W, were used to develop diameter growth models in a nonlinear mixed-effects approach. Our results showed that the variables long-term average of mean growing season temperature, precipitation during wettest quarter, and total precipitation during growing season were significant (alpha = 0.05) in explaining variation in diameter growth of the sample trees. Model results indicated that higher temperatures during the growing season would increase the diameter growth of jack pine trees, but decrease that of black spruce trees. More precipitation during the wettest quarter would favor the diameter growth of both species. On the other hand, a wetter growing season, which may decrease radiation inputs, increase nutrient leaching, and reduce the decomposition rate, would reduce the diameter growth of both species. Moreover, our results indicated that future (2041-2070) diameter growth rate may differ from current (1971-2000) growth rates for both species, with conditions being more favorable for jack pine than black spruce trees. Expected future changes in the growth rate of boreal trees need to be considered in forest management decisions. We recommend that knowledge of climate-growth relationships, as represented by models, be combined with learning from adaptive management to reduce the risks and uncertainties associated with forest management decisions. © 2012 Blackwell Publishing Ltd.

  5. ASTRONAUT LOUSMA, JACK - EGRESS - SKYLAB 3 COMMAND MODULE - PACIFIC

    NASA Image and Video Library

    1973-09-25

    S73-36435 (25 Sept. 1973) --- Astronaut Jack R. Lousma, Skylab 3 pilot, egresses the Skylab 3 Command Module aboard the prime recovery ship, USS New Orleans, during recovery operations in the Pacific Ocean. Astronauts Lousma; Alan L. Bean, commander; and Owen L. Garriott, science pilot, had just completed a successful 59-day visit to the Skylab space station in Earth orbit. The Skylab 3 spacecraft splashed down in the Pacific about 230 miles southwest of San Diego, California. Photo credit: NASA

  6. Using Transom Jack in the Human Engineering Analysis of the Materials Science Research Rack-1 and Quench Module Insert

    NASA Technical Reports Server (NTRS)

    Dunn, Mariea C.; Alves, Jeffrey R.; Hutchinson, Sonya L.

    1999-01-01

    This paper describes the human engineering analysis performed on the Materials Science Research Rack-1 and Quench Module Insert (MSRR-1/QMI) using Transom Jack (Jack) software. The Jack software was used to model a virtual environment consisting of the MSRR-1/QMI hardware configuration and human figures representing the 95th percentile male and 5th percentile female. The purpose of the simulation was to assess the human interfaces in the design for their ability to meet the requirements of the Pressurized Payloads Interface Requirements Document - International Space Program, Revision C (SSP 57000). Jack was used in the evaluation because of its ability to correctly model anthropometric body measurements and the physical behavior of astronauts working in microgravity, which is referred to as the neutral body posture. The Jack model allows evaluation of crewmember interaction with hardware through task simulation including but not limited to collision avoidance behaviors, hand/eye coordination, reach path planning, and automatic grasping to part contours. Specifically, this virtual simulation depicts the human figures performing the QMI installation and check-out, sample cartridge insertion and removal, and gas bottle drawer removal. These tasks were evaluated in terms of adequate clearance in reach envelopes, adequate accessibility in work envelopes, appropriate line of sight in visual envelopes, and accommodation of full size range for male and female stature maneuverability. The results of the human engineering analysis virtual simulation indicate that most of the associated requirements of SSP 57000 were met. However, some hardware design considerations and crew procedures modifications are recommended to improve accessibility, provide an adequate work envelope, reduce awkward body posture, and eliminate permanent protrusions.

  7. Activation of the yeast Hippo pathway by phosphorylation-dependent assembly of signaling complexes.

    PubMed

    Rock, Jeremy M; Lim, Daniel; Stach, Lasse; Ogrodowicz, Roksana W; Keck, Jamie M; Jones, Michele H; Wong, Catherine C L; Yates, John R; Winey, Mark; Smerdon, Stephen J; Yaffe, Michael B; Amon, Angelika

    2013-05-17

    Scaffold-assisted signaling cascades guide cellular decision-making. In budding yeast, one such signal transduction pathway called the mitotic exit network (MEN) governs the transition from mitosis to the G1 phase of the cell cycle. The MEN is conserved and in metazoans is known as the Hippo tumor-suppressor pathway. We found that signaling through the MEN kinase cascade was mediated by an unusual two-step process. The MEN kinase Cdc15 first phosphorylated the scaffold Nud1. This created a phospho-docking site on Nud1, to which the effector kinase complex Dbf2-Mob1 bound through a phosphoserine-threonine binding domain, in order to be activated by Cdc15. This mechanism of pathway activation has implications for signal transmission through other kinase cascades and might represent a general principle in scaffold-assisted signaling.

  8. Impacts of fiber orientation and milling on observed crystallinity in jack pine

    Treesearch

    Umesh P. Agarwal; Sally A. Ralph; Richard S. Reiner; Roderquita K. Moore; Carlos Baez

    2014-01-01

    Influences of fiber orientation and milling on wood cellulose crystallinity were studied using jack pine wood. The fiber orientation effects were measured by sampling rectangular wood blocks in radial, tangential, and cross-sectional orientations. The influence of milling was studied by analyzing the unsieved and sieved milled wood fractions (all

  9. Single step purification of concanavalin A (Con A) and bio-sugar production from jack bean using glucosylated magnetic nano matrix.

    PubMed

    Kim, Ho Myeong; Cho, Eun Jin; Bae, Hyeun-Jong

    2016-08-01

    Jack bean (JB, Canavalia ensiformis) is the source of bio-based products, such as proteins and bio-sugars that contribute to modern molecular biology and biomedical research. In this study, the use of jack bean was evaluated as a source for concanavalin A (Con A) and bio-sugar production. A novel method for purifying Con A from JBs was successfully developed using a glucosylated magnetic nano matrix (GMNM) as a physical support, which facilitated easy separation and purification of Con A. In addition, the enzymatic conversion rate of 2% (w/v) Con A extracted residue to bio-sugar was 98.4%. Therefore, this new approach for the production of Con A and bio-sugar is potentially useful for obtaining bio-based products from jack bean. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Astronaut Jack Lousma participates in EVA to deploy twin pole solar shield

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Astronaut Jack R. Lousma, Skylab 3 pilot, participates in the August 6, 1973 extravehicular activity (EVA) during which he and Astronauts Owen K. Garriott, science pilot, deployed the twin pole solar shield to help shade the Orbital Workshop (OWS). Note the reflection of the Apollo Telescope Mount and the Earth in Lousma's helmet visor.

  11. Mosaic Stunting in jack pine seedlings in a northern Michigan bareroot nursery

    Treesearch

    Lynette Potvin; R. Kasten Dumroese; Martin F. Jurgensen; Dana Richter

    2010-01-01

    Mosaic, or patchy, stunting of bareroot conifer seedlings is thought to be caused by deficiencies of mycorrhizal fungi following fumigation, resulting in reduced nutrient uptake, particularly phosphorus. Mosaic stunting of jack pine (Pinus banksiana) seedlings was observed in 2005 at the USDA Forest Service JW Toumey Nursery in Watersmeet, MI. We initiated a study to...

  12. Rereading "The Jack-Roller:" Hidden Histories in Sociology and Social Work

    ERIC Educational Resources Information Center

    Shaw, Ian

    2009-01-01

    I revisit one of the iconic Chicago School studies, Clifford Shaw's "The Jack-Roller". A naive reading of Shaw's book leaves the reader with a sense of having been inducted into a melange of what we now know as "sociology" and "social work," but which to Shaw seems a coherent stance. I suggest that this is close to the heart of how things were,…

  13. Jack-of-all-trades effects drive biodiversity–ecosystem multifunctionality relationships in European forests

    PubMed Central

    van der Plas, Fons; Manning, Peter; Allan, Eric; Scherer-Lorenzen, Michael; Verheyen, Kris; Wirth, Christian; Zavala, Miguel A.; Hector, Andy; Ampoorter, Evy; Baeten, Lander; Barbaro, Luc; Bauhus, Jürgen; Benavides, Raquel; Benneter, Adam; Berthold, Felix; Bonal, Damien; Bouriaud, Olivier; Bruelheide, Helge; Bussotti, Filippo; Carnol, Monique; Castagneyrol, Bastien; Charbonnier, Yohan; Coomes, David; Coppi, Andrea; Bastias, Cristina C.; Muhie Dawud, Seid; De Wandeler, Hans; Domisch, Timo; Finér, Leena; Gessler, Arthur; Granier, André; Grossiord, Charlotte; Guyot, Virginie; Hättenschwiler, Stephan; Jactel, Hervé; Jaroszewicz, Bogdan; Joly, François-Xavier; Jucker, Tommaso; Koricheva, Julia; Milligan, Harriet; Müller, Sandra; Muys, Bart; Nguyen, Diem; Pollastrini, Martina; Raulund-Rasmussen, Karsten; Selvi, Federico; Stenlid, Jan; Valladares, Fernando; Vesterdal, Lars; Zielínski, Dawid; Fischer, Markus

    2016-01-01

    There is considerable evidence that biodiversity promotes multiple ecosystem functions (multifunctionality), thus ensuring the delivery of ecosystem services important for human well-being. However, the mechanisms underlying this relationship are poorly understood, especially in natural ecosystems. We develop a novel approach to partition biodiversity effects on multifunctionality into three mechanisms and apply this to European forest data. We show that throughout Europe, tree diversity is positively related with multifunctionality when moderate levels of functioning are required, but negatively when very high function levels are desired. For two well-known mechanisms, ‘complementarity' and ‘selection', we detect only minor effects on multifunctionality. Instead a third, so far overlooked mechanism, the ‘jack-of-all-trades' effect, caused by the averaging of individual species effects on function, drives observed patterns. Simulations demonstrate that jack-of-all-trades effects occur whenever species effects on different functions are not perfectly correlated, meaning they may contribute to diversity–multifunctionality relationships in many of the world's ecosystems. PMID:27010076

  14. Southwestern Surgical Congress Jack A. Barney award competition presenters - Where are they now?

    PubMed

    Kothari, Shanu N; Kallies, Kara J

    2017-12-01

    Resident research presentations at surgical conferences may encourage future research endeavors. 2010-2016 SWSC annual meeting programs were reviewed for presenters eligible for the Jack Barney award. Award recipients from 1987 to 2016 were included. There were 100 unique presenters eligible for the Jack Barney award, and 28 unique award recipients. Thirty-six (82%) presenters currently practice in a community setting, 5 (11%) at a university hospital, 2 (5%) internationally, and 1 (2%) in a military hospital. Scholarly articles were published by 41% of presenters. Sixteen of the 28 recipients (57%) practice in community hospitals, and 9 (32%) practice in university settings; 3 are still in training. Twenty recipients (71%) published after residency. Thirty percent and 25% of presenters and recipients are SWSC members, respectively. Peer-reviewed publications were frequent among eligible presenters and award recipients. Encouraging presenters to become SWSC members provides an opportunity for improved retention. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Jack-of-all-trades effects drive biodiversity-ecosystem multifunctionality relationships in European forests.

    PubMed

    van der Plas, Fons; Manning, Peter; Allan, Eric; Scherer-Lorenzen, Michael; Verheyen, Kris; Wirth, Christian; Zavala, Miguel A; Hector, Andy; Ampoorter, Evy; Baeten, Lander; Barbaro, Luc; Bauhus, Jürgen; Benavides, Raquel; Benneter, Adam; Berthold, Felix; Bonal, Damien; Bouriaud, Olivier; Bruelheide, Helge; Bussotti, Filippo; Carnol, Monique; Castagneyrol, Bastien; Charbonnier, Yohan; Coomes, David; Coppi, Andrea; Bastias, Cristina C; Muhie Dawud, Seid; De Wandeler, Hans; Domisch, Timo; Finér, Leena; Gessler, Arthur; Granier, André; Grossiord, Charlotte; Guyot, Virginie; Hättenschwiler, Stephan; Jactel, Hervé; Jaroszewicz, Bogdan; Joly, François-Xavier; Jucker, Tommaso; Koricheva, Julia; Milligan, Harriet; Müller, Sandra; Muys, Bart; Nguyen, Diem; Pollastrini, Martina; Raulund-Rasmussen, Karsten; Selvi, Federico; Stenlid, Jan; Valladares, Fernando; Vesterdal, Lars; Zielínski, Dawid; Fischer, Markus

    2016-03-24

    There is considerable evidence that biodiversity promotes multiple ecosystem functions (multifunctionality), thus ensuring the delivery of ecosystem services important for human well-being. However, the mechanisms underlying this relationship are poorly understood, especially in natural ecosystems. We develop a novel approach to partition biodiversity effects on multifunctionality into three mechanisms and apply this to European forest data. We show that throughout Europe, tree diversity is positively related with multifunctionality when moderate levels of functioning are required, but negatively when very high function levels are desired. For two well-known mechanisms, 'complementarity' and 'selection', we detect only minor effects on multifunctionality. Instead a third, so far overlooked mechanism, the 'jack-of-all-trades' effect, caused by the averaging of individual species effects on function, drives observed patterns. Simulations demonstrate that jack-of-all-trades effects occur whenever species effects on different functions are not perfectly correlated, meaning they may contribute to diversity-multifunctionality relationships in many of the world's ecosystems.

  16. Transcriptome resources and functional characterization of monoterpene synthases for two host species of the mountain pine beetle, lodgepole pine (Pinus contorta) and jack pine (Pinus banksiana)

    PubMed Central

    2013-01-01

    Background The mountain pine beetle (MPB, Dendroctonus ponderosae) epidemic has affected lodgepole pine (Pinus contorta) across an area of more than 18 million hectares of pine forests in western Canada, and is a threat to the boreal jack pine (Pinus banksiana) forest. Defence of pines against MPB and associated fungal pathogens, as well as other pests, involves oleoresin monoterpenes, which are biosynthesized by families of terpene synthases (TPSs). Volatile monoterpenes also serve as host recognition cues for MPB and as precursors for MPB pheromones. The genes responsible for terpene biosynthesis in jack pine and lodgepole pine were previously unknown. Results We report the generation and quality assessment of assembled transcriptome resources for lodgepole pine and jack pine using Sanger, Roche 454, and Illumina sequencing technologies. Assemblies revealed transcripts for approximately 20,000 - 30,000 genes from each species and assembly analyses led to the identification of candidate full-length prenyl transferase, TPS, and P450 genes of oleoresin biosynthesis. We cloned and functionally characterized, via expression of recombinant proteins in E. coli, nine different jack pine and eight different lodgepole pine mono-TPSs. The newly identified lodgepole pine and jack pine mono-TPSs include (+)-α-pinene synthases, (-)-α-pinene synthases, (-)-β-pinene synthases, (+)-3-carene synthases, and (-)-β-phellandrene synthases from each of the two species. Conclusion In the absence of genome sequences, transcriptome assemblies are important for defence gene discovery in lodgepole pine and jack pine, as demonstrated here for the terpenoid pathway genes. The product profiles of the functionally annotated mono-TPSs described here can account for the major monoterpene metabolites identified in lodgepole pine and jack pine. PMID:23679205

  17. Assessment of possible sources of microbiological contamination in the water column and streambed sediment of the Jacks Fork, Ozark National Scenic Riverways, Missouri - Phase III

    USGS Publications Warehouse

    Davis, Jerri V.; Barr, Miya N.

    2006-01-01

    In 1998, a 5 river-mile reach of the Jacks Fork was included on Missouri's list of impaired waters as required by Section 303(d) of the Federal Clean Water Act. The identified pollutant on the Jacks Fork was fecal coliform bacteria. The length of the impaired reach was changed to 7 miles on the Missouri 2002 303(d) list because of data indicating the fecal coliform bacteria problem existed over a broader area. The U.S. Geological Survey, in cooperation with the National Park Service, conducted a study to better understand the extent and sources of microbiological contamination within the Jacks Fork from Alley Spring to the mouth, which includes the 7-mile 303(d) reach. Ten sites were sampled from June 2003 through October 2003 and from June 2004 through October 2004. Water-column and streambed sediment samples were collected from main-stem and tributary sites mostly during base-flow conditions during a variety of recreational season river uses and analyzed for fecal coliform and Escherichia coli bacteria. Isolates of Escherichia coli obtained from water samples collected at five sites were submitted for rep-PCR analysis to identify presumptive sources of fecal indicator bacteria in the Jacks Fork. Results indicate that recreational users (including boaters and swimmers) are not the primary source of fecal coliform bacteria in the Jacks Fork; rather, the presence of fecal coliform bacteria is associated with other animals, of which horses are the primary source. Increases in fecal coliform bacteria densities in the Jacks Fork are associated with cross-country horseback trail-riding events.

  18. Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals

    PubMed Central

    Losick, Vicki P.; Jun, Albert S.; Spradling, Allan C.

    2016-01-01

    Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues. PMID:26958853

  19. Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals.

    PubMed

    Losick, Vicki P; Jun, Albert S; Spradling, Allan C

    2016-01-01

    Tissue integrity and homeostasis often rely on the proliferation of stem cells or differentiated cells to replace lost, aged, or damaged cells. Recently, we described an alternative source of cell replacement- the expansion of resident, non-dividing diploid cells by wound-induced polyploidization (WIP). Here we show that the magnitude of WIP is proportional to the extent of cell loss using a new semi-automated assay with single cell resolution. Hippo and JNK signaling regulate WIP; unexpectedly however, JNK signaling through AP-1 limits rather than stimulates the level of Yki activation and polyploidization in the Drosophila epidermis. We found that polyploidization also quantitatively compensates for cell loss in a mammalian tissue, mouse corneal endothelium, where increased cell death occurs with age in a mouse model of Fuchs Endothelial Corneal Dystrophy (FECD). Our results suggest that WIP is an evolutionarily conserved homeostatic mechanism that maintains the size and synthetic capacity of adult tissues.

  20. Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells

    NASA Astrophysics Data System (ADS)

    Sun, Yubing; Yong, Koh Meng Aw; Villa-Diaz, Luis G.; Zhang, Xiaoli; Chen, Weiqiang; Philson, Renee; Weng, Shinuo; Xu, Haoxing; Krebsbach, Paul H.; Fu, Jianping

    2014-06-01

    Our understanding of the intrinsic mechanosensitive properties of human pluripotent stem cells (hPSCs), in particular the effects that the physical microenvironment has on their differentiation, remains elusive. Here, we show that neural induction and caudalization of hPSCs can be accelerated by using a synthetic microengineered substrate system consisting of poly(dimethylsiloxane) micropost arrays (PMAs) with tunable mechanical rigidities. The purity and yield of functional motor neurons derived from hPSCs within 23 days of culture using soft PMAs were improved more than fourfold and tenfold, respectively, compared with coverslips or rigid PMAs. Mechanistic studies revealed a multi-targeted mechanotransductive process involving Smad phosphorylation and nucleocytoplasmic shuttling, regulated by rigidity-dependent Hippo/YAP activities and actomyosin cytoskeleton integrity and contractility. Our findings suggest that substrate rigidity is an important biophysical cue influencing neural induction and subtype specification, and that microengineered substrates can thus serve as a promising platform for large-scale culture of hPSCs.

  1. A-jacks and Aquawrap installations in Utah : scour revetment performance evaluation, final report, December 2009.

    DOT National Transportation Integrated Search

    2009-12-01

    This is a performance evaluation report for A-Jacks, an articulated concrete block designed to protect bridge elements exposed to the river scouring forces, and for Aquawrap, a glass fiber reinforced polymer designed to protect and strengthen bridge ...

  2. Exploratory investigation of the HIPPO gas-jet target fluid dynamic properties

    NASA Astrophysics Data System (ADS)

    Meisel, Zach; Shi, Ke; Jemcov, Aleksandar; Couder, Manoel

    2016-08-01

    In order to optimize the performance of gas-jet targets for future nuclear reaction measurements, a detailed understanding of the dependence of the gas-jet properties on experiment design parameters is required. Common methods of gas-jet characterization rely on measuring the effective thickness using nuclear elastic scattering and energy loss techniques; however, these tests are time intensive and limit the range of design modifications which can be explored to improve the properties of the jet as a nuclear reaction target. Thus, a more rapid jet-characterization method is desired. We performed the first steps towards characterizing the gas-jet density distribution of the HIPPO gas-jet target at the University of Notre Dame's Nuclear Science Laboratory by reproducing results from 20Ne(α,α)20Ne elastic scattering measurements with computational fluid dynamics (CFD) simulations performed with the state-of-the-art CFD software ANSYS Fluent. We find a strong sensitivity to experimental design parameters of the gas-jet target, such as the jet nozzle geometry and ambient pressure of the target chamber. We argue that improved predictive power will require moving to three-dimensional simulations and additional benchmarking with experimental data.

  3. Growth of hybrid poplars, white spruce, and jack pine under various artificial lights.

    Treesearch

    Pamela S. Roberts; J. Zavitkovski

    1981-01-01

    Describes the energy consumption and biological effects of fluorescent, incandescent, and high pressure sodium lighting on the growth of poplars, white spruce, and jack pine in a greenhouse. At similar light levels the biological effects of all three light sources were similar. The incandescent lamps consumed several times more energy than the other two light...

  4. AmeriFlux CA-SJ2 Saskatchewan - Western Boreal, Jack Pine forest harvested in 2002

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barr, Alan; Black, Andrew T.

    This is the AmeriFlux version of the carbon flux data for the site CA-SJ2 Saskatchewan - Western Boreal, Jack Pine forest harvested in 2002. Site Description - 53.944737° N, 104.649340° W, BERMS flux and climate measurements to begin by Mar 2003

  5. Manuka honey (Leptospermum scoparium) inhibits jack bean urease activity due to methylglyoxal and dihydroxyacetone.

    PubMed

    Rückriemen, Jana; Klemm, Oliver; Henle, Thomas

    2017-09-01

    Manuka honey (Leptospermum scoparium) exerts a strong antibacterial effect. Bacterial enzymes are an important target for antibacterial compounds. The enzyme urease produces ammonia and enables bacteria to adapt to an acidic environment. A new enzymatic assay, based on photometric detection of ammonia with ninhydrin, was developed to study urease activity. Methylglyoxal (MGO) and its precursor dihydroxyacetone (DHA), which are naturally present in manuka honey, were identified as jack bean urease inhibitors with IC 50 values of 2.8 and 5.0mM, respectively. Urease inhibition of manuka honey correlates with its MGO and DHA content. Non-manuka honeys, which lack MGO and DHA, showed significantly less urease inhibition. MGO depletion from manuka honey with glyoxalase reduced urease inhibition. Therefore, urease inhibition by manuka honey is mainly due to MGO and DHA. The results obtained with jack bean urease as a model urease, may contribute to the understanding of bacterial inhibition by manuka honey. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Direct Comparisons of Ice Cloud Macro- and Microphysical Properties Simulated by the Community Atmosphere Model CAM5 with HIPPO Aircraft Observations

    NASA Astrophysics Data System (ADS)

    Wu, C.; Liu, X.; Diao, M.; Zhang, K.; Gettelman, A.

    2015-12-01

    A dominant source of uncertainty within climate system modeling lies in the representation of cloud processes. This is not only because of the great complexity in cloud microphysics, but also because of the large variations of cloud amount and macroscopic properties in time and space. In this study, the cloud properties simulated by the Community Atmosphere Model version 5.4 (CAM5.4) are evaluated using the HIAPER Pole-to-Pole Observations (HIPPO, 2009-2011). CAM5.4 is driven by the meteorology (U, V, and T) from GEOS5 analysis, while water vapor, hydrometeors and aerosols are calculated by the model itself. For direct comparison of CAM5.4 and HIPPO observations, model output is collocated with HIPPO flights. Generally, the model has an ability to capture specific cloud systems of meso- to large-scales. In total, the model can reproduce 80% of observed cloud occurrences inside model grid boxes, and even higher (93%) for ice clouds (T≤-40°C). However, the model produces plenty of clouds that are not presented in the observation. The model also simulates significantly larger cloud fraction including for ice clouds compared to the observation. Further analysis shows that the overestimation is a result of bias in relative humidity (RH) in the model. The bias of RH can be mostly attributed to the discrepancies of water vapor, and to a lesser extent to those of temperature. Down to the micro-scale level of ice clouds, the model can simulate reasonably well the magnitude of ice and snow number concentration (Ni, with diameter larger than 75 μm). However, the model simulates fewer occurrences of Ni>50 L-1. This can be partially ascribed to the low bias of aerosol number concentration (Naer, with diameter between 0.1-1 μm) simulated by the model. Moreover, the model significantly underestimates both the number mean diameter (Di,n) and the volume mean diameter (Di,v) of ice/snow. The result shows that the underestimation may be related to a weaker positive relationship

  7. AmeriFlux CA-SJ1 Saskatchewan - Western Boreal, Jack Pine forest harvested in 1994

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barr, Alan

    This is the AmeriFlux version of the carbon flux data for the site CA-SJ1 Saskatchewan - Western Boreal, Jack Pine forest harvested in 1994. Site Description - 53.908408° N, 104.655885° W, elavation of 580m, BERMS climate and flux measurements began in Spring 2001

  8. Astronaut Jack Lousma seen outside Skylab space station during EVA

    NASA Image and Video Library

    1973-08-06

    S73-31976 (5 Aug. 1973) --- Astronaut Jack R. Lousma, Skylab 3 pilot, is seen outside the Skylab space station in Earth orbit during the Aug. 5, 1973 Skylab 3 extravehicular activity (EVA) in this photographic reproduction taken from a television transmission made by a color TV camera aboard the space station. Scientist-astronaut Owen K. Garriott, Skylab 3 science pilot, participated in the EVA with Lousma. During the EVA the two crewmen deployed the twin pole solar shield to help shade the Orbital Workshop. Photo credit: NASA

  9. P2Y2 Nucleotide Receptor Prompts Human Cardiac Progenitor Cell Activation by Modulating Hippo Signaling.

    PubMed

    Khalafalla, Farid G; Greene, Steven; Khan, Hashim; Ilves, Kelli; Monsanto, Megan M; Alvarez, Roberto; Chavarria, Monica; Nguyen, Jonathan; Norman, Benjamin; Dembitsky, Walter P; Sussman, Mark A

    2017-11-10

    Autologous stem cell therapy using human c-Kit + cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged patients with HF with genetic predispositions and comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impair overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with proregenerative molecules ex vivo is crucial for improving the therapeutic outcome in patients with HF. To improve hCPC proliferation and migration responses that are critical for regeneration by targeting proregenerative P2Y 2 nucleotide receptor (P2Y 2 R) activated by extracellular ATP and UTP molecules released following injury/stress. c-Kit + hCPCs were isolated from cardiac tissue of patients with HF undergoing left ventricular assist device implantation surgery. Correlations between P2 nucleotide receptor expression and hCPC growth kinetics revealed downregulation of select P2 receptors, including P2Y 2 R, in slow-growing hCPCs compared with fast growers. hCPC proliferation and migration significantly improved by overexpressing or stimulating P2Y 2 R. Mechanistically, P2Y 2 R-induced proliferation and migration were dependent on activation of YAP (yes-associated protein)-the downstream effector of Hippo signaling pathway. Proliferation and migration of functionally impaired hCPCs are enhanced by P2Y 2 R-mediated YAP activation, revealing a novel link between extracellular nucleotides released during injury/stress and Hippo signaling-a central regulator of cardiac regeneration. Functional correlations exist between hCPC phenotypic properties and P2 purinergic receptor expression. Lack of P2Y 2 R and other crucial purinergic stress detectors could compromise hCPC responsiveness to presence of extracellular stress signals. These findings set the stage for subsequent studies to assess purinergic signaling modulation as a

  10. Astronaut Jack Lousma in Lower Body Negative Pressure Device

    NASA Image and Video Library

    1973-08-09

    S73-34180 (7 Aug. 1973) --- A medium close-up view of astronaut Jack R. Lousma, Skylab 3 pilot, in the Lower Body Negative Pressure Device (LBNPD), as astronaut Alan L. Bean, commander, works around the leg band area. This portion of the LBNPD MO-92 experiment was televised on Aug. 7, 1973. The LBNPD experiment is to provide information concerning the time course of cardiovascular adaptation during flight, and to provide in-flight data for predicting the degree of orthostatic intolerence and impairment of physical capacity to be expected upon returning to Earth environment. The bicycle ergometer is in the background, partially visible behind Bean. Photo credit: NASA

  11. Orthopaedic jack for scoliosis surgery purposes: Concept and design

    NASA Astrophysics Data System (ADS)

    Supriadi, Sugeng; Radhana, Rakha M.; Hidayanto, Taufik Eko; Whulanza, Yudan; Ali, Notario, Nanda; Rahyussalim

    2017-02-01

    Scoliosis surgery is one of the most difficult orthopedic surgery that have been committed today as the failure rate of orthopedic surgery for adult patients is 15%. Aside from the long duration of surgery, this surgical failure is caused by failure in biomedical instrumentation. Furthermore, this kind of failure is causing inefficiency of the surgery. With current known orthopedic surgery method, three surgeons are needed in a single orthopedic surgery. In fact, a single surgery can take up to 8 hours to be done, which increases the risk of surgical failure. Based on this problem, authors hope that our orthopedic jacks could solve the problem.

  12. Influence of seedbed, light environment, and elevated night temperature on growth and carbon allocation in pitch pine (Pinus rigida) and jack pine (Pinus banksiana) seedlings

    Treesearch

    Michael E. Day; Jessica L. Schedlbauer; William H. Livingston; Michael S. Greenwood; Alan S. White; John C. Brissette

    2005-01-01

    Jack pine (Pinus banksiana Lamb.) and pitch pine (Pinus rigida Mill.) are two autecologically similar species that occupy generally disjunct ranges in eastern North America. Jack pine is boreal in distribution, while pitch pine occurs at temperate latitudes. The two species co-occur in a small number of stands along a 'tension...

  13. A sperm-agglutinating lectin from seeds of Jack fruit (Artocarpus heterophyllus).

    PubMed

    Namjuntra, P; Muanwongyathi, P; Chulavatnatol, M

    1985-04-30

    A lectin specific for N-acetylgalactosamine was isolated from seed extract of Jack fruit (Artocarpus heterophyllus) by ammonium sulfate precipitation, followed by affinity chromatography on a Affigel-galactosamine-agarose column. The lectin possessed agglutinating activities for human and rat sperm as well as human red blood cells. It was found to have Mr = 62,000 consisting of two dissimilar subunits of Mr = 18,000 and 13,000. It also cross-reacted with an antibody against the lectin of Osage Orange (Maclura pomifera).

  14. Jack'd, a Mobile Social Networking Application: A Site of Exclusion Within a Site of Inclusion.

    PubMed

    Bartone, Michael D

    2018-01-01

    User-generated smartphone applications have created a new level of virtual connectivity for gay males, one in which users can create profiles and meet other users as nearby or as far away as possible. For those within close proximity, the other users can be considered their "virtual neighbors." Although the applications are theoretically designed to be places of inclusion and not exclusion, where any gay male with economic means can download an application, many profiles have been created that exclude other users. Through an examination of profiles on one such application, Jack'd, exclusion is found in the way users celebrate and reinforce ideas of traditional masculinity and denigrate and reinforce stereotypic ideas of femininity embodied by some gay men. Jack'd, and other user-generated smartphone applications, can be read as virtual neighborhoods where one is excluded based on their gender performance.

  15. Physical and Chemical Characterization Of Greater Yam (Dioscorea Alata) And Jack Bean (Canavalia Ensiformis) - Based Composite Flour

    NASA Astrophysics Data System (ADS)

    Affandi, D. R.; Praseptiangga, D.; Nirmala, F. S.; Sigit Amanto, B.; Atmaka, W.

    2017-04-01

    Indonesia is a tropical country that has great potential in agriculture. Tubers and legumes as examples of the potential commodities are needed to be more developed. Flour production is one of the best alternatives to be chosen as the downstream stage of the tubers and legumes utilization. Greater yam (Dioscorea alata) and jack bean (Canavalia ensiformis) were used in this study. This study was conducted to determine best formula of composite flour based on physical, chemical, and functional characterization of composite flour produced. Variations of formula used was the ratio of greater yam flour and jack bean flour, which were 85:15 (F1), 70:30 (F2), 55:45 (F3), respectively, and this study was conducted using completely randomized design (CRD). The formula variations didn’t show any significant effect on the water absorption capability, water holding capacity (WHC), oil holding capacity (OHC), swelling power, and starch content of the composite flour. However, the formula variations had a significant influence on the colour, proximate parameters, amylose and amylopectin content, resistant starch content, dietary fibre, total phenol, and antioxidant activity of the composite flour produced. Considering the results of physical, chemical, and functional characteristics of composite flour, formula (F1) was selected as the best composite flour developed from greater yam and jack bean flours.

  16. The lodgepole × jack pine hybrid zone in Alberta, Canada: a stepping stone for the mountain pine beetle on its journey East across the boreal forest?

    PubMed

    Lusebrink, Inka; Erbilgin, Nadir; Evenden, Maya L

    2013-09-01

    Historical data show that outbreaks of the tree killing mountain pine beetle are often preceded by periods of drought. Global climate change impacts drought frequency and severity and is implicated in the range expansion of the mountain pine beetle into formerly unsuitable habitats. Its expanded range has recently reached the lodgepole × jack pine hybrid zone in central Alberta, Canada, which could act as a transition from its historical lodgepole pine host to a jack pine host present in the boreal forest. This field study tested the effects of water limitation on chemical defenses of mature trees against mountain pine beetle-associated microorganisms and on beetle brood success in lodgepole × jack pine hybrid trees. Tree chemical defenses as measured by monoterpene emission from tree boles and monoterpene concentration in needles were greater in trees that experienced water deficit compared to well-watered trees. Myrcene was identified as specific defensive compound, since it significantly increased upon inoculation with dead mountain pine beetles. Beetles reared in bolts from trees that experienced water deficit emerged with a higher fat content, demonstrating for the first time experimentally that drought conditions benefit mountain pine beetles. Further, our study demonstrated that volatile chemical emission from tree boles and phloem chemistry place the hybrid tree chemotype in-between lodgepole pine and jack pine, which might facilitate the host shift from lodgepole pine to jack pine.

  17. Astronaut Jack Lousma participates in EVA to deploy twin pole solar shield

    NASA Image and Video Library

    1973-08-06

    SL3-115-1833 (6 Aug. 1973) --- Astronaut Jack R. Lousma, Skylab 3 pilot, participates in the Aug. 6, 1973, extravehicular activity (EVA) during which he and astronaut Owen K. Garriott, science pilot, deployed the twin pole solar shield to help shade the Orbital Workshop (OWS). Note the striking reflection of the Earth in Lousma?s helmet visor. This photograph was taken with a 70mm hand-held Hasselblad camera. Photo credit: NASA

  18. Astronaut Jack Lousma looks at map of Earth in ward room of Skylab cluster

    NASA Image and Video Library

    1973-08-01

    S73-34193 (1 Aug. 1973) --- Astronaut Jack R. Lousma, Skylab 3 pilot, looks at a map of Earth at the food table in the ward room of the Orbital Workshop (OWS). In this photographic reproduction taken from a television transmission made by a color TV camera aboard the Skylab space station cluster in Earth orbit. Photo credit: NASA

  19. Reconstruction of the genome-scale co-expression network for the Hippo signaling pathway in colorectal cancer.

    PubMed

    Dehghanian, Fariba; Hojati, Zohreh; Hosseinkhan, Nazanin; Mousavian, Zaynab; Masoudi-Nejad, Ali

    2018-05-26

    The Hippo signaling pathway (HSP) has been identified as an essential and complex signaling pathway for tumor suppression that coordinates proliferation, differentiation, cell death, cell growth and stemness. In the present study, we conducted a genome-scale co-expression analysis to reconstruct the HSP in colorectal cancer (CRC). Five key modules were detected through network clustering, and a detailed discussion of two modules containing respectively 18 and 13 over and down-regulated members of HSP was provided. Our results suggest new potential regulatory factors in the HSP. The detected modules also suggest novel genes contributing to CRC. Moreover, differential expression analysis confirmed the differential expression pattern of HSP members and new suggested regulatory factors between tumor and normal samples. These findings can further reveal the importance of HSP in CRC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Comparisons of cirrus cloud properties between polluted and pristine air based on in-situ observations from the NSF HIPPO, EU INCA and NASA ATTREX campaigns

    NASA Astrophysics Data System (ADS)

    Diao, M.; Schumann, U.; Jensen, J. B.; Minikin, A.

    2015-12-01

    The radiative forcing of cirrus clouds is influenced by microphysical (e.g., ice crystal number concentration and size distribution) and macroscopic properties. Currently it is still unclear how the formation of cirrus clouds and their microphysical properties are influenced by anthropogenic emissions. In this work, we use airborne in-situ observations to compare cirrus cloud properties between polluted and pristine regions. Our dataset includes: the NSF HIAPER Pole-to-Pole Observations (HIPPO) Global campaign (2009-2011), the EU Interhemispheric Differences In Cirrus Properties from Anthropogenic Emissions (INCA) campaign (2000) and the NASA Airborne Tropical Tropopause Experiment (ATTREX) campaign (2014). The combined dataset include observations of both extratropical (HIPPO and INCA) and tropical (ATTREX) cirrus, over the Northern and Southern Hemispheres. We use the in-situ measured carbon monoxide (CO) mixing ratio as a pollution indicator, and compare ice microphysical properties (i.e., ice crystal number concentration (Nc) and number-weighted mean diameter (Dc)) between air masses with higher and lower CO. All analyses are restricted to T ≤ -40°C. By analyzing ice crystals (Fast-2DC, 87.5-1600 µm) in HIPPO, we found that Dc decreases with increasing CO concentration at multiple constant pressure levels. In addition, analysis of INCA data shows that Nc and extinction of small ice particles (FSSP 3-20 µm) increases with increasing CO. Particles < 87.5 µm in Fast-2DC data are not considered due to uncertainty in sample volume, and the FSSP measurements are subject to possible shattering. We further analyze the ice crystals (SPEC FCDP, 1-50 µm) in the tropical tropopause layer in ATTREX. At -70°C to -90°C, we found that the average Nc (Dc) increases (decreases) at higher CO. Overall, our results suggest that extratropical and tropical cirrus are likely to have more numerous small ice particles, when sampled in the more polluted background. Back

  1. Fatty Acid Composition of Novel Host Jack Pine Do Not Prevent Host Acceptance and Colonization by the Invasive Mountain Pine Beetle and Its Symbiotic Fungus

    PubMed Central

    Ishangulyyeva, Guncha; Najar, Ahmed; Curtis, Jonathan M.

    2016-01-01

    Fatty acids are major components of plant lipids and can affect growth and development of insect herbivores. Despite a large literature examining the roles of fatty acids in conifers, relatively few studies have tested the effects of fatty acids on insect herbivores and their microbial symbionts. Particularly, whether fatty acids can affect the suitability of conifers for insect herbivores has never been studied before. Thus, we evaluated if composition of fatty acids impede or facilitate colonization of jack pine (Pinus banksiana) by the invasive mountain pine beetle (Dendroctonus ponderosae) and its symbiotic fungus (Grosmannia clavigera). This is the first study to examine the effects of tree fatty acids on any bark beetle species and its symbiotic fungus. In a novel bioassay, we found that plant tissues (hosts and non-host) amended with synthetic fatty acids at concentrations representative of jack pine were compatible with beetle larvae. Likewise, G. clavigera grew in media amended with lipid fractions or synthetic fatty acids at concentrations present in jack pine. In contrast, fatty acids and lipid composition of a non-host were not suitable for the beetle larvae or the fungus. Apparently, concentrations of individual, rather than total, fatty acids determined the suitability of jack pine. Furthermore, sampling of host and non-host tree species across Canada demonstrated that the composition of jack pine fatty acids was similar to the different populations of beetle’s historical hosts. These results demonstrate that fatty acids composition compatible with insect herbivores and their microbial symbionts can be important factor defining host suitability to invasive insects. PMID:27583820

  2. Development of a well-behaved site index equation: jack pine in north central Ontario

    Treesearch

    J. C. G. Goelz; T. E. Burke

    1992-01-01

    A base-age invariant site index equation for jack pine based on the Chapman-Richards function was produced that satisfied nine criteria of preferred behavior for site index equations. A difference form of the Chapman-Richards equation produced the best behavior; height equaled site index at base age, and the shape of the curves reflected the data. The data structure...

  3. Astronaut Jack Lousma hooks up cable for rate gyro six pack during EVA

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Astronaut Jack R. Lousma, Skylab 3 pilot, hooks up a 23 ft. 2 in. connecting cable for the rate gyro six pack during extravehicular activity (EVA) on August 24, 1973, as senn in this photographic reproduction taken from a color television tranmsission made by a TV camera aboard the Skylab space station in Earth orbit. The rate gyros were mounted inside the Multiple Docking Adapter opposite the Apollo Telescope Mount control and display console.

  4. Direct comparisons of ice cloud macro- and microphysical properties simulated by the Community Atmosphere Model version 5 with HIPPO aircraft observations

    NASA Astrophysics Data System (ADS)

    Wu, Chenglai; Liu, Xiaohong; Diao, Minghui; Zhang, Kai; Gettelman, Andrew; Lu, Zheng; Penner, Joyce E.; Lin, Zhaohui

    2017-04-01

    In this study we evaluate cloud properties simulated by the Community Atmosphere Model version 5 (CAM5) using in situ measurements from the HIAPER Pole-to-Pole Observations (HIPPO) campaign for the period of 2009 to 2011. The modeled wind and temperature are nudged towards reanalysis. Model results collocated with HIPPO flight tracks are directly compared with the observations, and model sensitivities to the representations of ice nucleation and growth are also examined. Generally, CAM5 is able to capture specific cloud systems in terms of vertical configuration and horizontal extension. In total, the model reproduces 79.8 % of observed cloud occurrences inside model grid boxes and even higher (94.3 %) for ice clouds (T ≤ -40 °C). The missing cloud occurrences in the model are primarily ascribed to the fact that the model cannot account for the high spatial variability of observed relative humidity (RH). Furthermore, model RH biases are mostly attributed to the discrepancies in water vapor, rather than temperature. At the micro-scale of ice clouds, the model captures the observed increase of ice crystal mean sizes with temperature, albeit with smaller sizes than the observations. The model underestimates the observed ice number concentration (Ni) and ice water content (IWC) for ice crystals larger than 75 µm in diameter. Modeled IWC and Ni are more sensitive to the threshold diameter for autoconversion of cloud ice to snow (Dcs), while simulated ice crystal mean size is more sensitive to ice nucleation parameterizations than to Dcs. Our results highlight the need for further improvements to the sub-grid RH variability and ice nucleation and growth in the model.

  5. Jack-knife stretching promotes flexibility of tight hamstrings after 4 weeks: a pilot study.

    PubMed

    Sairyo, Koichi; Kawamura, Takeshi; Mase, Yasuyoshi; Hada, Yasushi; Sakai, Toshinori; Hasebe, Kiyotaka; Dezawa, Akira

    2013-08-01

    Tight hamstrings are reported to be one of the causes of low back pain. However, there have been few reports on effective stretching procedures for the tight hamstrings. The so-called jack-knife stretch, an active-static type of stretching, can efficiently increase the flexibility of tight hamstrings. To evaluate hamstring tightness before and after the 4-week stretching protocol in healthy volunteer adults and patients aged under 18 years with low back pain. For understanding the hamstrings tightness, we measured two parameters including (1) finger to floor distance (FFD) and (2) pelvis forward inclination angle (PFIA). Eight healthy adult volunteers who had no lumbar or hip problems participated in this study (mean age: 26.8 years). All lacked flexibility and their FFD were positive before the experiment. Subjects performed 2 sets of the jack-knife stretch every day for 4 weeks. One set consisted of 5 repetitions, each held for 5 s. Before and during the 4-week experiment, the FFD and PFIA of toe-touching tests were measured weekly. For 17 of the sports players aged under 18, only FFD was measured. In adult volunteers, FFD was 14.1 ± 6.1 cm before the experiment and decreased to -8.1 ± 3.7 cm by the end of week 4, indicating a gain in flexibility of 22.2 cm. PFIA was 50.6 ± 8.2 before the experiment and 83.8 ± 5.8 degrees after. Before and after the experiment, the differences were significant (p < 0.05). For those aged under 18, FFD was 8.1 ± 8.0 and -9.6 ± 6.8, before and after the stretching, respectively. This difference was significant (p < 0.05). The jack-knife stretch is a useful active-static stretching technique to efficiently increase flexibility of tight hamstrings.

  6. Pervasive remagnetization of detrital zircon host rocks in the Jack Hills, Western Australia and implications for records of the early geodynamo

    NASA Astrophysics Data System (ADS)

    Weiss, Benjamin P.; Maloof, Adam C.; Tailby, Nicholas; Ramezani, Jahandar; Fu, Roger R.; Hanus, Veronica; Trail, Dustin; Bruce Watson, E.; Harrison, T. Mark; Bowring, Samuel A.; Kirschvink, Joseph L.; Swanson-Hysell, Nicholas L.; Coe, Robert S.

    2015-11-01

    It currently is unknown when Earth's dynamo magnetic field originated. Paleomagnetic studies indicate that a field with an intensity similar to that of the present day existed 3.5 billion years ago (Ga). Detrital zircon crystals found in the Jack Hills of Western Australia are some of the very few samples known to substantially predate this time. With crystallization ages ranging from 3.0-4.38 Ga, these zircons might preserve a record of the missing first billion years of Earth's magnetic field history. However, a key unknown is the age and origin of magnetization in the Jack Hills zircons. The identification of >3.9 Ga (i.e., Hadean) field records requires first establishing that the zircons have avoided remagnetization since being deposited in quartz-rich conglomerates at 2.65-3.05 Ga. To address this issue, we have conducted paleomagnetic conglomerate, baked contact, and fold tests in combination with U-Pb geochronology to establish the timing of the metamorphic and alteration events and the peak temperatures experienced by the zircon host rocks. These tests include the first conglomerate test directly on the Hadean-zircon bearing conglomerate at Erawandoo Hill. Although we observed little evidence for remagnetization by recent lightning strikes, we found that the Hadean zircon-bearing rocks and surrounding region have been pervasively remagnetized, with the final major overprinting likely due to thermal and/or aqueous effects from the emplacement of the Warakurna large igneous province at ∼1070 million years ago (Ma). Although localized regions of the Jack Hills might have escaped complete remagnetization, there currently is no robust evidence for pre-depositional (>3.0 Ga) magnetization in the Jack Hills detrital zircons.

  7. View of Jack Lousma's hands using silverware to gather food at food station

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A close-up view of Skylab 3 pilot Jack Lousma's hands using a silverware utensil to gather food at the food station, in this photographic reproduction taken from a television transmission made by a color TV camera aboard the Skylab space station in Earth orbit. Astronaut Alan L. Bean, commander, had just zoomed the TV camera in for this closeup of the food tray following a series of wide shots of Lousma at the food station.

  8. Transcriptome Meta-Analysis of Lung Cancer Reveals Recurrent Aberrations in NRG1 and Hippo Pathway Genes

    PubMed Central

    Dhanasekaran, Saravana M.; Balbin, O. Alejandro; Chen, Guoan; Nadal, Ernest; Kalyana-Sundaram, Shanker; Pan, Jincheng; Veeneman, Brendan; Cao, Xuhong; Malik, Rohit; Vats, Pankaj; Wang, Rui; Huang, Stephanie; Zhong, Jinjie; Jing, Xiaojun; Iyer, Matthew; Wu, Yi-Mi; Harms, Paul W.; Lin, Jules; Reddy, Rishindra; Brennan, Christine; Palanisamy, Nallasivam; Chang, Andrew C.; Truini, Anna; Truini, Mauro; Robinson, Dan R.; Beer, David G.; Chinnaiyan, Arul M.

    2014-01-01

    Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here, we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyze 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumors without known driver mutations. In addition, we observe exon skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations. PMID:25531467

  9. Comparing jack pine slash and forest floor moisture contents and National Fire Danger Rating System predictions.

    Treesearch

    Robert M. Loomis; William A. Main

    1980-01-01

    Relations between certain slash and forest floor moisture contents and the applicable estimated time lag fuel moistures of the National Fire Danger Rating System were investigated for 1-year-old jack pine fuel types in northeastern Minnesota and central Lower Michigan. Only approximate estimates of actual fuel moisture are possible fore the relations determined, thus...

  10. Seed source variation in tracheid length and specific gravity of five-year-old jack pine seedlings

    Treesearch

    James P. King

    1968-01-01

    Jack pine (Pinus banksiana Lamb.) is widely used in Lake States reforestation because of its ability to make rapid early growth on relatively infertile sites. It is a major pulpwood producing species. Since the quality and yield of pulp are so strongly influenced by tracheid length and specific gravity, information on genetic variation in these...

  11. The Future of the American Faculty: An Interview with Martin J. Finkelstein and Jack H. Schuster

    ERIC Educational Resources Information Center

    Rice, R. Eugene

    2004-01-01

    Martin J. Finkelstein and Jack H. Schuster have teamed up to continue tracing the changes taking place in faculty work with their Project on the American Faculty. They have published The New Academic Generation: A Profession in Transformation (1998), co-authored with Robert Seal, and are preparing a new manuscript to appear in 2004 with a working…

  12. Was Jack the Ripper a Slaughterman? Human-Animal Violence and the World’s Most Infamous Serial Killer

    PubMed Central

    Knight, Andrew; Watson, Katherine D.

    2017-01-01

    Simple Summary The identity of Jack the Ripper remains one of the greatest unsolved crime mysteries in history. Jack was notorious both for the brutality of his murders and also for his habit of stealing organs from his victims. His speed and skill in doing so, in conditions of poor light and haste, fueled theories he was a surgeon. However, re-examination of a mortuary sketch from one of his victims has revealed several key aspects that strongly suggest he had no professional surgical training. Instead, the technique used was more consistent with that of a slaughterhouse worker. There were many small-scale slaughterhouses in East London in the 1880s, within which conditions were harsh for animals and workers alike. The brutalizing effects of such work only add to concerns highlighted by modern research that those who commit violence on animals are more likely to target people. Modern slaughterhouses are more humane in some ways but more desensitizing in others, and sociological research has indicated that communities with slaughterhouses are more likely to experience the most violent of crimes. The implications for modern animal slaughtering, and our social reliance on slaughterhouses, are explored. Abstract Hundreds of theories exist concerning the identity of “Jack the Ripper”. His propensity for anatomical dissection with a knife—and in particular the rapid location and removal of specific organs—led some to speculate that he must have been surgically trained. However, re-examination of a mortuary sketch of one of his victims has revealed several aspects of incisional technique highly inconsistent with professional surgical training. Related discrepancies are also apparent in the language used within the only letter from Jack considered to be probably authentic. The techniques he used to dispatch his victims and retrieve their organs were, however, highly consistent with techniques used within the slaughterhouses of the day. East London in the 1880s had

  13. Ecological Responses to Five Years of Experimental Nitrogen Application in an Upland Jack-pine Stand

    NASA Astrophysics Data System (ADS)

    Melaschenko, N.; Berryman, S.; Straker, J.; Berg, K.; McDonough, A.; Watmough, S. A.

    2016-12-01

    A five-year experimental study was conducted to evaluate the response of an upland jack-pine (Pinus banksiana) forest to elevated levels of nitrogen (N) deposition in Northern Alberta. N deposition in the region is expected to increase with industrial expansion of oil sands activity, and there is regional interest to set N critical loads for sensitive ecosystems. In this study, N was applied as NH4NO3 above a jack-pine canopy via helicopter, annually for five years (2010-2015) at dosages equivalent to 5, 10, 15, 20 and 25 kg N ha-1 yr-1. Approximately 35% of the applied N was retained in the canopy while 65% reached understory vegetation dominated by lichens and mosses. We measured a significant increase in tissue N concentrations of common ground lichens (Cladonia mitis and C. stellaris) and ground moss (Pleurozium schreberi) as well as epiphytic lichens (Hypogymnia physodes and Evernia mesomorpha). On an annual basis, the applied N was primarily captured in the lichen and moss understory, dominated by C. mitis. In the highest treatments, N concentrations in C. mitis were 1.5-2.5 times greater than pre-treatment values. Peak N concentrations in the ground moss Pleurozium schreberi (1.4%) indicate that a threshold of N saturation was reached by year 3. We observed no changes in community composition of vascular and non-vascular plants, or changes in vascular plant tissue N. Chlorophyll levels in C. mitis increased with N treatment, but there was no indication of toxicity or changes to decomposition and growth. After five years of N application, only Peltigera polydactylon, a ground cyanolichen, appeared to be negatively impacted where the thalli showed necrosis at deposition loads >10kg N ha-1 yr-1. No changes to biomass or N ecosystem processes were observed. Based on these observations, we provide evidence that the first adverse ecological effects of N deposition in jack-pine stands occurred at deposition rates of 10 kg N ha-1 yr-1.

  14. Variability and persistence of post-fire biological legacies in jack pine-dominated ecosystems of northern Lower Michigan

    Treesearch

    Daniel Kashian; Gregory Corace; Lindsey Shartell; Deahn M. Donner; Philip Huber

    2011-01-01

    Stand-replacing wildfires have historically shaped the forest structure of dry, sandy jack pine-dominated ecosystems at stand and landscape scales in northern Lower Michigan. Unique fire behavior during large wildfire events often preserves long strips of unburned trees arranged perpendicular to the direction of fire spread. These biological legacies create...

  15. Variability and persistence of post-fire biological legacies in jack pine-dominated ecosystems of northern Lower Michigan

    Treesearch

    Daniel M. Kashian; R. Gregory Corace; Lindsey M. Shartell; Deahn M. Donner; Philip W. Huber

    2012-01-01

    On the dry, flat, jack pine (Pinus banksiana Lamb.)-dominated ecosystems of the northern Lake States and eastern Canada, wildfire behavior often produces narrow, remnant strips of unburned trees that provide heterogeneity on a landscape historically shaped by stand-replacing wildfires. We used landscape metrics to analyze a chronosequence of aerial...

  16. We Are All in the Dumps with Jack and Guy: Two Nursery Rhymes with Pictures by Maurice Sendak.

    ERIC Educational Resources Information Center

    Neumeyer, Peter F.

    1994-01-01

    Describes and critiques Maurice Sendak's newest book, "We Are All in the Dumps with Jack and Guy," which includes nursery rhymes and pictures. Relates Sendak's book to the poetry of William Blake. Suggests possible readings for the book and approaches to teaching it. (HB)

  17. What can volunteer angler tagging data tell us about the status of the Giant Trevally (ulua aukea) Caranx ignobilis fishery in Hawaii: revisiting data collected during Hawaii’s Ulua and Papio Tagging Project 2000-2016

    USGS Publications Warehouse

    Grabowski, Timothy B.; Franklin, Erik C.

    2017-01-01

    Giant Trevally (ulua aukea) Caranx ignobilis is one of the most highly prized and frequentlytargeted nearshore species. However, there is very little information on its current status inHawaiian waters. This study uses mark-recapture data collected as part of recreational anglertagging program conducted by the Hawaii Department of Land and Natural Resources-Divisionof Aquatic Resources during 2000-2012. Mark-recapture data were used to estimate vonBertalanffy growth curve parameters and survivorship. Growth curves generated from the markrecapturedata suggested that Giant Trevally from the main Hawaiian Islands may be growingfaster and reach a smaller maximum size than individuals in the Northwest Hawaiian Islands, butthere are a number of issues rendering this conclusion uncertain. The survivorship of GiantTrevally was positively associated with age, in part due to ontogenetic habitat shifts that result inolder fish moving to offshore habitats where they are less vulnerable to anglers. When comparedto stock assessments performed using commercial landings data and fisheries-independent visualsurveys, the mark-recapture data produced similar estimates for the average length of exploitedfish, a metric highly negatively correlated to fishing mortality. These results emphasize the needfor additional information on the biology of Giant Trevally in Hawaiian waters and suggest thatthe data collected from this recreational angler tagging program may be useful to generatereliable estimates of mortality for stock assessment purposes.

  18. Recovering the primary geochemistry of Jack Hills zircons through quantitative estimates of chemical alteration

    NASA Astrophysics Data System (ADS)

    Bell, Elizabeth A.; Boehnke, Patrick; Harrison, T. Mark

    2016-10-01

    Despite the robust nature of zircon in most crustal and surface environments, chemical alteration, especially associated with radiation damaged regions, can affect its geochemistry. This consideration is especially important when drawing inferences from the detrital record where the original rock context is missing. Typically, alteration is qualitatively diagnosed through inspection of zircon REE patterns and the style of zoning shown by cathodoluminescence imaging, since fluid-mediated alteration often causes a flat, high LREE pattern. Due to the much lower abundance of LREE in zircon relative both to other crustal materials and to the other REE, disturbance to the LREE pattern is the most likely first sign of disruption to zircon trace element contents. Using a database of 378 (148 new) trace element and 801 (201 new) oxygen isotope measurements on zircons from Jack Hills, Western Australia, we propose a quantitative framework for assessing chemical contamination and exchange with fluids in this population. The Light Rare Earth Element Index is scaled on the relative abundance of light to middle REE, or LREE-I = (Dy/Nd) + (Dy/Sm). LREE-I values vary systematically with other known contaminants (e.g., Fe, P) more faithfully than other suggested proxies for zircon alteration (Sm/La, various absolute concentrations of LREEs) and can be used to distinguish primary compositions when textural evidence for alteration is ambiguous. We find that zircon oxygen isotopes do not vary systematically with placement on or off cracks or with degree of LREE-related chemical alteration, suggesting an essentially primary signature. By omitting zircons affected by LREE-related alteration or contamination by mineral inclusions, we present the best estimate for the primary igneous geochemistry of the Jack Hills zircons. This approach increases the available dataset by allowing for discrimination of on-crack analyses (and analyses with ambiguous or no information on spot placement or

  19. A kinetic study of jack-bean urease denaturation by a new dithiocarbamate bismuth compound

    NASA Astrophysics Data System (ADS)

    Menezes, D. C.; Borges, E.; Torres, M. F.; Braga, J. P.

    2012-10-01

    A kinetic study concerning enzymatic inhibitory effect of a new bismuth dithiocarbamate complex on jack-bean urease is reported. A neural network approach is used to solve the ill-posed inverse problem arising from numerical treatment of the subject. A reaction mechanism for the urease denaturation process is proposed and the rate constants, relaxation time constants, equilibrium constants, activation Gibbs free energies for each reaction step and Gibbs free energies for the transition species are determined.

  20. Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin

    PubMed Central

    Tan, Lirong; Su, Jiyan; Wu, Dianwei; Yu, Xiaodan; Su, Zuqing; Wu, Xiaoli; Kong, Songzhi; Lai, Xiaoping; Lin, Ji; Su, Ziren

    2013-01-01

    Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50 of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of K i = 3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant of K i* = 1.47 × 10−4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases. PMID:24198731

  1. Multi-function magnetic jack control drive mechanism

    DOEpatents

    Bollinger, L.R.; Crawford, D.C.

    1983-10-06

    A multi-function magnetic jack control drive mechanism for controlling a nuclear reactor is provided. The mechanism includes an elongate pressure housing in which a plurality of closely spaced drive rods are located. Each drive rod is connected to a rod which is insertable in the reactor core. An electromechanical stationary latch device is provided which is actuatable to hold each drive rod stationary with respect to the pressure housing. An electromechanical movable latch device is also provided for each one of the drive rods. Each movable latch device is provided with a base and is actuatable to hold a respective drive rod stationary with respect to the base. An electromechanical lift device is further provided for each base which is actuatable for moving a respective base longitudinally along the pressure housing. In this manner, one or more drive rods can be moved in the pressure housing by sequentially and repetitively operating the electromechanical devices. Preferably, each latch device includes a pair of opposed latches which grip teeth located on the respective drive rod. Two, three, or four drive rods can be located symmetrically about the longitudinal axis of the pressure housing.

  2. Multi-function magnetic jack control drive mechanism

    DOEpatents

    Bollinger, Lawrence R.; Crawford, Donald C.

    1986-01-01

    A multi-function magnetic jack control drive mechanism for controlling a nuclear reactor is provided. The mechanism includes an elongate pressure housing in which a plurality of closely spaced drive rods are located. Each drive rod is connected to a rod which is insertable in the reactor core. An electromechanical stationary latch device is provided which is actuatable to hold each drive rod stationary with respect to the pressure housing. An electromechanical movable latch device is also provided for each one of the drive rods. Each movable latch device is provided with a base and is actuatable to hold a respective drive rod stationary with respect to the base. An electromechanical lift device is further provided for each base which is actuatable for moving a respective base longitudinally along the pressure housing. In this manner, one or more drive rods can be moved in the pressure housing by sequentially and repetitively operating the electromechanical devices. Preferably, each latch device includes a pair of opposed latches which grip teeth located on the respective drive rod. Two, three, or four drive rods can be located symmetrically about the longitudinal axis of the pressure housing.

  3. Structural basis for Mob1-dependent activation of the core Mst–Lats kinase cascade in Hippo signaling

    DOE PAGES

    Ni, Lisheng; Zheng, Yonggang; Hara, Mayuko; ...

    2015-06-24

    The Mst–Lats kinase cascade is central to the Hippo tumor-suppressive pathway that controls organ size and tissue homeostasis. The adaptor protein Mob1 promotes Lats activation by Mst, but the mechanism remains unknown. Here, we show that human Mob1 binds to autophosphorylated docking motifs in active Mst2. This binding enables Mob1 phosphorylation by Mst2. Phosphorylated Mob1 undergoes conformational activation and binds to Lats1. We determine the crystal structures of phospho-Mst2–Mob1 and phospho-Mob1–Lats1 complexes, revealing the structural basis of both phosphorylation-dependent binding events. Further biochemical and functional analyses demonstrate that Mob1 mediates Lats1 activation through dynamic scaffolding and allosteric mechanisms. Thus, Mob1more » acts as a phosphorylation-regulated coupler of kinase activation by virtue of its ability to engage multiple ligands. We propose that stepwise, phosphorylation-triggered docking interactions of nonkinase elements enhance the specificity and robustness of kinase signaling cascades.« less

  4. Doubletalk: A Literary Pairing of "The Giver" and "We Are All in the Dumps with Jack and Guy."

    ERIC Educational Resources Information Center

    Lehman, Barbara A.; Crook, Patricia R.

    1998-01-01

    Pairs two books that might stimulate children's literary awareness--Lois Lowry's fantasy novel, "The Giver," and Maurice Sendak's picture book, "We Are All in the Dumps with Jack and Guy." Finds that the pairing and comparisons increased understandings about each work and how complementary they really are. (PA)

  5. Differential effects of plant ontogeny and damage type on phloem and foliage monoterpenes in jack pine (Pinus banksiana).

    PubMed

    Erbilgin, Nadir; Colgan, L Jessie

    2012-08-01

    Coniferous trees have both constitutive and inducible defences that deter or kill herbivores and pathogens. We investigated constitutive and induced monoterpene responses of jack pine (Pinus banksiana Lamb.) to a number of damage types: a fungal associate of the mountain pine beetle (Dendroctonus ponderosae Hopkins), Grosmannia clavigera (Robinson-Jeffrey & R.W. Davidson); two phytohormones, methyl jasmonate (MJ) and methyl salicylate (MS); simulated herbivory; and mechanical wounding. We only included the fungal, MJ and mechanical wounding treatments in the field experiments while all treatments were part of the greenhouse studies. We focused on both constitutive and induced responses between juvenile and mature jack pine trees and differences in defences between phloem and needles. We found that phytohormone applications and fungal inoculation resulted in the greatest increase in monoterpenes in both juvenile and mature trees. Additionally, damage types differentially affected the proportions of individual monoterpenes: MJ-treated mature trees had higher myrcene and β-pinene than fungal-inoculated mature trees, while needles of juveniles inoculated with the fungus contained higher limonene than MJ- or MS-treated juveniles. Although the constitutive monoterpenes were higher in the phloem of juveniles than mature jack pine trees, the phloem of mature trees had a much higher magnitude of induction. Further, induced monoterpene concentrations in juveniles were higher in phloem than in needles. There was no difference in monoterpene concentration between phytohormone applications and G. clavigera inoculation in mature trees, while in juvenile trees MJ was different from both G. clavigera and simulated herbivory in needle monoterpenes, but there was no difference between phytohormone applications and simulated herbivory in the phloem.

  6. Effects of a clear-cut harvest on soil respiration in a jack pine - Lichen woodland

    USGS Publications Warehouse

    Striegl, Robert G.; Wickland, K.P.

    1998-01-01

    Quantification of the components of ecosystem respiration is essential to understanding carbon (C) cycling of natural and disturbed landscapes. Soil respiration, which includes autotrophic and heterotrophic respiration from throughout the soil profile, is the second largest flux in the global carbon cycle. We measured soil respiration (soil CO2 emission) at an undisturbed mature jack pine (Pinus banksiana Lamb.) stand in Saskatchewan (old jack pine, OJP), and at a formerly continuous portion of the stand that was clear-cut during the previous winter (clear-cut, CC). Tree harvesting reduced soil CO2 emission from ???22.5 to ???9.1 mol CO2??m2 for the 1994 growing season. OJP was a small net sink of atmospheric CO2, while CC was a net source of CO2. Winter emissions were similar at both sites. Reduction of soil respiration was attributed to disruption of the soil surface and to the death of tree roots. Flux simulations for CC and OJP identify 40% of CO2 emission at the undisturbed OJP site as near-surface respiration, 25% as deep-soil respiration, and 35% as tree-root respiration. The near-surface component was larger than the estimated annual C input to soil, suggesting fast C turnover and no net C accumulation in these boreal uplands in 1994.

  7. Sneaker "jack" males outcompete dominant "hooknose" males under sperm competition in Chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Young, Brent; Conti, David V; Dean, Matthew D

    2013-12-01

    In a variety of taxa, males deploy alternative reproductive tactics to secure fertilizations. In many species, small "sneaker" males attempt to steal fertilizations while avoiding encounters with larger, more aggressive, dominant males. Sneaker males usually face a number of disadvantages, including reduced access to females and the higher likelihood that upon ejaculation, their sperm face competition from other males. Nevertheless, sneaker males represent an evolutionarily stable strategy under a wide range of conditions. Game theory suggests that sneaker males compensate for these disadvantages by investing disproportionately in spermatogenesis, by producing more sperm per unit body mass (the "fair raffle") and/or by producing higher quality sperm (the "loaded raffle"). Here, we test these models by competing sperm from sneaker "jack" males against sperm from dominant "hooknose" males in Chinook salmon. Using two complementary approaches, we reject the fair raffle in favor of the loaded raffle and estimate that jack males were ∼1.35 times as likely as hooknose males to fertilize eggs under controlled competitive conditions. Interestingly, the direction and magnitude of this skew in paternity shifted according to individual female egg donors, suggesting cryptic female choice could moderate the outcomes of sperm competition in this externally fertilizing species.

  8. Detrital Zircons From the Jack Hills and Mount Narryer, Western Australia: Geochronological, Morphological, and Geochemical Evidence for Diverse >4000 Ma Source Rocks

    NASA Astrophysics Data System (ADS)

    Crowley, J. L.; Myers, J. S.; Sylvester, P. J.; Cox, R. A.

    2004-05-01

    Detrital zircons from all major clastic units in the Jack Hills and Mount Narryer metasedimentary belts, Western Australia, were analyzed for morphology, internal zoning, inclusion mineralogy, age, and trace element concentrations (latter two obtained by laser-ablation microprobe ICPMS). The results show that zircons were derived from a wide diversity of rocks, including previously described, >4000 Ma grains that are older than any known terrestrial rocks. In three metaconglomerate samples from the western Jack Hills, 4200-3800 Ma zircons ("old grains") comprise 14% of the population, 3800-3600 Ma grains form only 2%, and 3550-3250 Ma zircons ("young grains") are dominant with a significant peak at 3380 Ma. Old and young grains are interpreted as being from similar rock types because they are indistinguishable in trace element concentrations, size (several hundred microns), morphology (subequant, typically fragmented), internal zoning (typically both oscillatory and sector), and U concentration (50-200 ppm). Many of these properties suggest an intermediate plutonic source, whereas an evolved granitic source was previously interpreted from rare-earth element and oxygen isotope data. Detrital zircons in quartzites and metaconglomerates at Mount Narryer differ significantly from zircons from the western Jack Hills. Old grains comprise only 3% (most of which are 4200-4100 Ma), 3800-3600 Ma zircons form 31%, and there are peaks at 3650, 3600, and 3500 Ma. Old and young grains have similar properties that suggest granitic sources, such as elongate prismatic morphology, oscillatory zoning, high U concentrations (100-600 ppm), and xenotime and monazite inclusions. Trace element concentrations are broadly similar to those in Jack Hills zircons, with notable exceptions being generally higher U, smaller Ce and Eu anomalies, and lower Nb/Ta. It is considered unlikely that Jack Hills zircons were derived from granitic gneisses that surround the metasedimentary belts because

  9. Jack Michael's Appointments at the University of Houston and Arizona State University: Reflections from a Former Student

    ERIC Educational Resources Information Center

    Mabry, John H.

    2016-01-01

    Jack Michael was an early enthusiast for what is now called applied behavior analysis. His many seminal contributions were through early publications in applied behavior analysis and the work of the students he trained (e.g., T. Ayllon, M. M. Wolf). His close mentorship of students earned him acclaim as a teacher along with his many theoretical…

  10. Survival and growth of two intensively cultured jack pine provenances raised in Tubepak and Jiffy 7 containers

    Treesearch

    J. Zavitkovski; Howard M. Phipps

    1983-01-01

    Container type, provenance, and spacing affect survival, height and d.b.h, growth, and biomass production of intensively cultured jack pine. The Lower Michigan provenance and Tubepak grown plants performed better than the local (Wisconsin) provenance and plants raised in Jiffy 7 pellets. At age 5, biomass of Tubepak plantings was more than 100% higher than that of...

  11. Displacement effects of heavy human use on coral reef predators within the Molokini Marine Life Conservation District.

    PubMed

    Filous, Alexander; Friedlander, Alan M; Koike, Haruko; Lammers, Marc; Wong, Adam; Stone, Kristy; Sparks, Russell T

    2017-08-15

    The impact of marine ecotourism on reef predators is poorly understood and there is growing concern that overcrowding in Marine Protected Areas (MPAs) may disturb the species that these areas were established to protect. To improve our understanding of this issue, we used acoustic telemetry to examine the relationship between human activity at the Molokini Marine Life Conservation District (MLCD) and the habitat use of five reef-associated predators (Caranx melampygus, Caranx ignobilis, Triaenodon obesus, Carcharhinus amblyrhynchos, and Aprion virscens). During peak hours of human use, there was a negative relationship (R 2 =0.77, P<0.001) between the presence of bluefin trevally (Caranx melampygus) and vessels in subzone A. No other species showed strong evidence of this relationship. However, our results suggest that during this time, the natural ecosystem function that the reserve was established to protect may be compromised and overcrowding should be considered when managing MPAs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Finite elements analysis of an underground collector installed by pipe-jacking method

    NASA Astrophysics Data System (ADS)

    María Díaz-Díaz, Luis; Omer, Joshua; Arias, Daniel; Pando, Luis

    2016-04-01

    This study presents a useful analysis method for estimating simultaneously the stability, stress distribution and groundwater seepage as micro - tunnel is being advanced into the ground. The research is mainly concerned with the results of a case study conducted on a project to create a long industrial collector of effluent network in the east bank of the river Avilés (north coast of Spain). This coastal city has significant port and industrial installations in its environs. The geology of the location comprises Quaternary deposits on both flanks of the estuary and includes different highly variable geotechnical behavior. The industrial effluent network, constructed in the year 2010, has a length of 13.087 km and consists of 1.5 m diameter pipes, reaching a maximum depth of 5.8 m below the surface. Only the first 7.0 km of the collector (south area) were formed using pipe-jacking method whilst the rest were formed in open excavations or surface laid. Using the commercial software RS2, a 2D finite element program for soil and rock application, the ground response to pipe jacking in pipeline installation in Avilés was analyzed. Both axi-symmetric and plane strain analyses were carried out in RS2 to simulate in 3D the ground response to pipe advancement. The results demonstrate how much of deformation there is at ground surface in the immediate vicinity of the pipeline. The main objective is to show the possible patterns of ground subsidence and tunnel stresses to inform designers as to whether the tunnel will be stable and safe.

  13. On the Eicosanoid Trail with John Vane and Jack McGiff: 1974-1976. A personal reminiscence.

    PubMed

    Flower, R J

    2015-07-01

    In this brief personal reminiscence I comment upon the friendship and mutual understanding that arose between two great scientists and co-travellers, John Vane and Jack McGiff. I relate the events that led up to their meeting and focus on the brief period of time when they worked together on eicosanoid pharmacology in the UK. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Effect of average growing season temperature on seedling germination, survival and growth in jack pine (Pinus banksiana Lamb.)

    Treesearch

    A. David; E. Humenberger

    2017-01-01

    Because jack pine (Pinus banksiana Lamb.) is serotinous, it retains multiple years of cones until environmental conditions are favorable for releasing seed. These cones, which contain seed cohorts that developed under a variety of growing seasons, can be accurately aged using bud scale scars on twigs and branches. By calculating the average daily...

  15. Analysis of the car body stability performance after coupler jack-knifing during braking

    NASA Astrophysics Data System (ADS)

    Guo, Lirong; Wang, Kaiyun; Chen, Zaigang; Shi, Zhiyong; Lv, Kaikai; Ji, Tiancheng

    2018-06-01

    This paper aims to improve car body stability performance by optimising locomotive parameters when coupler jack-knifing occurs during braking. In order to prevent car body instability behaviour caused by coupler jack-knifing, a multi-locomotive simulation model and a series of field braking tests are developed to analyse the influence of the secondary suspension and the secondary lateral stopper on the car body stability performance during braking. According to simulation and test results, increasing secondary lateral stiffness contributes to limit car body yaw angle during braking. However, it seriously affects the dynamic performance of the locomotive. For the secondary lateral stopper, its lateral stiffness and free clearance have a significant influence on improving the car body stability capacity, and have less effect on the dynamic performance of the locomotive. An optimised measure was proposed and adopted on the test locomotive. For the optimised locomotive, the lateral stiffness of secondary lateral stopper is increased to 7875 kN/m, while its free clearance is decreased to 10 mm. The optimised locomotive has excellent dynamic and safety performance. Comparing with the original locomotive, the maximum car body yaw angle and coupler rotation angle of the optimised locomotive were reduced by 59.25% and 53.19%, respectively, according to the practical application. The maximum derailment coefficient was 0.32, and the maximum wheelset lateral force was 39.5 kN. Hence, reasonable parameters of secondary lateral stopper can improve the car body stability capacity and the running safety of the heavy haul locomotive.

  16. Applying the vantage PDMS to jack-up drilling ships

    NASA Astrophysics Data System (ADS)

    Yin, Peng; Chen, Yuan-Ming; Cui, Tong-Kai; Wang, Zi-Shen; Gong, Li-Jiang; Yu, Xiang-Fen

    2009-09-01

    The plant design management system (PDMS) is an integrated application which includes a database and is useful when designing complex 3-D industrial projects. It could be used to simplify the most difficult part of a subsea oil extraction project—detailed pipeline design. It could also be used to integrate the design of equipment, structures, HVAC, E-ways as well as the detailed designs of other specialists. This article mainly examines the applicability of the Vantage PDMS database to pipeline projects involving jack-up drilling ships. It discusses the catalogue (CATA) of the pipeline, the spec-world (SPWL) of the pipeline, the bolt tables (BLTA) and so on. This article explains the main methods for CATA construction as well as problem in the process of construction. In this article, the authors point out matters needing attention when using the Vantage PDMS database in the design process and discuss partial solutions to these questions.

  17. Characterization of inclusions in terrestrial impact formed zircon: Constraining the formation conditions of Hadean zircon from Jack Hills, Western Australia

    NASA Astrophysics Data System (ADS)

    Faltys, J. P.; Wielicki, M. M.; Sizemore, T. M.

    2017-12-01

    Due to the discovery and subsequent geochemical analysis of Hadean terrestrial material (e.g. detrital zircon from Jack Hills, Western Australia), a dramatic paradigm shift has occurred in the hypothesized near surface conditions of the first 500 million years of Earth's evolution. From a hellish setting riddled with impactors and not fit for life to a much milder environment that may have been uniquely suitable for the origin of life. Geochemical analyses of these ancient materials have been used to suggest the presence of water at or near the surface as well as the existence of continental crust during the Hadean, both of which have been suggested as necessary for the origin of life. However, the intensity of extraterrestrial bombardment during the Hadean and the effects of such events on the origin of life remains poorly understood. Clearly, as evidenced by Phanerozoic impact events, extraterrestrial impactors have the potential to dramatically effect the environment, particularly the biosphere. Early Earth likely experienced multiple large impact events, as evidenced by the lunar record, however whether those impacts were sufficient to frustrate the origin of life remains an open question. Although multiple lines of evidence, including the inclusion population, suggest the formation of Hadean zircon from Jack Hills as crystallizing in an under-thrust environment from S-type magmas, a recent study has suggested their formation in an impact melt environment analogous to a portion of the Sudbury Igneous Complex at the Sudbury impact structure. To determine between these two formation scenarios we have under-taken an inclusion study of terrestrial impact formed zircon from four of the largest terrestrial impact structures (Sudbury, Canada; Manicouagan, Canada; Vredefort, South Africa; Morokweng, South Africa), to compare to the vast inclusion dataset that exists for Jack Hills zircon. Preliminary data suggests a different inclusion population, from Hadean zircon

  18. Zn uptake, physiological response and stress attenuation in mycorrhizal jack bean growing in soil with increasing Zn concentrations.

    PubMed

    Andrade, Sara A L; Gratão, Priscila L; Schiavinato, Marlene A; Silveira, Adriana P D; Azevedo, Ricardo A; Mazzafera, Paulo

    2009-06-01

    The influence of arbuscular mycorrhizal fungi (AMF) inoculation on Canavalia ensiformis growth, nutrient and Zn uptake, and on some physiological parameters in response to increasing soil Zn concentrations was studied. Treatments were applied in seven replicates in a 2 x 4 factorial design, consisting of the inoculation or not with the AMF Glomus etunicatum, and the addition of Zn to soil at the concentrations of 0, 100, 300 and 900 mg kg(-1). AMF inoculation enhanced the accumulation of Zn in tissues and promoted biomass yields and root nodulation. Mycorrhizal plants exhibited relative tolerance to Zn up to 300 mg kg(-1) without exhibiting visual symptoms of toxicity, in contrast to non-mycorrhizal plants which exhibited a significant growth reduction at the same soil Zn concentration. The highest concentration of Zn added to soil was highly toxic to the plants. Leaves of plants grown in high Zn concentration exhibited a Zn-induced proline accumulation and also an increase in soluble amino acid contents; however proline contents were lower in mycorrhizal jack beans. Plants in association or not with the AMF exhibited marked differences in the foliar soluble amino acid profile and composition in response to Zn addition to soil. In general, Zn induced oxidative stress which could be verified by increased lipid peroxidation rates and changes in catalase, ascorbate peroxidase, glutathione reductase and superoxide dismutase activities. In summary, G. etunicatum was able to maintain an efficient symbiosis with jack bean plants in moderately contaminated Zn-soils, improving plant performance under those conditions, which is likely to be due to a combination of physiological and nutritional changes caused by the intimate relation between fungus and plant. The enhanced Zn uptake by AMF inoculated jack bean plants might be of interest for phytoremediation purposes.

  19. Using airborne HIAPER Pole-to-Pole Observations (HIPPO) to evaluate model and remote sensing estimates of atmospheric carbon dioxide

    NASA Astrophysics Data System (ADS)

    Frankenberg, Christian; Kulawik, Susan S.; Wofsy, Steven C.; Chevallier, Frédéric; Daube, Bruce; Kort, Eric A.; O'Dell, Christopher; Olsen, Edward T.; Osterman, Gregory

    2016-06-01

    In recent years, space-borne observations of atmospheric carbon dioxide (CO2) have been increasingly used in global carbon-cycle studies. In order to obtain added value from space-borne measurements, they have to suffice stringent accuracy and precision requirements, with the latter being less crucial as it can be reduced by just enhanced sample size. Validation of CO2 column-averaged dry air mole fractions (XCO2) heavily relies on measurements of the Total Carbon Column Observing Network (TCCON). Owing to the sparseness of the network and the requirements imposed on space-based measurements, independent additional validation is highly valuable. Here, we use observations from the High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Pole-to-Pole Observations (HIPPO) flights from 01/2009 through 09/2011 to validate CO2 measurements from satellites (Greenhouse Gases Observing Satellite - GOSAT, Thermal Emission Sounder - TES, Atmospheric Infrared Sounder - AIRS) and atmospheric inversion models (CarbonTracker CT2013B, Monitoring Atmospheric Composition and Climate (MACC) v13r1). We find that the atmospheric models capture the XCO2 variability observed in HIPPO flights very well, with correlation coefficients (r2) of 0.93 and 0.95 for CT2013B and MACC, respectively. Some larger discrepancies can be observed in profile comparisons at higher latitudes, in particular at 300 hPa during the peaks of either carbon uptake or release. These deviations can be up to 4 ppm and hint at misrepresentation of vertical transport. Comparisons with the GOSAT satellite are of comparable quality, with an r2 of 0.85, a mean bias μ of -0.06 ppm, and a standard deviation σ of 0.45 ppm. TES exhibits an r2 of 0.75, μ of 0.34 ppm, and σ of 1.13 ppm. For AIRS, we find an r2 of 0.37, μ of 1.11 ppm, and σ of 1.46 ppm, with latitude-dependent biases. For these comparisons at least 6, 20, and 50 atmospheric soundings have been averaged for GOSAT, TES, and AIRS

  20. Automated detection and mapping of crown discolouration caused by jack pine budworm with 2.5 m resolution multispectral imagery

    NASA Astrophysics Data System (ADS)

    Leckie, Donald G.; Cloney, Ed; Joyce, Steve P.

    2005-05-01

    Jack pine budworm ( Choristoneura pinus pinus (Free.)) is a native insect defoliator of mainly jack pine ( Pinus banksiana Lamb.) in North America east of the Rocky Mountains. Periodic outbreaks of this insect, which generally last two to three years, can cause growth loss and mortality and have an important impact ecologically and economically in terms of timber production and harvest. The jack pine budworm prefers to feed on current year needles. Their characteristic feeding habits cause discolouration or reddening of the canopy. This red colouration is used to map the distribution and intensity of defoliation that has taken place that year (current defoliation). An accurate and consistent map of the distribution and intensity of budworm defoliation (as represented by the red discolouration) at the stand and within stand level is desirable. Automated classification of multispectral imagery, such as is available from airborne and new high resolution satellite systems, was explored as a viable tool for objectively classifying current discolouration. Airborne multispectral imagery was acquired at a 2.5 m resolution with the Multispectral Electro-optical Imaging Sensor (MEIS). It recorded imagery in six nadir looking spectral bands specifically designed to detect discolouration caused by budworm and a near-infrared band viewing forward at 35° was also used. A 2200 nm middle infrared image was acquired with a Daedalus scanner. Training and test areas of different levels of discolouration were created based on field observations and a maximum likelihood supervized classification was used to estimate four classes of discolouration (nil-trace, light, moderate and severe). Good discrimination was achieved with an overall accuracy of 84% for the four discolouration levels. The moderate discolouration class was the poorest at 73%, because of confusion with both the severe and light classes. Accuracy on a stand basis was also good, and regional and within stand

  1. Jack Rabbit Pretest Shadowplate Drawings For TATB IHE Model Development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hart, M M; McDaniel, D W

    The Jack Rabbit Pretest (PT) series consisted of 5 focused hydrodynamic experiments 2021E PT3, PT4, PT5, PT6, and PT7. They were fired in March and April of 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory, Livermore, California. These experiments measured deadzone formation and impulse gradients created during the detonation of TATB based insensitive high explosive. When setting up computer simulations of the Jack Rabbit Pretest series, the modeler or code developer can execute simulations with increasing degrees of refinement using detail found in the shadowplate design. The easiest way to get started is by treating themore » shadowplate in each experiment as a monolithic homogeneous piece of stainless steel. The simulation of detonation would begin as a point initiation below the center, bottom surface of the shadowplate. The detonation running through the ultrafine TATB booster can be simulated using program burn and then switched over to a reactive flow detonation model as the detonation front crosses the boundary into the main charge LX-17 IHE. A modeler wanting to further refine the simulation and progression of shock through the shadowplate can use the more detailed shadowplate design information presented in this document. The source drawings are included in Appendix A of this document. Their titles and drawing numbers are listed. Each experiment's shadowplate consists of two major components. A 303 stainless steel shape that defines the outer dimensions of shadowplate and a cylindrical 303 stainless steel detonator housing that is located in a closely machined pocket in the shape. The SIMPLE ASSY drawing accurately represents the dimensions of the outer shape, it's machined cylindrical pocket, and detonator body which is treated as a monolithic, homogeneous piece of stainless steel. The detonator body cross section shows an accurately dimensioned void where the slapper flyer barrel, LX-16 (pressed PETN) pellet, and

  2. Magic Words, Magic Brush: The Art of William Butler and Jack Yeats. ArtsEdge Curricula, Lessons and Activities.

    ERIC Educational Resources Information Center

    Karsten, Jayne

    This curriculum unit, designed for grades 7-12, integrates various artistic disciplines with geography, history, social studies, media, and technology. This unit on William Butler Yeats, the writer, and Jack Yeats, the painter, seeks to immerse students in a study of the brothers as voices of Ireland and as two of the most renowned artists of the…

  3. Assessment of possible sources of microbiological contamination and water-quality characteristics of the Jacks Fork, Ozark National Scenic Riverways, Missouri; phase II

    USGS Publications Warehouse

    Davis, Jerri V.; Richards, Joseph M.

    2002-01-01

    In 1998, an 8-mile reach of the Jacks Fork was included on Missouri?s list of impaired waters as required by Section 303(d) of the Federal Clean Water Act. The identified pollutant on the Jacks Fork was fecal coliform bacteria. Potential sources of fecal contamination to the Jacks Fork include a wastewater treatment plant; campground pit-toilet or septic-system effluent; a large commercial, cross-country horseback trail riding facility; canoeists, boaters, and tubers; and cows.The U.S. Geological Survey, in cooperation with the National Park Service, conducted a study to better understand the extent and sources of microbiological contamination within the Jacks Fork from Alley Spring to the mouth, which includes the 8-mile 303(d) reach. Identification of the sources would provide the National Park Service and the State of Missouri with the information needed to craft a solution of abatement, regulation, prevention, and mitigation with the end result being the removal of the Jacks Fork from the 303(d) list. Fifteen sites were sampled from November 1999 through December 2000. An additional site was sampled one time. Samples were collected mostly during base-flow conditions during a variety of nonrecreational and recreational season river uses. Samples were analyzed for selected fecal indicator bacteria, physical properties, nutrients, and wastewater organic compounds. During the sampling period, the whole-body-contact recreation standard for fecal coliform (200 colonies per 100 milliliters of sample) was exceeded at three sites on August 10, 2000, and also at one site on May 11, June 7, and October 3, 2000. Fecal coliform densities and instantaneous loads generally increased from background concentrations at the Eminence site, peaked about 2 river miles downstream, and then decreased until the most downstream site sampled. Generally, the largest densities and loads at sites downstream from Eminence not related to wet-weather flow were observed during a trail ride held

  4. BOREAS RSS-4 1994 Southern Study Area Jack Pine LAI and FPAR Data

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Plummer, Stephen

    2000-01-01

    The RSS-4 team collected several data sets related to leaf, plant, and stand physical, optical, and chemical properties. This data set contains leaf area indices and FPAR measurements that were taken at the three conifer sites in the BOREAS SSA during August 1993 and at the jack pine tower flux and a subset of auxiliary sites during July and August 1994. The measurements were made with LAI-2000 and Ceptometer instruments. The measurements were taken for the purpose of model parameterization and to test empirical relationships that were hypothesized between biophysical parameters and remotely sensed data. The data are stored in tabular ASCII files.

  5. Analysis of ITER NbTi and Nb3Sn CICCs experimental minimum quench energy with JackPot, MCM and THEA models

    NASA Astrophysics Data System (ADS)

    Bagni, T.; Duchateau, J. L.; Breschi, M.; Devred, A.; Nijhuis, A.

    2017-09-01

    Cable-in-conduit conductors (CICCs) for ITER magnets are subjected to fast changing magnetic fields during the plasma-operating scenario. In order to anticipate the limitations of conductors under the foreseen operating conditions, it is essential to have a better understanding of the stability margin of magnets. In the last decade ITER has launched a campaign for characterization of several types of NbTi and Nb3Sn CICCs comprising quench tests with a singular sine wave fast magnetic field pulse and relatively small amplitude. The stability tests, performed in the SULTAN facility, were reproduced and analyzed using two codes: JackPot-AC/DC, an electromagnetic-thermal numerical model for CICCs, developed at the University of Twente (van Lanen and Nijhuis 2010 Cryogenics 50 139-148) and multi-constant-model (MCM) (Turck and Zani 2010 Cryogenics 50 443-9), an analytical model for CICCs coupling losses. The outputs of both codes were combined with thermal, hydraulic and electric analysis of superconducting cables to predict the minimum quench energy (MQE) (Bottura et al 2000 Cryogenics 40 617-26). The experimental AC loss results were used to calibrate the JackPot and MCM models and to reproduce the energy deposited in the cable during an MQE test. The agreement between experiments and models confirm a good comprehension of the various CICCs thermal and electromagnetic phenomena. The differences between the analytical MCM and numerical JackPot approaches are discussed. The results provide a good basis for further investigation of CICC stability under plasma scenario conditions using magnetic field pulses with lower ramp rate and higher amplitude.

  6. [Ichthyofauna of the Navidad Bay, Jalisco, México].

    PubMed

    Aguilar-Palomino, B; Pérez Reyes, C; Galván-Magaña, F; Abitía-Cardenas, L A

    2001-03-01

    A check-list and the relative abundance of the ichthyofauna from Bahia de Navidad, Jalisco, Mexico is presented. This poorly known area of the eastern Tropical Pacific ocean is characterized by its great fish diversity. A total of 245 fish species (163 genera, 72 families) were collected during the 1994-1995 annual cycle. Vouchers were deposited in Centro de Ecologia Costera, Universidad de Guadalajara. The most important families in number of species were Carangidae (20 species), Haemulidae (20), Serranidae (17), Sciaenidae (13) and Lutjanidae (8); 20 species represented 85% and 80% of relative abundance and biomass respectively. Microlepidotus brevipinnis, Caranx caninus, Caranx caballus, Kiphosus analogus and Caranx sexfasciatus, were the dominant species. Most fish species collected in Bahia de Navidad have zoogeographical affinity with the Panamic Province (65%), and in lesser proportion with the Eastern Pacific Ocean (19%), Circumtropical (7%), Mexican Province (5%), Indo-Pacific Ocean (3%) and Gulf of California (0.4%). The great ichthyological affinity between the study area and the southern Gulf of California suggests an extension of the of Gulf southern limit.

  7. Mercury contamination in freshwater, estuarine, and marine fishes in relation to small-scale gold mining in Suriname, South America.

    PubMed

    Mol, J H; Ramlal, J S; Lietar, C; Verloo, M

    2001-06-01

    . High mercury concentrations were found in the shark Mustelus higmani (0.71 microg x g(-1)), the crevalle jack Caranx hippos (1.17 microg x g(-1)), and the barracuda Sphyraena guachancho (0.39 microg x g(-1)), but also in nonpiscivorous species such as Calamus bajonado (0.54 microg x g(-1)), Haemulon plumieri (0.47 microg x g(-1)), and Isopisthus parvipinnis (0.48 microg x g(-1)). Mercury levels were positively correlated with the length of the fish in populations of the freshwater piscivores S. rhombeus, Hoplias malabaricus, and Plagioscion squamosissimus, in estuarine species (Arius couma, Cynoscion virescens, and Macrodon ancylodon), and in S. guachancho from the Atlantic Ocean. Copyright 2001 Academic Press.

  8. Effects of soil temperature and elevated atmospheric CO2 concentration on gas exchange, in vivo carboxylation and chlorophyll fluorescence in jack pine and white birch seedlings.

    PubMed

    Zhang, Shouren; Dang, Qing-Lai

    2005-05-01

    One-year-old jack pine (Pinus banksiana Lamb.) and current-year white birch (Betula papyrifera Marsh.) seedlings were grown in ambient (360 ppm) or twice ambient (720 ppm) atmospheric CO2 concentration ([CO2]) and at three soil temperatures (Tsoil = 7, 17 and 27 degrees C initially, increased to 10, 20 and 30 degrees C two months later, respectively) in a greenhouse for 4 months. In situ foliar gas exchange, in vivo carboxylation characteristics and chlorophyll fluorescence were measured after 2.5 and 4 months of treatment. Low Tsoil suppressed net photosynthetic rate (Pn), stomatal conductance (g(s)) and transpiration rate (E) in jack pine in both CO2 treatments and g(s) and E in white birch in ambient [CO2], but enhanced instantaneous water-use efficiency (IWUE) in both species after 2.5 months of treatment. Treatment effects on g(s) and E remained significant throughout the 4-month study. Low Tsoil reduced maximal carboxylation rate (Vcmax) and PAR-saturated electron transport rate (Jmax) in jack pine in elevated [CO2] after 2.5 months of treatment, but not after 4 months of treatment. Low Tsoil increased actual photochemical efficiency of photosystem II (PSII) in the light (DeltaF/Fm') in jack pine, but decreased DeltaF/Fm' in white birch after 4 months of treatment. In response to low Tsoil, photosynthetic linear electron transport to carboxylation (Jc) decreased in jack pine after 2.5 months and in white birch after 4 months of treatment. Low Tsoil increased the ratio of the photosynthetic linear electron transport to oxygenation (Jo) to the total photosynthetic linear electron transport rate through PSII (Jo/J(T)) in both species after 2.5 months of treatment, but the effects became statistically insignificant in white birch after 4 months of treatment. High Tsoil decreased foliar N concentration in white birch. Elevated [CO2] increased Pn, IWUE and Jc but decreased Jo/J(T) in both species at both measurement times except Jc in white birch after 2.5 months

  9. Paleomagnetism of Hadean and Archean Detrital Zircons from the Jack Hills, Western Australia

    NASA Astrophysics Data System (ADS)

    Weiss, B. P.; Lima, E. A.; Alexander, E.; Bell, E. A.; Boehnke, P.; Wielicki, M. M.; Harrison, M.; Fu, R. R.; Kehayias, P.; Glenn, D. R.; Walsworth, R. L.; Araujo, J. F. D.; Einsle, J. F.; Harrison, R.; Trail, D.; Watson, E. B.

    2016-12-01

    Determining the history of Earth's dynamo prior to the oldest known well-preserved rock record is one of the ultimate challenges in the field of paleomagnetism. The dynamo's early history has major implications for the evolution of the core, the initiation of plate tectonics, the physics of magnetic field generation, and the habitability of the early Earth. The only known minerals that might retain paleomagnetic records from well before 3.5 billion years ago (Ga) are detrital zircon crystals found in sedimentary rocks in Western Australia. Ranging up to 4.38 Ga in age, they are the oldest known terrestrial minerals. Tarduno et al. (2015) argued that detrital zircons contain records of an active dynamo dating back to 4.2 Ga. However, it has not been demonstrated that the zircons have escaped remagnetization during the intervening time since their formation (Weiss et al. 2016). Therefore, the age of magnetization in the Jack Hills zircons and the existence of a dynamo prior to 3.5 Ga have yet to be established. To address this issue, we have been studying the magnetism and thermal and aqueous alteration histories of single Archean and Hadean Jack Hills zircon crystals. Peak unblocking temperatures combined with electron backscatter diffraction indicate that the zircons contain inclusions of magnetite and hematite. Electron microscopy, X-ray tomography, and quantum diamond magnetometry indicate that much of the iron oxides in the zircons are associated with cracks and are therefore likely secondary. However, our newly developed Li-in-zircon geospeedometry technique shows for the first time that a small fraction of Hadean zircons retain sharp gradients in Li concentration (see figure), indicating they likely have never heated above the magnetite Curie temperature since their formation at >4 Ga. We describe thermal demagnetization and Thellier-Thellier paleointensity studies of these zircons and implications for the existence of a Hadean dynamo.

  10. Neoarchean metamorphism recorded in high-precision Sm-Nd isotope systematics of garnets from the Jack Hills (Western Australia)

    NASA Astrophysics Data System (ADS)

    Eccles, K. A.; Baxter, E. F.; Mojzsis, S. J.; Marschall, H.; Williams, M. L.; Jercinovic, M. J.

    2013-12-01

    Studies of metasedimentary rocks from the Jack Hills, which host Earth's oldest known detrital minerals, have focused on zircon and occasionally monazite or xenotime, but no attention has been directed toward one of the most common mineral markers of metamorphism: garnet. Garnet can provide a record of the post-depositional, prograde metamorphic history of Archean metasedimentary rocks. Additionally, the use of a newly developed detrital garnet dating technique [1,2] may reveal information about pre-depositional metamorphism that could address lingering questions about the nature and timing of Earth's earliest tectonometamorphic events. Here we investigate garnet from the Jack Hills metasedimentary rocks to test whether they record in situ metamorphism or are a detrital relict of even older metamorphic events. We identified garnet in two bulk quartz-pebble conglomerate samples collected from the 'discovery' outcrop at Eranondoo Hill in the Jack Hills of Western Australia. Electron microprobe analyses of polished grains and SEM measurements of unpolished grain surfaces are consistent, revealing garnet composition indicative of a single generation/population of predominantly almandine-spessartine solid solution (~10-35% mole fraction spessartine). Compositional maps of garnet grains reveal little zoning and no discontinuities, most consistent with a single growth event. Dating Jack Hills' garnet via the Sm-Nd system is possible due to continued development of small sample analysis techniques, including running NdO+ TIMS analyses with Ta2O5 activator [3] permitting <50 ppm 2 sigma analytical precision on a 400pg in-house standard and continued improvement in blanks (<15pg full procedural blanks). Additionally, employing a nondestructive chemical prescreening technique (tabletop SEM) allows for grouping of multiple grains based on chemical similarity. Final Nd loads in the 450-750pg range routinely yield dates with precisions <×10Ma for two point isochrons between

  11. What can zircon ages from the Jack Hills detrital zircon suite really tell us about Hadean geodynamics?

    NASA Astrophysics Data System (ADS)

    Whitehouse, Martin; Nemchin, Alexander

    2015-04-01

    As the only direct sample of the Hadean Earth, detrital zircon grains from the Jack Hills, Western Australia, have been the subject of intense investigation over the almost three decades since their discovery. A wide variety of geochemical and isotopic analyses of these grains, as well as their mineral inclusions, have been used variously to support two fundamentally different models for Hadean geodynamics: (i) Some form of (not necessarily modern-style) plate recycling generating felsic (continental-type?) crust at the boundaries [1, 2], or conversely (ii) the persistence of a long-lived, stagnant basaltic lid within which magmatism occurred as a result of internal temperature perturbations and/or impacts [3, 4], a model also generally consistent with a wide range of observations from post-Hadean geochemical reservoirs. Despite the considerable time and resources expended, the majority of these studies uncritically accept the individual U-Pb zircon ages, even though their veracity is key to many of the interpretations [5, 6]. We report here the results of an in-depth evaluation of all published (and new) U-Pb ages from the Jack Hills zircon suite in order to define age populations that can be used with a high degree of confidence in geodynamic interpretations. A notable problem in the interpretation of U-Pb data from ancient zircon grains (including those as young as the Neoarchean) is that disturbance of the systematics even several 100 Ma after crystallization causes data to spread along the concordia curve without becoming discernably discordant within the relatively large error bounds associated with U/Pb ages from in situ dating methods (e.g. SIMS). While 207Pb/206Pb ages are typically more precise, individually they provide no means to detect Pb-loss-induced younging. However, if two or preferably more analyses have been made in the same zircon growth zone, a reasonable evaluation of the possibility of Pb-loss can be made. In the available Jack Hills zircon

  12. AmeriFlux CA-Qcu Quebec - Eastern Boreal, Black Spruce/Jack Pine Cutover

    DOE Data Explorer

    Margolis, Hank A. [Université Laval

    2016-01-01

    This is the AmeriFlux version of the carbon flux data for the site CA-Qcu Quebec - Eastern Boreal, Black Spruce/Jack Pine Cutover. Site Description - The ground is gently rolling with a weak slope (<5%). In mesic areas (designated as well to moderately well drained areas, according to the Canadian System of Soil Classification (Agriculture Canada Expert Committee on Soil Survey, 1983)), the soil is a ferro-humic to humic podzol covered by an organic layer having an average depth of 26 cm (Fig. 1). In humid areas, the soil is organic (imperfectly to poorly drained) with an average organic layer of 125 cm. Mesic areas accounted for approximately 75% of the total surface area of the footprint and humid areas accounted for 25%. Full-time continuous measurements eneded in 2011. Intermittent measurements are on-going as resources permit.

  13. [Malignant narcissism and sexual homicide--exemplified by the Jack Unterweger case].

    PubMed

    Haller, R

    1999-01-01

    With the syndrome of malignant narcissism, which is characterised by narcissistic personality disorder, anti-social behaviour, sadism and a marked tendency to paranoid reactions, Kernberg (1985, 1996) describes an independent form of pathological narcissism. According to Stone (1996) this is found in many mass-murderers and serial killers. On the basis of the example of Jack Unterweger the connection between malignant narcissism and sexual offence is discussed as to psychodynamic development, personality structure and psychopathology. Unterweger, who was convicted to lifelong imprisonment in 1976 for sadistic sexual murder, became a wellknown writer in prison and was released prematurely in 1990 as the Austria case of successful rehabilitation. As stated in the sentence passed against him he killed 11 prostitutes in Europe and the USA within the next 18 months, but never pleaded guilty. Psychiatric examination revealed numerous elements of malignant narcissism and the constellation of his development and life was typical of serial offenders.

  14. 50 Years of ``Scaling'' Jack Kilby's Invention

    NASA Astrophysics Data System (ADS)

    Doering, Robert

    2008-03-01

    This year is the 50th anniversary of Jack Kilby's 1958 invention of the integrated circuit (IC), for which he won the 2000 Nobel Prize in Physics. Since that invention in a laboratory at Texas Instruments, IC components have been continuously miniaturized, which has resulted in exponential improvement trends in their performance, energy efficiency, and cost per function. These improvements have created a semiconductor industry that has grown to over 250B in annual sales. The process of reducing integrated-circuit component size and associated parameters in a coordinated fashion is traditionally called ``feature-size scaling.'' Kilby's original circuit had active (transistor) and passive (resistor, capacitor) components with dimensions of a few millimeters. Today, the minimum feature sizes on integrated circuits are less than 30 nanometers for patterned line widths and down to about one nanometer for film thicknesses. Thus, we have achieved about five orders of magnitude in linear-dimension scaling over the past fifty years, which has resulted in about ten orders of magnitude increase in the density of IC components, a representation of ``Moore's Law.'' As IC features are approaching atomic dimensions, increasing emphasis is now being given to the parallel effort of further diversifying the types of components in integrated circuits. This is called ``functional scaling'' and ``more then Moore.'' Of course, the enablers for both types of scaling have been developed at many laboratories around the world. This talk will review a few of the highlights in scaling and its applications from R&D projects at Texas Instruments.

  15. Hippo, TGF-β, and Src-MAPK pathways regulate transcription of the upd3 cytokine in Drosophila enterocytes upon bacterial infection.

    PubMed

    Houtz, Philip; Bonfini, Alessandro; Liu, Xi; Revah, Jonathan; Guillou, Aurélien; Poidevin, Mickael; Hens, Korneel; Huang, Hsin-Yi; Deplancke, Bart; Tsai, Yu-Chen; Buchon, Nicolas

    2017-11-01

    Cytokine signaling is responsible for coordinating conserved epithelial regeneration and immune responses in the digestive tract. In the Drosophila midgut, Upd3 is a major cytokine, which is induced in enterocytes (EC) and enteroblasts (EB) upon oral infection, and initiates intestinal stem cell (ISC) dependent tissue repair. To date, the genetic network directing upd3 transcription remains largely uncharacterized. Here, we have identified the key infection-responsive enhancers of the upd3 gene and show that distinct enhancers respond to various stresses. Furthermore, through functional genetic screening, bioinformatic analyses and yeast one-hybrid screening, we determined that the transcription factors Scalloped (Sd), Mothers against dpp (Mad), and D-Fos are principal regulators of upd3 expression. Our study demonstrates that upd3 transcription in the gut is regulated by the activation of multiple pathways, including the Hippo, TGF-β/Dpp, and Src, as well as p38-dependent MAPK pathways. Thus, these essential pathways, which are known to control ISC proliferation cell-autonomously, are also activated in ECs to promote tissue turnover the regulation of upd3 transcription.

  16. Scaling the Drosophila Wing: TOR-Dependent Target Gene Access by the Hippo Pathway Transducer Yorkie

    PubMed Central

    Parker, Joseph; Struhl, Gary

    2015-01-01

    Organ growth is controlled by patterning signals that operate locally (e.g., Wingless/Ints [Wnts], Bone Morphogenetic Proteins [BMPs], and Hedgehogs [Hhs]) and scaled by nutrient-dependent signals that act systemically (e.g., Insulin-like peptides [ILPs] transduced by the Target of Rapamycin [TOR] pathway). How cells integrate these distinct inputs to generate organs of the appropriate size and shape is largely unknown. The transcriptional coactivator Yorkie (Yki, a YES-Associated Protein, or YAP) acts downstream of patterning morphogens and other tissue-intrinsic signals to promote organ growth. Yki activity is regulated primarily by the Warts/Hippo (Wts/Hpo) tumour suppressor pathway, which impedes nuclear access of Yki by a cytoplasmic tethering mechanism. Here, we show that the TOR pathway regulates Yki by a separate and novel mechanism in the Drosophila wing. Instead of controlling Yki nuclear access, TOR signaling governs Yki action after it reaches the nucleus by allowing it to gain access to its target genes. When TOR activity is inhibited, Yki accumulates in the nucleus but is sequestered from its normal growth-promoting target genes—a phenomenon we term “nuclear seclusion.” Hence, we posit that in addition to its well-known role in stimulating cellular metabolism in response to nutrients, TOR also promotes wing growth by liberating Yki from nuclear seclusion, a parallel pathway that we propose contributes to the scaling of wing size with nutrient availability. PMID:26474042

  17. Derivation of jack movement influence coefficients as a basis for selecting wall contours giving reduced levels of interference in flexible walled test sections

    NASA Technical Reports Server (NTRS)

    Goodyer, M. J.

    1985-01-01

    This report covers work done in a transonic wind tunnel towards providing data on the influence of the movement of wall-control jacks on the Mach number perturbations along the test section. The data is derived using an existing streamline-curvature program, and in application is reduced to matrices of influence coefficients.

  18. Jack Rabbit Pretest Data For TATB Based IHE Model Development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hart, M M; Strand, O T; Bosson, S T

    The Jack Rabbit Pretest series consisted of 5 focused hydrodynamic experiments, 2021E PT3, PT4, PT5, PT6, and PT7. They were fired in March and April of 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory, Livermore, California. These experiments measured dead-zone formation and impulse gradients created during the detonation of TATB based insensitive high explosive. This document contains reference data tables for all 5 experiments. These data tables include: (1) Measured laser velocimetry of the experiment diagnostic plate (2) Computed diagnostic plate profile contours through velocity integration (3) Computed center axis pressures through velocity differentiation. All timesmore » are in microseconds, referenced from detonator circuit current start. All dimensions are in millimeters. Schematic axi-symmetric cross sections are shown for each experiment. These schematics detail the materials used and dimensions of the experiment and component parts. This should allow anyone wanting to evaluate their TATB based insensitive high explosive detonation model against experiment. These data are particularly relevant in examining reactive flow detonation model prediction in computational simulation of dead-zone formation and resulting impulse gradients produced by detonating TATB based explosive.« less

  19. Jack Rabbit Pretest 2021E PT3 Photonic Doppler Velocimetry Data Volume 3 Section 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hart, M M; Strand, O T; Bosson, S T

    The Jack Rabbit Pretest (PT) 2021E PT3 was fired on March 12, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT3, 120 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on the centralmore » axis and at 10, 20, 25, 30, 35, 40, 50 millimeters from the central axis. The experiment was shot at an ambient room temperature of 65 degrees Fahrenheit. The earliest PDV signal extinction was 41.7 microseconds at 30 millimeters. The latest PDV signal extinction time was 65.0 microseconds at 10 millimeters. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 40 millimeters at 10.9 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1636 meters per second. At 40 millimeters the last measured velocity was 2056 meters per second. The low-to-high velocity ratio was 0.80. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 64.6 kilobars at 15.7 microseconds. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 2.2 microseconds.« less

  20. Jack Rabbit Pretest 2021E PT4 Photonic Doppler Velocimetry Data Volume 4 Section 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hart, M M; Strand, O T; Bosson, S T

    The Jack Rabbit Pretest (PT) 2021E PT4 was fired on March 19, 2008 at the Contained Firing Facility, Site 300, Lawrence Livermore National Laboratory. This experiment is part of an effort to determine the properties of LX-17 in a regime where corner-turning behavior and dead-zone formation are not well understood. Photonic Doppler Velocimetry (PDV) measured diagnostic plate velocities confirming the presence of a persistent LX-17 dead-zone formation and the resultant impulse gradient applied under the diagnostic plate. The Jack Rabbit Pretest 2021E PT4, 120 millimeter diameter experiment returned data on all eight PDV probes. The probes measured on the centralmore » axis and at 10, 20, 25, 30, 35, 40, 50 millimeters from the central axis. The experiment was shot at an ambient room temperature of 64 degrees Fahrenheit. The earliest PDV signal extinction was 44.9 microseconds at 30 millimeters. The latest PDV signal extinction time was 69.5 microseconds at 10 millimeters. The measured velocity ranged from meters per second to thousands of meters per second. First detonation wave induced jump-off was measured at 50 millimeters at 13.3 microseconds. The PDV data provided an unambiguous indication of dead-zone formation and an impulse gradient applied to the diagnostic plate. The central axis had a last measured velocity of 1558 meters per second. At 40 millimeters the last measured velocity was 2019 meters per second. The low-to-high velocity ratio was 0.77. Velocity data was integrated to compute diagnostic plate cross section profiles. Velocity data was differentiated to compute a peak pressure under the diagnostic plate at the central axis of 98.6 kilobars at 15.0 microseconds. Substantial motion (>1 m/s) of the diagnostic plate over the dead-zone is followed by detonation region motion within approximately 0.7 microseconds.« less