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Sample records for rho gdi action

  1. RhoGDI: multiple functions in the regulation of Rho family GTPase activities

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability...... insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... of activities....

  2. An adventitious interaction of filamin A with RhoGDI2(Tyr153Glu)

    International Nuclear Information System (INIS)

    Song, Mia; He, Qianjing; Berk, Benjamin-Andreas; Hartwig, John H.; Stossel, Thomas P.; Nakamura, Fumihiko

    2016-01-01

    Filamin A (FLNA) is an actin filament crosslinking protein with multiple intracellular binding partners. Mechanical force exposes cryptic FLNA binding sites for some of these ligands. To identify new force-dependent binding interactions, we used a fusion construct composed of two FLNA domains, one of which was previously identified as containing a force-dependent binding site as a bait in a yeast two-hybrid system and identified the Rho dissociation inhibitor 2 (RhoGDI2) as a potential interacting partner. A RhoGDI2 truncate with 81 N-terminal amino acid residues and a phosphomimetic mutant, RhoGDI(Tyr153Glu) interacted with the FLNA construct. However, neither wild-type or full-length RhoGDI2 phosphorylated at Y153 interacted with FLNA. Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona–fide interaction. Therefore, previous studies reporting that a RhoGDI(Y153E) mutant suppresses the metastasis of human bladder cancer cells must be reinvestigated in light of artificial interaction of this point mutant with FLNA. - Highlights: • RhoGDI2 is identified as a potential filamin A (FLNA)-binding partner. • Phosphomimetic mutant, RhoGDI2(Tyr153Glu) interacts with FLNA. • RhoGDI2 phosphorylated (Tyr153) by src kinase does not interact with FLNA. • Mutation of Tyr-153 to Glu of RhoGDI2 does not mimic phosphorylation. • RhoGDI2(Tyr153Glu) provokes an adventitious interaction with FLNA.

  3. An adventitious interaction of filamin A with RhoGDI2(Tyr153Glu)

    Energy Technology Data Exchange (ETDEWEB)

    Song, Mia; He, Qianjing [Hematology Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston MA (United States); Berk, Benjamin-Andreas [Faculty of Veterinary Medicine and Faculty of Biosciences and Pharmacy, University of Leipzig, Leipzig (Germany); Hartwig, John H.; Stossel, Thomas P. [Hematology Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston MA (United States); Nakamura, Fumihiko, E-mail: fnakamura@partners.org [Hematology Division, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston MA (United States)

    2016-01-15

    Filamin A (FLNA) is an actin filament crosslinking protein with multiple intracellular binding partners. Mechanical force exposes cryptic FLNA binding sites for some of these ligands. To identify new force-dependent binding interactions, we used a fusion construct composed of two FLNA domains, one of which was previously identified as containing a force-dependent binding site as a bait in a yeast two-hybrid system and identified the Rho dissociation inhibitor 2 (RhoGDI2) as a potential interacting partner. A RhoGDI2 truncate with 81 N-terminal amino acid residues and a phosphomimetic mutant, RhoGDI(Tyr153Glu) interacted with the FLNA construct. However, neither wild-type or full-length RhoGDI2 phosphorylated at Y153 interacted with FLNA. Our interpretation of these contradictions is that truncation and/or mutation of RhoGDI2 perturbs its conformation to expose a site that adventitiously binds FLNA and is not a bona–fide interaction. Therefore, previous studies reporting that a RhoGDI(Y153E) mutant suppresses the metastasis of human bladder cancer cells must be reinvestigated in light of artificial interaction of this point mutant with FLNA. - Highlights: • RhoGDI2 is identified as a potential filamin A (FLNA)-binding partner. • Phosphomimetic mutant, RhoGDI2(Tyr153Glu) interacts with FLNA. • RhoGDI2 phosphorylated (Tyr153) by src kinase does not interact with FLNA. • Mutation of Tyr-153 to Glu of RhoGDI2 does not mimic phosphorylation. • RhoGDI2(Tyr153Glu) provokes an adventitious interaction with FLNA.

  4. Mechanisms of RhoGDI2 Mediated Lung Cancer Epithelial-Mesenchymal Transition Suppression

    Directory of Open Access Journals (Sweden)

    Huiyan Niu

    2014-11-01

    Full Text Available Background: The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment. Methods: The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR, western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings. Results: Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs. Conclusion: These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.

  5. NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

    Science.gov (United States)

    Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

    2017-01-01

    The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Protein Tyrosine Phosphatase-PEST and β8 Integrin Regulate Spatiotemporal Patterns of RhoGDI1 Activation in Migrating Cells

    Science.gov (United States)

    Lee, Hye Shin; Cheerathodi, Mujeeburahiman; Chaki, Sankar P.; Reyes, Steve B.; Zheng, Yanhua; Lu, Zhimin; Paidassi, Helena; DerMardirossian, Celine; Lacy-Hulbert, Adam; Rivera, Gonzalo M.

    2015-01-01

    Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor β8 integrin that plays essential roles in directional cell motility. β8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells. PMID:25666508

  7. The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI

    DEFF Research Database (Denmark)

    Scheffzek, K; Stephan, I; Jensen, Ole Nørregaard

    2000-01-01

    Rho family-specific guanine nucleotide dissociation inhibitors (RhoGDIs) decrease the rate of nucleotide dissociation and release Rho proteins such as RhoA, Rac and Cdc42 from membranes, forming tight complexes that shuttle between cytosol and membrane compartments. We have solved the crystal...

  8. Diacylglycerol kinase ζ regulates RhoA activation via a kinase-independent scaffolding mechanism

    DEFF Research Database (Denmark)

    Ard, Ryan; Mulatz, Kirk; Abramovici, Hanan

    2012-01-01

    , but the underlying mechanisms are unclear. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, selectively dissociates Rac1 by stimulating PAK1-mediated phosphorylation of RhoGDI on Ser-101/174. Similarly, phosphorylation of RhoGDI on Ser-34 by protein kinase Cα (PKCα......GDI and was required for efficient interaction of PKCα and RhoA. DGKζ-null fibroblasts had condensed F-actin bundles and altered focal adhesion distribution, indicative of aberrant RhoA signaling. Two targets of the RhoA effector ROCK showed reduced phosphorylation in DGKζ-null cells. Collectively our findings suggest...

  9. Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression.

    Science.gov (United States)

    Hooshmand, Somayeh; Ghaderi, Abbas; Yusoff, Khatijah; Thilakavathy, Karuppiah; Rosli, Rozita; Mojtahedi, Zahra

    2014-01-01

    The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα. The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

  10. Kindlin-2 Association with Rho GDP-Dissociation Inhibitor α Suppresses Rac1 Activation and Podocyte Injury.

    Science.gov (United States)

    Sun, Ying; Guo, Chen; Ma, Ping; Lai, Yumei; Yang, Fan; Cai, Jun; Cheng, Zhehao; Zhang, Kuo; Liu, Zhongzhen; Tian, Yeteng; Sheng, Yue; Tian, Ruijun; Deng, Yi; Xiao, Guozhi; Wu, Chuanyue

    2017-12-01

    Alteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure. Through proteomic analyses and in vitro coimmunoprecipitation experiments, we identified Rho GDP-dissociation inhibitor α (RhoGDI α ) as a Kindlin-2-associated protein. Loss of Kindlin-2 in podocytes significantly reduced the expression of RhoGDI α and resulted in the dissociation of Rac1 from RhoGDI α , leading to Rac1 hyperactivation and increased motility of podocytes. Inhibition of Rac1 activation effectively suppressed podocyte motility and alleviated the podocyte defects and proteinuria induced by the loss of Kindlin-2 in vivo Our results identify a novel Kindlin-2-RhoGDI α -Rac1 signaling axis that is critical for regulation of podocyte structure and function in vivo and provide evidence that it may serve as a useful target for therapeutic control of podocyte injury and associated glomerular diseases. Copyright © 2017 by the American Society of Nephrology.

  11. TrkB-T1 regulates the RhoA signaling and actin cytoskeleton in glioma cells

    International Nuclear Information System (INIS)

    Ohira, Koji; Homma, Koichi J.; Hirai, Hirohisa; Nakamura, Shun; Hayashi, Motoharu

    2006-01-01

    Recently, the truncated TrkB receptor, T1, has been reported to be involved in the control of cell morphology via the regulation of Rho proteins, through which T1 binds Rho guanine nucleotide dissociation inhibitor (Rho GDI) 1 and dissociates it in a brain-derived neurotrophic factor (BDNF)-dependent manner. However, it is unclear whether T1 signaling regulates the downstream of Rho signaling and the actin cytoskeleton. In this study, we investigated this question using C6 rat glioma cells, which express T1 endogenously. Rho GDI1 was dissociated from T1 in a BDNF-dependent manner, which also causes decreases in the activities of Rho-signaling molecules such as RhoA, Rho-associated kinase, p21-activated kinase, and extracellular-signal regulated kinase1/2. Moreover, BDNF treatment resulted in the disappearance of stress fibers in the cells treated with lysophosphatidic acid, an activator of RhoA, and in morphological changes in cells. Furthermore, a competitive assay with cyan fluorescent protein fusion proteins of T1-specific sequences reduced the effects of BDNF. These results suggest that T1 regulates the Rho-signaling pathways and the actin cytoskeleton

  12. Yersinia Virulence Depends on Mimicry of Host Rho-Family Nucleotide Dissociation Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Prehna,G.; Ivanov, M.; Blisha, J.; Stebbins, C.

    2006-01-01

    Yersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal disruption. In cell culture experiments, the kinase and the GDI domains of YpkA act synergistically to promote cytoskeletal disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in a mouse infection assay. We conclude that virulence in Yersinia depends strongly upon mimicry of host GDI proteins by YpkA.

  13. Situation of Mitsubishi's GDI engine; Etat des lieux sur le moteur GDI de Mitsubishi

    Energy Technology Data Exchange (ETDEWEB)

    Perran, Th

    1999-11-01

    Mitsubishi company (Japan) has developed an internal combustion engine which combines the qualities of both conventional spark ignition and diesel engines. This engine can work in two radically different ways depending on the regime. The GDI engine can save 40% of fuel at low regime and shows a 10% increase of torque with respect to conventional engines thanks to a better freedom in the preparation of the air/fuel mixture inside the cylinder. Moreover, using exhaust gas recirculation systems and NOx reduction catalysts, a reduction of the CO{sub 2} and NOx emissions of 20% and 90%, respectively, can be reached. On September 28, 1998, Mitsubishi presented its Pistachio model equipped with the GDI-ASG engine, one of the last evolutions of the GDI technology. This model can cover 30 km with only 1 l of petrol, i.e. 2 km more than Toyota's Prius hybrid car, and is two times less expensive. (J.S.)

  14. Common Rail System for GDI Engines Modelling, Identification, and Control

    CERN Document Server

    Fiengo, Giovanni; Palladino, Angelo; Giglio, Veniero

    2013-01-01

    Progressive reductions in vehicle emission requirements have forced the automotive industry to invest in research and development of alternative control strategies. Continual control action exerted by a dedicated electronic control unit ensures that best performance in terms of pollutant emissions and power density is married with driveability and diagnostics. Gasoline direct injection (GDI) engine technology is a way to attain these goals. This brief describes the functioning of a GDI engine equipped with a common rail (CR) system, and the devices necessary to run test-bench experiments in detail. The text should prove instructive to researchers in engine control and students are recommended to this brief as their first approach to this technology. Later chapters of the brief relate an innovative strategy designed to assist with the engine management system; injection pressure regulation for fuel pressure stabilization in the CR fuel line is proposed and validated by experiment. The resulting control scheme ...

  15. LyGDI expression in HeLa cells increased its sensitivity to radiation-induced apoptosis

    International Nuclear Information System (INIS)

    Zhou Xinwen; Xu Yaxiang

    2006-01-01

    Objective: In order to confirm whether LyGDI has apoptotic signal transduction function and can increase the apoptotic rate of radiation-induced cell death, the lyGDI and mutant D19lyGDI gene, which constructed with the pCDNA3. 1 His A, were transfected into no-endogenous lyGDI HeLa cells. Methods Transient expressions of lyGDI and D19lyGDI in HeLa cells were analyzed by Western blot using anti-mono antibody of LyGDI and Xpress tag. Cell apoptosis was assayed with Annexin V-FITC apoptosis kit. To select stable clone, the transferred HeLa cells had been maintained in G418 medium for 3 weeks, then a cell line, which stably expressed LyGDI and mutant D19lyGDI, was selected. The selected cell line was irradiated with 12 Gy 60 Co y-rays. Caspase-3 activity of the cells was determined by Western blot and cell viability by clone-forming assay after 48 hours post-irradiation culture. Results: Western blot and Annexin V-FITC apoptotic analysis revealed that lyGDI and D19lyGDI transient expressions in HeLa cells induced apoptosis; Caspase-3 activity measurement and clone-forming assay showed that lyGDI increased sensitivity to radiation-induced cell apoptosis. Conclusions: lyGDI performs function in apoptosis signal transduction, its expression in HeLa cells can increase the sensitivity to radiation-induced cell apoptosis. (authors)

  16. Recognition and stabilization of geranylgeranylated human Rab5 by the GDP Dissociation Inhibitor (GDI).

    Science.gov (United States)

    Edler, Eileen; Stein, Matthias

    2017-10-25

    The small GTPase Rab5 is the key regulator of early endosomal fusion. It is post-translationally modified by covalent attachment of two geranylgeranyl (GG) chains to adjacent cysteine residues of the C-terminal hypervariable region (HVR). The GDP dissociation inhibitor (GDI) recognizes membrane-associated Rab5(GDP) and serves to release it into the cytoplasm where it is kept in a soluble state. A detailed new structural and dynamic model for human Rab5(GDP) recognition and binding with human GDI at the early endosome membrane and in its dissociated state is presented. In the cytoplasm, the GDI protein accommodates the GG chains in a transient hydrophobic binding pocket. In solution, two different binding modes of the isoprenoid chains inserted into the hydrophobic pocket of the Rab5(GDP):GDI complex can be identified. This equilibrium between the two states helps to stabilize the protein-protein complex in solution. Interprotein contacts between the Rab5 switch regions and characteristic patches of GDI residues from the Rab binding platform (RBP) and the C-terminus coordinating region (CCR) reveal insight on the formation of such a stable complex. GDI binding to membrane-anchored Rab5(GDP) is initially mediated by the solvent accessible switch regions of the Rab-specific RBP. Formation of the membrane-associated Rab5(GDP):GDI complex induces a GDI reorientation to establish additional interactions with the Rab5 HVR. These results allow to devise a detailed structural model for the process of extraction of GG-Rab5(GDP) by GDI from the membrane and the dissociation from targeting factors and effector proteins prior to GDI binding.

  17. Light Metal Decorated Graphdiyne (GDY) Nanosheets for Reversible Hydrogen Storage.

    Science.gov (United States)

    Panigrahi, P; Dhinakaran, A K; Naqvi, S R; Rao, Sankara Gollu; Ahuja, Rajeev; Hussain, Tanveer

    2018-05-29

    The sensitive nature of molecular hydrogen (H2) interaction with the surfaces of pristine and functionalized nanostructures, especially two-dimensional materials (2D) has been a subject of debate for a while now. An accurate approximation of H2 adsorption mechanism has a vital significance for the specific fields like H2 storage applications. Owing to the importance of this issue, we have performed a comprehensive DFT study by means of several different approximations to investigate the structural, electronic, charge transfer and energy storage properties of pristine and functionalized graphdiyne (GDY) nano sheets. The dopants considered here include light-metals Li, Na, K, Ca, Sc and Ti, which make uniform distribution over GDY even at high doping concentration due to their strong binding and charge transfer mechanism. Upon 11% of metal functionalization, GDY changes into metallic state from being a small band gap semiconductor. Such situations turn the dopants to a partial positive state, which is favorable for adsorption of H2 molecules. The adsorption mechanism of H2 on GDY has been studied and compared by different methods like GGA, vdW-DF and DFT-D3 functionals. It has been established that each functionalized systems anchor multiple H2 molecules with adsorption energies that falls into a suitable range regardless of the functional used for approximations. A significantly high H2 storage capacity would guarantee that light metal-doped GDY nano sheets could serve the purpose of an efficient and reversible H2 storage material. © 2018 IOP Publishing Ltd.

  18. Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at cortico-lateral amygdala synaptic connections.

    Directory of Open Access Journals (Sweden)

    Veronica Bianchi

    Full Text Available The GDI1 gene encodes αGDI, which retrieves inactive GDP-bound RAB from membranes to form a cytosolic pool awaiting vesicular release. Mutations in GDI1 are responsible for X-linked Intellectual Disability. Characterization of the Gdi1-null mice has revealed alterations in the total number and distribution of hippocampal and cortical synaptic vesicles, hippocampal short-term synaptic plasticity and specific short-term memory deficits in adult mice, which are possibly caused by alterations of different synaptic vesicle recycling pathways controlled by several RAB GTPases. However, interpretation of these studies is complicated by the complete ablation of Gdi1 in all cells in the brain throughout development. In this study, we generated conditionally gene-targeted mice in which the knockout of Gdi1 is restricted to the forebrain, hippocampus, cortex and amygdala and occurs only during postnatal development. Adult mutant mice reproduce the short-term memory deficit previously reported in Gdi1-null mice. Surprisingly, the delayed ablation of Gdi1 worsens the pre-synaptic phenotype at cortico-amygdala synaptic connections compared to Gdi1-null mice. These results suggest a pivotal role of αGDI via specific RAB GTPases acting specifically in forebrain regions at the pre-synaptic sites involved in memory formation.

  19. Comparisons of the nanoparticle emission characteristics between GDI and PFI vehicles

    Science.gov (United States)

    Jang, Jihwan; Lee, Jongtae; Kim, Jeongsoo; Park, Sungwook

    2015-12-01

    To compare the particle emissions of gasoline direct injection (GDI) and port fuel injection (PFI) vehicles in this study, the particulate matter of exhaust emissions was sampled from a constant volume sampler tunnel and tailpipe using a chassis dynamometer. Using the gravimetric method and a condensation particle counter, the particulate matter mass (PM) and particle number (PN) of the particle size according to the current regulations were measured. Nanometer-sized particle emissions, which are smaller than regulated particle emissions, were measured by an engine exhaust particle sizer. Four test vehicles, which included two GDI vehicles and two PFI vehicles, were tested in various driving modes. The test results show that the particle emissions from the GDI vehicles were higher than the particle emissions from the PFI vehicles. In addition, the test vehicles had the highest emissions in cold start conditions. In the GDI vehicles, the PM and PN satisfied the current regulations but PN did not satisfy the EURO 6c regulations that will be implemented in 2017. In all driving modes, the particle size distribution show that the most common particle size was approximately 50 nm, and the results according to the driving patterns of each mode were confirmed.

  20. Comparisons of the nanoparticle emission characteristics between GDI and PFI vehicles

    International Nuclear Information System (INIS)

    Jang, Jihwan; Lee, Jongtae; Kim, Jeongsoo; Park, Sungwook

    2015-01-01

    To compare the particle emissions of gasoline direct injection (GDI) and port fuel injection (PFI) vehicles in this study, the particulate matter of exhaust emissions was sampled from a constant volume sampler tunnel and tailpipe using a chassis dynamometer. Using the gravimetric method and a condensation particle counter, the particulate matter mass (PM) and particle number (PN) of the particle size according to the current regulations were measured. Nanometer-sized particle emissions, which are smaller than regulated particle emissions, were measured by an engine exhaust particle sizer. Four test vehicles, which included two GDI vehicles and two PFI vehicles, were tested in various driving modes. The test results show that the particle emissions from the GDI vehicles were higher than the particle emissions from the PFI vehicles. In addition, the test vehicles had the highest emissions in cold start conditions. In the GDI vehicles, the PM and PN satisfied the current regulations but PN did not satisfy the EURO 6c regulations that will be implemented in 2017. In all driving modes, the particle size distribution show that the most common particle size was approximately 50 nm, and the results according to the driving patterns of each mode were confirmed

  1. Comparisons of the nanoparticle emission characteristics between GDI and PFI vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jihwan [Graduate School of Hanyang University (Korea, Republic of); Lee, Jongtae; Kim, Jeongsoo [National Institute of Environmental Research (Korea, Republic of); Park, Sungwook, E-mail: parks@hanyang.ac.kr [Hanyang University, School of Mechanical Engineering (Korea, Republic of)

    2015-12-15

    To compare the particle emissions of gasoline direct injection (GDI) and port fuel injection (PFI) vehicles in this study, the particulate matter of exhaust emissions was sampled from a constant volume sampler tunnel and tailpipe using a chassis dynamometer. Using the gravimetric method and a condensation particle counter, the particulate matter mass (PM) and particle number (PN) of the particle size according to the current regulations were measured. Nanometer-sized particle emissions, which are smaller than regulated particle emissions, were measured by an engine exhaust particle sizer. Four test vehicles, which included two GDI vehicles and two PFI vehicles, were tested in various driving modes. The test results show that the particle emissions from the GDI vehicles were higher than the particle emissions from the PFI vehicles. In addition, the test vehicles had the highest emissions in cold start conditions. In the GDI vehicles, the PM and PN satisfied the current regulations but PN did not satisfy the EURO 6c regulations that will be implemented in 2017. In all driving modes, the particle size distribution show that the most common particle size was approximately 50 nm, and the results according to the driving patterns of each mode were confirmed.

  2. Modelling noise propagation using Grid Resources. Progress within GDI-Grid

    Science.gov (United States)

    Kiehle, Christian; Mayer, Christian; Padberg, Alexander; Stapelfeld, Hartmut

    2010-05-01

    Modelling noise propagation using Grid Resources. Progress within GDI-Grid. GDI-Grid (english: SDI-Grid) is a research project funded by the German Ministry for Science and Education (BMBF). It aims at bridging the gaps between OGC Web Services (OWS) and Grid infrastructures and identifying the potential of utilizing the superior storage capacities and computational power of grid infrastructures for geospatial applications while keeping the well-known service interfaces specified by the OGC. The project considers all major OGC webservice interfaces for Web Mapping (WMS), Feature access (Web Feature Service), Coverage access (Web Coverage Service) and processing (Web Processing Service). The major challenge within GDI-Grid is the harmonization of diverging standards as defined by standardization bodies for Grid computing and spatial information exchange. The project started in 2007 and will continue until June 2010. The concept for the gridification of OWS developed by lat/lon GmbH and the Department of Geography of the University of Bonn is applied to three real-world scenarios in order to check its practicability: a flood simulation, a scenario for emergency routing and a noise propagation simulation. The latter scenario is addressed by the Stapelfeldt Ingenieurgesellschaft mbH located in Dortmund adapting their LimA software to utilize grid resources. Noise mapping of e.g. traffic noise in urban agglomerates and along major trunk roads is a reoccurring demand of the EU Noise Directive. Input data requires road net and traffic, terrain, buildings and noise protection screens as well as population distribution. Noise impact levels are generally calculated in 10 m grid and along relevant building facades. For each receiver position sources within a typical range of 2000 m are split down into small segments, depending on local geometry. For each of the segments propagation analysis includes diffraction effects caused by all obstacles on the path of sound propagation

  3. RhoA/Rho-Kinase in the Cardiovascular System.

    Science.gov (United States)

    Shimokawa, Hiroaki; Sunamura, Shinichiro; Satoh, Kimio

    2016-01-22

    Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase-dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system. © 2016 American Heart Association, Inc.

  4. Light-Duty GDI Vehicle PM and VOC Speciated Emissions at Differing Ambient Temperatures with Ethanol Blend Gasoline

    Science.gov (United States)

    With the rise in the use of ethanol-blend gasoline in the US and more manufacturers implementing gasoline direct injection (GDI) technologies, interest is increasing in how these fuel blends affect PM and VOC emissions in GDI technology vehicles. EPA conducted a study characteri...

  5. Delayed K562 cell apoptosis promoted by cleaved LyGDI after 60Co γ-rays irradiation

    International Nuclear Information System (INIS)

    Sun Huali; Duan Weiming; Shao Yanyan; Xiao Hainan; Zhou Xinwen

    2010-01-01

    Objective: To elucidate the function and regulatory mechanism of LyGDI involved delayed cell death in the human K562 cells and HL-60 cells induced by 60 Co γ-rays. Methods: Erythrosine B cells staining was used to count the apoptosis rate. PI staining and flow cytometry were applied to check the cell cycle. The expression of LYGDI and Rac1 was resolved by Western blot by using monoclonal antibody of LyGDI and Rac1. The distribution of Rac1 protein in cells was observed with immunofluorescence by using the confocal microscope. Results: The K562 cells showed G 2 /M phase arrest and the percent age was 71.3%. The apoptosis rate was very low at early post-irradiation stage in the K562 cells. The apoptosis rate was 14% in the K562 cells at 24 h post-irradiation with 8 Gy of γ-rays, and delayed cell apoptosis was present. LyGDI was cleaved in the K562 cells irradiated by 4 Gy 60 Co γ-rays after 24 hours post-irradiation. The expression of Rac1 protein was not altered at all, but the distribution was changed in the irradiated cells while the Rac1 protein moved to cell membrane and a little in cell nucleus. The Rac1 was activated with the losing the binding affinity with the LyGDI. Conclusion: LyGDI could promote the delayed cell apoptosis, which is through the activation of the Rac1. (authors)

  6. Mechanism of RhoB/FTI Action in Breast Cancer

    National Research Council Canada - National Science Library

    Kamasani, Uma R; Prendergast, George

    2004-01-01

    .... What factors dictate FTI efficacy? In this period, we advanced our studies of the role of cyclin B1, a key regulator of mitosis, as a critical target for RhoB suppression in FTI-induced apoptosis...

  7. Mechanism of RhoB/FTI Action in Breast Cancer

    National Research Council Canada - National Science Library

    Kamasani, Uma

    2003-01-01

    .... What factors dictate FTI efficacy? Work completed earlier in this project defined rules for RhoB and its downstream effector kinase PRK in mediating growth inhibition by FTI in epithelial cells, including human breast epithelial cells...

  8. GDI based full adders for energy efficient arithmetic applications

    Directory of Open Access Journals (Sweden)

    Mohan Shoba

    2016-03-01

    Full Text Available Addition is a vital arithmetic operation and acts as a building block for synthesizing all other operations. A high-performance adder is one of the key components in the design of application specific integrated circuits. In this paper, three low power full adders are designed with full swing AND, OR and XOR gates to alleviate threshold voltage problem which is commonly encountered in Gate Diffusion Input (GDI logic. This problem usually does not allow the full adder circuits to operate without additional inverters. However, the three full adders are successfully realized using full swing gates with the significant improvement in their performance. The performance of the proposed designs is compared with the other full adder designs, namely CMOS, CPL, hybrid and GDI through SPICE simulations using 45 nm technology models. Simulation results reveal that proposed designs have lower energy consumption among all the conventional designs taken for comparison.

  9. Mouse macrophages completely lacking Rho (RhoA, RhoB and RhoC) have severe lamellipodial retraction defects, but robust chemotactic navigation and increased motility

    DEFF Research Database (Denmark)

    Koenigs, Volker; Jennings, Richard; Vogl, Thomas

    2014-01-01

    RhoA is thought to be essential for coordination of the membrane protrusions and retractions required for immune cell motility and directed migration. Whether the subfamily of Rho (Ras homolog) GTPases (RhoA, RhoB and RhoC) is actually required for the directed migration of primary cells is diffi...

  10. High energy photoproduction of the rho and rho' vector mesons

    International Nuclear Information System (INIS)

    Bronstein, J.M.

    1977-01-01

    In an experiment in the broad band photon beam at Fermilab diffractive production of 2π + and 4π +- states from Be, Al, Cu, and Pb targets was observed. The 2π + data are dominated by the rho(770) and the 4π +- is dominated by the rho'(1500). The energy dependence of rho photoproduction from Be was measured, and no evidence was seen for energy variation of the forward cross section in the range 30 to 160 GeV. The forward cross section is consistent with its average value d sigma/dtlt. slash 0 = 3.42 +- 0.28 μb/GeV 2 over the entire range. For the /sub rho'// a mass of 1487 +- 20 MeV and a width of 675 +- 60 MeV are obtained. All quoted errors are statistical. A standard optical model analysis of the A dependence of the rho and rho'/ photoproduction yields the following results. f/sub rho'/ 2 /f/sub rho/ 2 = 3.7 +- 0.7, sigma /sub rho'//sigma /sub rho/ = 1.05 +- 0.18. Results for the photon coupling constants are in good agreement with GVMD and with the e + e - storage ring results. The approximate equality of the rho-nucleon and rho'-nucleon total cross sections is inconsistent with the diagonal version of GVMD and provides strong motivation for including transitions between different vector mesons in GVMD

  11. Measurement of exclusive $\\rho^{+}\\rho^{-}$ production in mid-virtuality two-photon interactions and study of the $\\gamma \\gamma^{*} \\to \\rho\\rho$ process at LEP

    CERN Document Server

    Achard, P.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Anderhub, H.; Andreev, Valery P.; Anselmo, F.; Arefiev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, G.; Baksay, L.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bottai, S.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.; Casaus, J.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Chamizo, M.; Chang, Y.H.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; de la Cruz, B.; Cucciarelli, S.; de Asmundis, R.; Deglon, P.; Debreczeni, J.; Degre, A.; Dehmelt, K.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; Dionisi, C.; Dittmar, M.; Doria, A.; Dova, M.T.; Duchesneau, D.; Duda, M.; Echenard, B.; Eline, A.; El Hage, A.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Extermann, P.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisher, W.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gentile, S.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hirschfelder, J.; Hofer, H.; Hohlmann, M.; Holzner, G.; Hou, S.R.; Jin, B.N.; Jindal, P.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, J.K.; Kirkby, Jasper; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Le Goff, J.M.; Leiste, R.; Levtchenko, M.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Luci, C.; Luminari, L.; Lustermann, W.; Ma, W.G.; Malgeri, L.; Malinin, A.; Mana, C.; Mans, J.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Nagy, S.; Natale, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Nisati, A.; Novak, T.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Pal, I.; Palomares, C.; Paolucci, P.; Paramatti, R.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Piccolo, D.; Pierella, F.; Pioppi, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Pothier, J.; Prokofiev, D.; Rahal-Callot, G.; Rahaman, Mohammad Azizur; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Roe, B.P.; Romero, L.; Rosca, A.; Rosemann, C.; Rosenbleck, C.; Rosier-Lees, S.; Roth, Stefan; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Sakharov, A.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Schafer, C.; Schegelsky, V.; Schopper, H.; Schotanus, D.J.; Sciacca, C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Son, D.; Souga, C.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Tang, X.W.; Tarjan, P.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Ulbricht, J.; Valente, E.; Van de Walle, R.T.; Vasquez, R.; Veszpremi, V.; Vesztergombi, G.; Vetlitsky, I.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobiev, I.; Vorobyov, A.A.; Wadhwa, M.; Wang, Q.; Wang, X.L.; Wang, Z.M.; Weber, M.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Yeh, S.C.; Zalite, An.; Zalite, Yu.; Zhang, Z.P.; Zhao, J.; Zhu, G.Y.; Zhu, R.Y.; Zhuang, H.L.; Zichichi, A.; Zimmermann, B.; Zoller, M.

    2005-01-01

    Exclusive rho+rho- production in two-photon collisions between a quasi-real photon, gamma, and a mid-virtuality photon, gamma*, is studied with data collected at LEP at centre-of-mass energies root(s)=183-209GeV with a total integrated luminosity of 684.8pb^-1. The cross section of the gamma gamma* -> rho+ rho- process is determined as a function of the photon virtuality, Q^2, and the two-photon centre-of-mass energy, W_gg, in the kinematic region: 0.2GeV^2 rho rho process over the Q^2-region 0.2GeV^2 < Q^2 < 30 GeV^2.

  12. RhoA/Rho Kinase Mediates Neuronal Death Through Regulating cPLA2 Activation.

    Science.gov (United States)

    Wu, Xiangbing; Walker, Chandler L; Lu, Qingbo; Wu, Wei; Eddelman, Daniel B; Parish, Jonathan M; Xu, Xiao-Ming

    2017-11-01

    Activation of RhoA/Rho kinase leads to growth cone collapse and neurite retraction. Although RhoA/Rho kinase inhibition has been shown to improve axon regeneration, remyelination and functional recovery, its role in neuronal cell death remains unclear. To determine whether RhoA/Rho kinase played a role in neuronal death after injury, we investigated the relationship between RhoA/Rho kinase and cytosolic phospholipase A 2 (cPLA 2 ), a lipase that mediates inflammation and cell death, using an in vitro neuronal death model and an in vivo contusive spinal cord injury model performed at the 10th thoracic (T10) vertebral level. We found that co-administration of TNF-α and glutamate induced spinal neuron death, and activation of RhoA, Rho kinase and cPLA 2 . Inhibition of RhoA, Rho kinase and cPLA 2 significantly reduced TNF-α/glutamate-induced cell death by 33, 52 and 43 %, respectively (p < 0.001). Inhibition of RhoA and Rho kinase also significantly downregulated cPLA 2 activation by 66 and 60 %, respectively (p < 0.01). Furthermore, inhibition of RhoA and Rho kinase reduced the release of arachidonic acid, a downstream substrate of cPLA 2 . The immunofluorescence staining showed that ROCK 1 or ROCK 2 , two isoforms of Rho kinase, was co-localized with cPLA 2 in neuronal cytoplasm. Interestingly, co-immunoprecipitation (Co-IP) assay showed that ROCK 1 or ROCK 2 bonded directly with cPLA 2 and phospho-cPLA 2 . When the Rho kinase inhibitor Y27632 was applied in mice with T10 contusion injury, it significantly decreased cPLA 2 activation and expression and reduced injury-induced apoptosis at and close to the lesion site. Taken together, our results reveal a novel mechanism of RhoA/Rho kinase-mediated neuronal death through regulating cPLA 2 activation.

  13. oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading.

    Science.gov (United States)

    Zhang, Chongxu; Adamos, Crystal; Oh, Myung-Jin; Baruah, Jugajyoti; Ayee, Manuela A A; Mehta, Dolly; Wary, Kishore K; Levitan, Irena

    2017-09-01

    Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu 2+ -oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu 2+ -oxLDL enhanced HAECs' proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu 2+ -oxLDL and LPO-oxLDL enhance HAEC proliferation via activation of Rho, Akt phosphorylation, and a decrease in the expression of cyclin-dependent kinase inhibitor 1B (p27 kip1 ). Both Cu 2+ -oxLDL or LPO-oxLDL significantly increased Akt phosphorylation, whereas an Akt inhibitor, MK2206, blocked oxLDL-induced increase in HAEC proliferation. Blocking Rho with C3 or its downstream target ROCK with Y27632 significantly inhibited oxLDL-induced Akt phosphorylation and proliferation mediated by both Cu 2+ - and LPO-oxLDL. Activation of RhoA was blocked by Rho-GDI-1, which also abrogated oxLDL-induced Akt phosphorylation and HAEC proliferation. In contrast, blocking Rac1 in these cells had no effect on oxLDL-induced Akt phosphorylation or cell proliferation. Moreover, oxLDL-induced Rho/Akt signaling downregulated cell cycle inhibitor p27 kip1 Preloading these cells with cholesterol, however, prevented oxLDL-induced Akt phosphorylation and HAEC proliferation. These findings provide a new understanding of the effects of oxLDL on endothelial proliferation, which is essential for developing new treatments against neovascularization and progression of atherosclerosis. Copyright © 2017 the American Physiological Society.

  14. Differential binding of RhoA, RhoB, and RhoC to protein kinase C-related kinase (PRK) isoforms PRK1, PRK2, and PRK3: PRKs have the highest affinity for RhoB.

    Science.gov (United States)

    Hutchinson, Catherine L; Lowe, Peter N; McLaughlin, Stephen H; Mott, Helen R; Owen, Darerca

    2013-11-12

    Protein kinase C-related kinases (PRKs) are members of the protein kinase C superfamily of serine-threonine kinases and can be activated by binding to members of the Rho family of GTPases via a Rho-binding motif known as an HR1 domain. Three tandem HR1 domains reside at the N-terminus of the PRKs. We have assessed the ability of the HR1a and HR1b domains from the three PRK isoforms (PRK1, PRK2, and PRK3) to interact with the three Rho isoforms (RhoA, RhoB, and RhoC). The affinities of RhoA and RhoC for a construct encompassing both PRK1 HR1 domains were similar to those for the HR1a domain alone, suggesting that these interactions are mediated solely by the HR1a domain. The affinities of RhoB for both the PRK1 HR1a domain and the HR1ab didomain were higher than those of RhoA or RhoC. RhoB also bound more tightly to the didomain than to the HR1a domain alone, implicating the HR1b domain in the interaction. As compared with PRK1 HR1 domains, PRK2 and PRK3 domains bind less well to all Rho isoforms. Uniquely, however, the PRK3 domains display a specificity for RhoB that requires both the C-terminus of RhoB and the PRK3 HR1b domain. The thermal stability of the HR1a and HR1b domains was also investigated. The PRK2 HR1a domain was found to be the most thermally stable, while PRK2 HR1b, PRK3 HR1a, and PRK3 HR1b domains all exhibited lower melting temperatures, similar to that of the PRK1 HR1a domain. The lower thermal stability of the PRK2 and PRK3 HR1b domains may impart greater flexibility, driving their ability to interact with Rho isoforms.

  15. The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV Infected Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Melpomeni Tseliou

    2016-01-01

    Full Text Available Background/Aims: Rho GTPases are crucial regulators of the actin cytoskeleton, membrane trafficking and cell signaling and their importance in cell migration and invasion is well- established. The human cytomegalovirus (HCMV is a widespread pathogen responsible for generally asymptomatic and persistent infections in healthy people. Recent evidence indicates that HCMV gene products are expressed in over 90% of malignant type glioblastomas (GBM. In addition, the HCMV Immediate Early-1 protein (IE1 is expressed in >90% of tumors analyzed. Methods: RhoA, RhoB and RhoC were individually depleted in U373MG glioblastoma cells as well as U373MG cells stably expressing the HCMV IE1 protein (named U373MG-IE1 cells shRNA lentivirus vectors. Cell proliferation assays, migration as well as wound-healing assays were performed in uninfected and HCMV-infected cells. Results: The depletion of RhoA, RhoB and RhoC protein resulted in significant alterations in the morphology of the uninfected cells, which were further enhanced by the cytopathic effect caused by HCMV. Furthermore, in the absence or presence of HCMV, the knockdown of RhoB and RhoC proteins decreased the proliferation rate of the parental and the IE1-expressing glioblastoma cells, whereas the knockdown of RhoA protein in the HCMV infected cell lines restored their proliferation rate. In addition, wound healing assays in U373MG cells revealed that depletion of RhoA, RhoB and RhoC differentially reduced their migration rate, even in the presence or the absence of HCMV. Conclusion: Collectively, these data show for the first time a differential implication of Rho GTPases in morphology, proliferation rate and motility of human glioblastoma cells during HCMV infection, further supporting an oncomodulatory role of HCMV depending on the Rho isoforms' state.

  16. Revisiting UNDP’s GDI and GEM: Towards an alternative

    OpenAIRE

    Dijkstra, Geske

    2002-01-01

    textabstractThere are two reasons why it is important to have a good measure of gender equality in countries or regions. One is that it is important in itself: countries or regions want to compare their achievements in this area with those of other countries. The second is that such a measure can be used to assess the relationship between gender equality and economic development. In 1995, UNDP has developed two composite indices of gender equality, the Gender-related Development Index (GDI) a...

  17. Rho GTPases and cancer

    DEFF Research Database (Denmark)

    Li, Hui; Peyrollier, Karine; Kilic, Gülcan

    2014-01-01

    Rho GTPases are a family of small GTPases, which play an important role in the regulation of the actin cytoskeleton. Not surprisingly, Rho GTPases are crucial for cell migration and therefore highly important for cancer cell invasion and the formation of metastases. In addition, Rho GTPases...... are involved in growth and survival of tumor cells, in the interaction of tumor cells with their environment, and they are vital for the cancer supporting functions of the tumor stroma. Recent research has significantly improved our understanding of the regulation of Rho GTPase activity, the specificity of Rho...

  18. Arhgap28 is a RhoGAP that inactivates RhoA and downregulates stress fibers.

    Directory of Open Access Journals (Sweden)

    Ching-Yan Chloé Yeung

    Full Text Available The small GTPase RhoA is a major regulator of actin reorganization during the formation of stress fibers; thus identifying molecules that regulate Rho activity is necessary for a complete understanding of the mechanisms that determine cell contractility. Here, we have identified Arhgap28 as a Rho GTPase activating protein (RhoGAP that switches RhoA to its inactive form. We generated an Arhgap28-LacZ reporter mouse that revealed gene expression in soft tissues at E12.5, pre-bone structures of the limb at E15.5, and prominent expression restricted mostly to ribs and limb long bones at E18.5 days of development. Expression of recombinant Arhgap28-V5 in human osteosarcoma SaOS-2 cells caused a reduction in the basal level of RhoA activation and disruption of actin stress fibers. Extracellular matrix assembly studies using a 3-dimensional cell culture system showed that Arhgap28 was upregulated during Rho-dependent assembly of the ECM. Taken together, these observations led to the hypothesis that an Arhgap28 knockout mouse model would show a connective tissue phenotype, perhaps affecting bone. Arhgap28-null mice were viable and appeared normal, suggesting that there could be compensation from other RhoGAPs. Indeed, we showed that expression of Arhgap6 (a closely related RhoGAP was upregulated in Arhgap28-null bone tissue. An upregulation in RhoA expression was also detected suggesting that Arhgap28 may be able to additionally regulate Rho signaling at a transcriptional level. Microarray analyses revealed that Col2a1, Col9a1, Matn3, and Comp that encode extracellular matrix proteins were downregulated in Arhgap28-null bone. Although mutations in these genes cause bone dysplasias no bone phenotype was detected in the Arhgap-28 null mice. Together, these data suggest that the regulation of Rho by RhoGAPs, including Arhgap28, during the assembly and development of mechanically strong tissues is complex and may involve multiple RhoGAPs.

  19. Image processing of vaporizing GDI sprays: a new curvature-based approach

    Science.gov (United States)

    Lazzaro, Maurizio; Ianniello, Roberto

    2018-01-01

    This article introduces an innovative method for the segmentation of Mie-scattering and schlieren images of GDI sprays. The contours of the liquid phase are obtained by segmenting the scattering images of the spray by means of optimal filtering of the image, relying on variational methods, and an original thresholding procedure based on an iterative application of Otsu’s method. The segmentation of schlieren images, to get the contours of the spray vapour phase, is obtained by exploiting the surface curvature of the image to strongly enhance the intensity texture due to the vapour density gradients. This approach allows one to unambiguously discern the whole vapour phase of the spray from the background. Additional information about the spray liquid phase can be obtained by thresholding filtered schlieren images. The potential of this method has been substantiated in the segmentation of schlieren and scattering images of a GDI spray of isooctane. The fuel, heated to 363 K, was injected into nitrogen at a density of 1.12 and 3.5 kg m-3 with temperatures of 333 K and 573 K.

  20. Measurement of Exclusive $\\rho^+ \\rho^-$ Production in High-$Q^2$ Two-Photon Collisions at LEP

    CERN Document Server

    Achard, P.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Anderhub, H.; Andreev, Valery P.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, G.; Baksay, L.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bottai, S.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.; Casaus, J.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Chamizo, M.; Chang, Y.H.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; de la Cruz, B.; Cucciarelli, S.; van Dalen, J.A.; de Asmundis, R.; Deglon, P.; Debreczeni, J.; Degre, A.; Dehmelt, K.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; Dionisi, C.; Dittmar, M.; Doria, A.; Dova, M.T.; Duchesneau, D.; Duda, M.; Echenard, B.; Eline, A.; El Hage, A.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Extermann, P.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisher, W.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gentile, S.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hirschfelder, J.; Hofer, H.; Hohlmann, M.; Holzner, G.; Hou, S.R.; Hu, Y.; Jin, B.N.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, J.K.; Kirkby, Jasper; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Le Goff, J.M.; Leiste, R.; Levtchenko, M.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Luci, C.; Luminari, L.; Lustermann, W.; Ma, W.G.; Malgeri, L.; Malinin, A.; Mana, C.; Mans, J.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Nagy, S.; Natale, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Nisati, A.; Novak, T.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Pal, I.; Palomares, C.; Paolucci, P.; Paramatti, R.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Petersen, B.; Piccolo, D.; Pierella, F.; Pioppi, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Pothier, J.; Prokofev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, Mohammad Azizur; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Roe, B.P.; Romero, L.; Rosca, A.; Rosemann, C.; Rosenbleck, C.; Rosier-Lees, S.; Roth, Stefan; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Sakharov, A.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Schafer, C.; Schegelsky, V.; Schopper, H.; Schotanus, D.J.; Sciacca, C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Son, D.; Souga, C.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Tang, X.W.; Tarjan, P.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Ulbricht, J.; Valente, E.; Van de Walle, R.T.; Vasquez, R.; Veszpremi, V.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobyov, A.A.; Wadhwa, M.; Wang, Q.; Wang, X.L.; Wang, Z.M.; Weber, M.; Wilkens, H.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Yeh, S.C.; Zalite, An.; Zalite, Yu.; Zhang, Z.P.; Zhao, J.; Zhu, G.Y.; Zhu, R.Y.; Zhuang, H.L.; Zichichi, A.; Zimmermann, B.; Zoller, M.

    2004-01-01

    Exclusive rho^+ rho^- production in two-photon collisions involving a single highly-virtual photon is studied with data collected at LEP at centre-of-mass energies 89 GeV rho^+ rho^- is determined as a function of the photon virtuality, Q^2, and the two-photon centre-of-mass energy, W_gg, in the kinematic region: 1.2 GeV^2 rho^0 rho^0, measured in the same kinematic region by L3, and to have similar W_gg and Q^2 dependences.

  1. Effects of chronic Δ9-tetrahydrocannabinol treatment on Rho/Rho-kinase signalization pathway in mouse brain

    Directory of Open Access Journals (Sweden)

    Halil Mahir Kaplan

    2017-11-01

    Full Text Available Δ9-Tetrahydrocannabinol (Δ9-THC shows its effects by activating cannabinoid receptors which are on some tissues and neurons. Cannabinoid systems have role on cell proliferation and development of neurons. Furthermore, it is interesting that cannabinoid system and rho/rho-kinase signalization pathway, which have important role on cell development and proliferation, may have role on neuron proliferation and development together. Thus, a study is planned to investigate rhoA and rho-kinase enzyme expressions and their activities in the brain of chronic Δ9-THC treated mice. One group of mice are treated with Δ9-THC once to see effects of acute treatment. Another group of mice are treated with Δ9-THC three times per day for one month. After this period, rhoA and rho-kinase enzyme expressions and their activities in mice brains are analyzed by ELISA method. Chronic administration of Δ9-THC decreased the expression of rhoA while acute treatment has no meaningful effect on it. Administration of Δ9-THC did not affect expression of rho-kinase on both chronic and acute treatment. Administration of Δ9-THC increased rho-kinase activity on both chronic and acute treatment, however, chronic treatment decreased its activity with respect to acute treatment. This study showed that chronic Δ9-THC treatment down-regulated rhoA expression and did not change the expression level of rho-kinase which is downstream effector of rhoA. However, it elevated the rho-kinase activity. Δ9-THC induced down-regulation of rhoA may cause elevation of cypin expression and may have benefit on cypin related diseases. Furthermore, use of rho-kinase inhibitors and Δ9-THC together can be useful on rho-kinase related diseases.

  2. New look at magnetism in single-crystal Gd-Y alloys

    International Nuclear Information System (INIS)

    Ito, T.; Legvold, S.; Beaudry, B.J.

    1981-01-01

    Magnetic susceptibility, electrical resistivity, and specific-heat measurements have been made on a number of polycrystalline and single-crystal samples of Gd-rich Gd-Y alloys. It has been found (i) that samples with more than 30 at. % Y exhibit a helical structure phase; (ii) that samples between 10 and 30 at. % Y exhibit two different Curie-Weiss regimes leading to ''double'' ferromagnetism; and (iii) that samples with less than 10 at. % Y have Gd-like behavior

  3. The small GTPase RhoH is an atypical regulator of haematopoietic cells

    Directory of Open Access Journals (Sweden)

    Kubatzky Katharina F

    2008-09-01

    Full Text Available Abstract Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best-characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions such as actin cytoskeleton reorganisation, adhesion, motility as well as cell proliferation, differentiation and gene transcription. Among the 20 members of that family, only Rac2 and RhoH show an expression restricted to the haematopoietic lineage. RhoH was first discovered in 1995 as a fusion transcript with the transcriptional repressor LAZ3/BCL6. It was therefore initially named translation three four (TTF but later on renamed RhoH due to its close relationship to the Ras/Rho family of GTPases. Since then, RhoH has been implicated in human cancer as the gene is subject to somatic hypermutation and by the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and acute myeloid leukaemia. Some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have been described. These include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling. Little is currently known about its signalling, regulation or interaction partners. Recent studies have shown that RhoH negatively influences the proliferation and homing of murine haematopoietic progenitor cells, presumably by acting as an antagonist for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non-adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also been

  4. Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo

    Directory of Open Access Journals (Sweden)

    Wang Haibo

    2010-09-01

    Full Text Available Abstract Background RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC in tumor-bearing nude mice in vivo. Methods To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group: (1 normal saline(NS group, (2replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK group and (3replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC group. Ad-HK (4 × 108 pfu, 30 ul/mouse, Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse or PBS (30 ul/mouse was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay was used to detect the death of cells. Results The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P RhoA and Rho

  5. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

    Directory of Open Access Journals (Sweden)

    Aniko Keller-Pinter

    Full Text Available The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs. Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu mutant of syndecan-4 (SDC4. SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1 to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

  6. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction–dependent manner

    Science.gov (United States)

    Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef

    2017-01-01

    The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1–RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways. PMID:29121646

  7. The phosphomimetic mutation of syndecan-4 binds and inhibits Tiam1 modulating Rac1 activity in PDZ interaction-dependent manner.

    Science.gov (United States)

    Keller-Pinter, Aniko; Ughy, Bettina; Domoki, Monika; Pettko-Szandtner, Aladar; Letoha, Tamas; Tovari, Jozsef; Timar, Jozsef; Szilak, Laszlo

    2017-01-01

    The small GTPases of the Rho family comprising RhoA, Rac1 and Cdc42 function as molecular switches controlling several essential biochemical pathways in eukaryotic cells. Their activity is cycling between an active GTP-bound and an inactive GDP-bound conformation. The exchange of GDP to GTP is catalyzed by guanine nucleotide exchange factors (GEFs). Here we report a novel regulatory mechanism of Rac1 activity, which is controlled by a phosphomimetic (Ser179Glu) mutant of syndecan-4 (SDC4). SDC4 is a ubiquitously expressed transmembrane, heparan sulfate proteoglycan. In this study we show that the Ser179Glu mutant binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells. Mutational analysis unravels the PDZ interaction between SDC4 and Tiam1 is indispensable for the suppression of the Rac1 activity. Neither of the SDC4 interactions is effective alone to block the Rac1 activity, on the contrary, lack of either of interactions can increase the activity of Rac1, therefore the Rac1 activity is the resultant of the inhibitory and stimulatory effects. In addition, SDC4 can bind and tether RhoGDI1 (GDP-dissociation inhibitor 1) to the membrane. Expression of the phosphomimetic SDC4 results in the accumulation of the Rac1-RhoGDI1 complex. Co-immunoprecipitation assays (co-IP-s) reveal that SDC4 can form complexes with RhoGDI1. Together, the regulation of the basal activity of Rac1 is fine tuned and SDC4 is implicated in multiple ways.

  8. Exchange mechanisms for $\\pi^{-}p\\rightarrow\\rho^{0}$n and $\\rho-\\omega$ interference

    CERN Document Server

    Estabrooks, P G; Michael, C

    1974-01-01

    The 17 GeV/c pi /sup -/p to rho /sup 0/n production amplitudes are decomposed into pi , A/sub 2/ and non-evasive exchange contributions. Independent support for this description comes from the observed rho - omega interference effects and from the energy dependence of rho /sup 0/ production data. (18 refs).

  9. Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine

    Science.gov (United States)

    Wheeler, David S.; Underhill, Suzanne M.; Stolz, Donna B.; Murdoch, Geoffrey H.; Thiels, Edda; Romero, Guillermo; Amara, Susan G.

    2015-01-01

    Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH’s effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID:26553986

  10. Cold Temperature Effects on Speciated VOC Emissions from Modern GDI Light-Duty Vehicles 1

    Science.gov (United States)

    In this study, speciated VOC emissions were characterized from three modern GDI light-duty vehicles. The vehicles were tested on a chassis dynamometer housed in a climate-controlled chamber at two temperatures (20 and 72 °F) using the EPA Federal Test Procedure (FTP) and a portio...

  11. Exome sequencing identifies a novel mutation of the GDI1 gene in a Chinese non-syndromic X-linked intellectual disability family

    Directory of Open Access Journals (Sweden)

    Yongheng Duan

    2017-08-01

    Full Text Available Abstract X-linked intellectual disability (XLID has been associated with various genes. Diagnosis of XLID, especially for non-syndromic ones (NS-XLID, is often hampered by the heterogeneity of this disease. Here we report the case of a Chinese family in which three males suffer from intellectual disability (ID. The three patients shared the same phenotype: no typical clinical manifestation other than IQ score ≤ 70. For a genetic diagnosis for this family we carried out whole exome sequencing on the proband, and validated 16 variants of interest in the genomic DNA of all the family members. A missense mutation (c.710G > T, which mapped to exon 6 of the Rab GDP-Dissociation Inhibitor 1 (GDI1 gene, was found segregating with the ID phenotype, and this mutation changes the 237th position in the guanosine diphosphate dissociation inhibitor (GDI protein from glycine to valine (p. Gly237Val. Through molecular dynamics simulations we found that this substitution results in a conformational change of GDI, possibly affecting the Rab-binding capacity of this protein. In conclusion, our study identified a novel GDI1 mutation that is possibly NS-XLID causative, and showed that whole exome sequencing provides advantages for detecting novel ID-associated variants and can greatly facilitate the genetic diagnosis of the disease.

  12. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Blom, Magdalena; Reis, Katarina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Heldin, Johan [Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala SE-751 22 Uppsala (Sweden); Kreuger, Johan [Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala (Sweden); Aspenström, Pontus, E-mail: pontus.aspenstrom@ki.se [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

    2017-03-15

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  13. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    International Nuclear Information System (INIS)

    Blom, Magdalena; Reis, Katarina; Heldin, Johan; Kreuger, Johan; Aspenström, Pontus

    2017-01-01

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  14. Experimental investigation of in-cylinder wall wetting in GDI engines using a shadowgraphy method

    NARCIS (Netherlands)

    Luijten, B.; Adomeit, P.; Brunn, A.; Somers, L.M.T.

    2013-01-01

    This paper discusses an experimental approach to compare the amount of gasoline on the liner for different engine setups. This is done in a non-fired motored gasoline direct injection (GDI) test engine with transparent liner walls. The main goal is a planar observation and detection of the liner

  15. QCD factorizations in {gamma}*{gamma}*->{rho}{sub L}{sup 0}{rho}{sub L}{sup 0}

    Energy Technology Data Exchange (ETDEWEB)

    Pire, B. [CPHT, Unite mixte 7644 du CNRS, Ecole Polytechnique, 91128 Palaiseau (France)]. E-mail: pire@cpht.polytechnique.fr; Segond, M. [LPT, Unite mixte 8627 du CNRS, Universite Paris-Sud, 91405 Orsay (France); Szymanowski, L. [LPT, Unite mixte 8627 du CNRS, Universite Paris-Sud, 91405 Orsay (France); Universite de Liege, B-4000 Liege (Belgium); Soltan Institute for Nuclear Studies, Hoza 69, 00-681 Warsaw (Poland); Wallon, S. [LPT, Unite mixte 8627 du CNRS. , Universite Paris-Sud, 91405 Orsay (France)

    2006-08-24

    We calculate the lowest order QCD amplitude, i.e. the quark exchange contribution, to the forward production amplitude of a pair of longitudinally polarized {rho} mesons in the scattering of two virtual photons {gamma}*(Q{sub 1}){gamma}*(Q{sub 2})->{rho}{sub L}{sup 0}{rho}{sub L}{sup 0}. We show that the scattering amplitude simultaneously factorizes in two quite different ways: the part with transverse photons is described by the QCD factorization formula involving the generalized distribution amplitude of two final {rho} mesons, whereas the part with longitudinally polarized photons takes the QCD factorized form with the {gamma}{sub L}*->{rho}{sub L}{sup 0} transition distribution amplitude. Perturbative expressions for these, in general, non-perturbative functions are obtained in terms of the {rho}-meson distribution amplitude.

  16. Rho GTPase expression in human myeloid cells.

    Directory of Open Access Journals (Sweden)

    Suzanne F G van Helden

    Full Text Available Myeloid cells are critical for innate immunity and the initiation of adaptive immunity. Strict regulation of the adhesive and migratory behavior is essential for proper functioning of these cells. Rho GTPases are important regulators of adhesion and migration; however, it is unknown which Rho GTPases are expressed in different myeloid cells. Here, we use a qPCR-based approach to investigate Rho GTPase expression in myeloid cells.We found that the mRNAs encoding Cdc42, RhoQ, Rac1, Rac2, RhoA and RhoC are the most abundant. In addition, RhoG, RhoB, RhoF and RhoV are expressed at low levels or only in specific cell types. More differentiated cells along the monocyte-lineage display lower levels of Cdc42 and RhoV, while RhoC mRNA is more abundant. In addition, the Rho GTPase expression profile changes during dendritic cell maturation with Rac1 being upregulated and Rac2 downregulated. Finally, GM-CSF stimulation, during macrophage and osteoclast differentiation, leads to high expression of Rac2, while M-CSF induces high levels of RhoA, showing that these cytokines induce a distinct pattern. Our data uncover cell type specific modulation of the Rho GTPase expression profile in hematopoietic stem cells and in more differentiated cells of the myeloid lineage.

  17. The atypical structure and function of newborn arterial endothelium is mediated by Rho/Rho kinase signaling.

    Science.gov (United States)

    Flavahan, Sheila; Flavahan, Nicholas A

    2014-08-15

    Endothelium of fetal or newborn arteries is atypical, displaying actin stress fibers and reduced nitric oxide (NO)-mediated dilatation. This study tested the hypothesis that Rho/Rho kinase signaling, which promotes endothelial stress fibers and inhibits endothelial dilatation, contributed to this phenotype. Carotid arteries were isolated from newborn [postnatal day 1 (P1)], P7, and P21 mice. Endothelial dilatation to acetylcholine (pressure myograph) was minimal at P1, increased at P7, and further increased at P21. Inhibition of Rho (C3 transferase) or Rho kinase (Y27632, fasudil) significantly increased dilatation to acetylcholine in P1 arteries but had no effect in P7 or P21 arteries. After inhibition of NO synthase (N(G)-nitro-l-arginine methyl ester), Rho kinase inhibition no longer increased acetylcholine responses in P1 arteries. Rho kinase inhibition did not affect dilatation to the NO donor DEA-NONOate. The endothelial actin cytoskeleton was labeled with phalloidin and visualized by laser-scanning microscopy. In P1 arteries, the endothelium had prominent transcytoplasmic stress fibers, whereas in P7 and P21 arteries, the actin fibers had a significantly reduced intensity and were restricted to cell borders. Phosphorylation of myosin light chains, a Rho kinase substrate, was highest in P1 endothelium and significantly reduced in P7 and P21 endothelium (laser-scanning microscopy). In P1 arteries, inhibition of Rho (C3 transferase) or Rho kinase (Y27632) significantly reduced the intensity of actin fibers, which were restricted to cell borders. Similarly, in P1 arteries, Rho inhibition significantly reduced endothelial levels of phosphorylated myosin light chains. These results indicate that the atypical function and morphology of newborn endothelium is mediated by Rho/Rho kinase signaling. Copyright © 2014 the American Physiological Society.

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

    Directory of Open Access Journals (Sweden)

    Kalcheim Chaya

    2008-10-01

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

  19. Rho GTPase function in tumorigenesis

    DEFF Research Database (Denmark)

    Karlsson, R; Pedersen, Esben Ditlev Kølle; Wang, Zhipeng

    2009-01-01

    , for that reason, Rho GTPases, their regulators, and their effectors have been suggested to control tumor formation and progression in humans. However, while the tumor-relevant functions of Rho GTPases are very well documented in vitro, we are only now beginning to assess their contribution to cancer in human...... patients and in animal models. This review will give a very brief overview of Rho GTPase function in general and then focus on in vivo evidence for a role of Rho GTPases in malignant tumors, both in human patients and in genetically modified mice....

  20. Rho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases

    Directory of Open Access Journals (Sweden)

    Muneo Yamaguchi

    2017-01-01

    Full Text Available Rho-associated kinase (Rho-kinase/ROCK was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs. The importance of ROCK in pathological vitreoretinal conditions has also been elucidated and is attracting attention as a potential therapeutic target. ROCK is involved in angiogenesis and hyperpermeability and also in the pathogenesis of various pathologies such as inflammation and fibrosis. It has been expected that ROCK inhibitors will become new molecular target drugs for vitreoretinal diseases. This review summarizes the recent progress on the mechanisms of action of ROCK and their applications in disease treatment.

  1. Measurement of Exclusive $\\rho^{0}\\rho^{0}$ Production in Mid-Virtuality Two-Photon Interactions at LEP

    CERN Document Server

    Achard, P.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Anderhub, H.; Andreev, Valery P.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, G.; Baksay, L.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bottai, S.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.; Casaus, J.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Chamizo, M.; Chang, Y.H.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; de la Cruz, B.; Cucciarelli, S.; de Asmundis, R.; Deglon, P.; Debreczeni, J.; Degre, A.; Dehmelt, K.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; Dionisi, C.; Dittmar, M.; Doria, A.; Dova, M.T.; Duchesneau, D.; Duda, M.; Echenard, B.; Eline, A.; El Hage, A.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Extermann, P.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisher, W.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gentile, S.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hirschfelder, J.; Hofer, H.; Hohlmann, M.; Holzner, G.; Hou, S.R.; Jin, B.N.; Jindal, P.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, J.K.; Kirkby, Jasper; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Le Goff, J.M.; Leiste, R.; Levtchenko, M.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Luci, C.; Luminari, L.; Lustermann, W.; Ma, W.G.; Malgeri, L.; Malinin, A.; Mana, C.; Mans, J.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Nagy, S.; Natale, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Nisati, A.; Novak, T.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Pal, I.; Palomares, C.; Paolucci, P.; Paramatti, R.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Piccolo, D.; Pierella, F.; Pioppi, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Pothier, J.; Prokofev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, Mohammad Azizur; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Roe, B.P.; Romero, L.; Rosca, A.; Rosemann, C.; Rosenbleck, C.; Rosier-Lees, S.; Roth, Stefan; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Sakharov, A.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Schafer, C.; Schegelsky, V.; Schopper, H.; Schotanus, D.J.; Sciacca, C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Son, D.; Souga, C.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Tang, X.W.; Tarjan, P.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Ulbricht, J.; Valente, E.; Van de Walle, R.T.; Vasquez, R.; Veszpremi, V.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobyov, A.A.; Wadhwa, M.; Wang, Q.; Wang, X.L.; Wang, Z.M.; Weber, M.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Yeh, S.C.; Zalite, An.; Zalite, Yu.; Zhang, Z.P.; Zhao, J.; Zhu, G.Y.; Zhu, R.Y.; Zhuang, H.L.; Zichichi, A.; Zimmermann, B.; Zoller, M.

    2004-01-01

    Exclusive rho^0 rho^0 production in two-photon collisions between a quasi-real and a mid-virtuality photon is studied with data collected at LEP at centre-of-mass energies 183GeV rho^0 rho^0 is determined as a function of the photon virtuality, q^2, and the two-photon centre-of-mass energy, Wgg, in the kinematic region: 0.2GeV^2 < q^2 < 0.85GeV^2 and 1.1GeV < Wgg < 3GeV.

  2. Intrinsic, pro-apoptotic effects of IGFBP-3 on breast cancer cells are reversible: Involvement of PKA, Rho and ceramide.

    Directory of Open Access Journals (Sweden)

    Claire M Perks

    2011-05-01

    Full Text Available We established previously that IGFBP-3 could exert positive or negative effects on cell function depending upon the extracellular matrix composition and by interacting with integrin signalling. To elicit its pro-apoptotic effects IGFBP-3 bound to caveolin-1 and the beta 1 integrin receptor and increased their association culminating in MAPK activation. Disruption of these complexes or blocking the beta 1 integrin receptor reversed these intrinsic actions of IGFBP-3. In this study we have examined the signalling pathway between integrin receptor binding and MAPK activation that mediates the intrinsic, pro-apoptotic actions of IGFBP-3. We found on inhibiting protein kinase A(PKA, Rho associated kinase (ROCK and ceramide, the accentuating effects of IGFBP-3 on apoptotic triggers were reversed, such that IGFBP-3 then conferred cell survival. We established that IGFBP-3 activated Rho, the upstream regulator of ROCK and that beta1 integrin and PKA were upstream of Rho activation, whereas the involvement of ceramide was downstream. The beta 1 integrin, PKA, Rho and ceramide were all upstream of MAPK activation. These data highlight key components involved in the pro-apoptotic effects of IGFBP-3 and that inhibiting them leads to a reversal in the action of IGFBP-3.

  3. RhoA/ROCK downregulates FPR2-mediated NADPH oxidase activation in mouse bone marrow granulocytes.

    Science.gov (United States)

    Filina, Julia V; Gabdoulkhakova, Aida G; Safronova, Valentina G

    2014-10-01

    Polymorphonuclear neutrophils (PMNs) express the high and low affinity receptors to formylated peptides (mFPR1 and mFPR2 in mice, accordingly). RhoA/ROCK (Rho activated kinase) pathway is crucial for cell motility and oxidase activity regulated via FPRs. There are contradictory data on RhoA-mediated regulation of NADPH oxidase activity in phagocytes. We have shown divergent Rho GTPases signaling via mFPR1 and mFPR2 to NADPH oxidase in PMNs from inflammatory site. The present study was aimed to find out the role of RhoA/ROCK in the respiratory burst activated via mFPR1 and mFPR2 in the bone marrow PMNs. Different kinetics of RhoA activation were detected with 0.1μM fMLF and 1μM WKYMVM operating via mFPR1 and mFPR2, accordingly. RhoA was translocated in fMLF-activated cells towards the cell center and juxtamembrane space versus uniform allocation in the resting cells. Specific inhibition of RhoA by CT04, Rho inhibitor I, weakly depressed the respiratory burst induced via mFPR1, but significantly increased the one induced via mFPR2. Inhibition of ROCK, the main effector of RhoA, by Y27632 led to the same effect on the respiratory burst. Regulation of mFPR2-induced respiratory response by ROCK was impossible under the cytoskeleton disruption by cytochalasin D, whereas it persisted in the case of mFPR1 activation. Thus we suggest RhoA to be one of the regulatory and signal transduction components in the respiratory burst through FPRs in the mouse bone marrow PMNs. Both mFPR1 and mFPR2 binding with a ligand trigger the activation of RhoA. FPR1 signaling through RhoA/ROCK increases NADPH-oxidase activity. But in FPR2 action RhoA/ROCK together with cytoskeleton-linked systems down-regulates NADPH-oxidase. This mechanism could restrain the reactive oxygen species dependent damage of own tissues during the chemotaxis of PMNs and in the resting cells. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Chiral symmetry breaking and the spin content of the {rho} and {rho}{sup '} mesons

    Energy Technology Data Exchange (ETDEWEB)

    Glozman, L.Ya., E-mail: leonid.glozman@uni-graz.at [Institut fuer Physik, FB Theoretische Physik, Universitaet Graz, A-8010 Graz (Austria); Lang, C.B., E-mail: christian.lang@uni-graz.at [Institut fuer Physik, FB Theoretische Physik, Universitaet Graz, A-8010 Graz (Austria); Limmer, M., E-mail: markus.limmer@uni-graz.at [Institut fuer Physik, FB Theoretische Physik, Universitaet Graz, A-8010 Graz (Austria)

    2011-11-03

    Using interpolators with different SU(2){sub L}xSU(2){sub R} transformation properties we study the chiral symmetry and spin contents of the {rho} and {rho}{sup '} mesons in lattice simulations with dynamical quarks. A ratio of couplings of the q-bar {gamma}{sup i}{tau}q and q-bar {sigma}{sup 0}i{tau}q interpolators to a given meson state at different resolution scales tells one about the degree of chiral symmetry breaking in the meson wave function at these scales. Using a Gaussian gauge invariant smearing of the quark fields in the interpolators, we are able to extract the chiral content of mesons up to the infrared resolution of {approx}1 fm. In the ground state {rho} meson the chiral symmetry is strongly broken with comparable contributions of both the (0,1)+(1,0) and (1/2,1/2){sub b} chiral representations with the former being the leading contribution. In contrast, in the {rho}{sup '} meson the degree of chiral symmetry breaking is manifestly smaller and the leading representation is (1/2,1/2){sub b}. Using a unitary transformation from the chiral basis to the {sup 2S+1}L{sub J} basis, we are able to define and measure the angular momentum content of mesons in the rest frame. This definition is different from the traditional one which uses parton distributions in the infinite momentum frame. The {rho} meson is practically a {sup 3}S{sub 1} state with no obvious trace of a 'spin crisis'. The {rho}{sup '} meson has a sizeable contribution of the {sup 3}D{sub 1} wave, which implies that the {rho}{sup '} meson cannot be considered as a pure radial excitation of the {rho} meson.

  5. Effect of spark plug and fuel injector location on mixture stratification in a GDI engine - A CFD analysis

    Science.gov (United States)

    Saw, O. P.; Mallikarjuna, J. M.

    2017-09-01

    The mixture preparation in gasoline direct injection (GDI) engines operating at stratified condition plays an important role in deciding the combustion, performance and emission characteristics of the engine. In a wall-guided GDI engine, with a late fuel injection strategy, piston top surface is designed in such a way that the injected fuel is directed towards the spark plug to form a combustible mixture at the time of ignition. In addition, in these engines, location of spark-plug and fuel injector, fuel injection pressure and timing are also important to create a combustible mixture near the spark plug. Therefore, understanding the mixture formation under the influence of the location of spark plug and fuel injector is very essential for the optimization of the engine parameters. In this study, an attempt is made to understand the effect of spark plug and fuel injector location on the mixture preparation in a four-stroke, four-valve and wall-guided GDI engine operating under a stratified condition by using computational fluid dynamics (CFD) analysis. All the CFD simulations are carried out at an engine speed of 2000 rev/min., and compression ratio of 10.6, at an overall equivalence ratio (ER) of about 0.65. The fuel injection and spark timings are maintained at 605 and 710 CADs respectively. Finally, it is concluded that, combination of central spark plug and side fuel injector results in better combustion and performance.

  6. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2006-01-01

    ... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

  7. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2005-01-01

    ... nucleotide exchange factors (RhoGEFs). We have developed a high throughput screening strategy identify novel inhibitors of Rho activation are currently following up on several compounds which appear to selectively inhibit Rho activation. These compounds may form the basis of future drug development strategies for the treatment of metastatic breast cancer.

  8. Measurement of Exclusive $\\rho^0 \\rho^0$ Production in Two-Photon Collisions at High $Q^2$ at LEP

    CERN Document Server

    Achard, P.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Anderhub, H.; Andreev, Valery P.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, G.; Baksay, L.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bottai, S.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.; Casaus, J.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Chamizo, M.; Chang, Y.H.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; de la Cruz, B.; Cucciarelli, S.; van Dalen, J.A.; de Asmundis, R.; Deglon, P.; Debreczeni, J.; Degre, A.; Dehmelt, K.; Deiters, K.; della Volpe, D.; Delmeire, E.; Denes, P.; DeNotaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; Dionisi, C.; Dittmar, M.; Doria, A.; Dova, M.T.; Duchesneau, D.; Duda, M.; Echenard, B.; Eline, A.; El Hage, A.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Extermann, P.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisher, W.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gentile, S.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; van Gulik, R.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hirschfelder, J.; Hofer, H.; Hohlmann, M.; Holzner, G.; Hou, S.R.; Hu, Y.; Jin, B.N.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Kafer, D.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, J.K.; Kirkby, Jasper; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Le Goff, J.M.; Leiste, R.; Levtchenko, M.; Levtchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Luci, C.; Luminari, L.; Lustermann, W.; Ma, W.G.; Malgeri, L.; Malinin, A.; Mana, C.; Mans, J.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Nagy, S.; Natale, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Nisati, A.; Novak, T.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Pal, I.; Palomares, C.; Paolucci, P.; Paramatti, R.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Petersen, B.; Piccolo, D.; Pierella, F.; Pioppi, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Pothier, J.; Prokofev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, Mohammad Azizur; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Roe, B.P.; Romero, L.; Rosca, A.; Rosier-Lees, S.; Roth, Stefan; Rosenbleck, C.; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Sakharov, A.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Schafer, C.; Schegelsky, V.; Schopper, H.; Schotanus, D.J.; Sciacca, C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Son, D.; Souga, C.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Tang, X.W.; Tarjan, P.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, Samuel C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Ulbricht, J.; Valente, E.; Van de Walle, R.T.; Vasquez, R.; Veszpremi, V.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopianov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobyov, A.A.; Wadhwa, M.; Wang, Q.; Wang, X.L.; Wang, Z.M.; Weber, M.; Wienemann, P.; Wilkens, H.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Yeh, S.C.; Zalite, An.; Zalite, Yu.; Zhang, Z.P.; Zhao, J.; Zhu, G.Y.; Zhu, R.Y.; Zhuang, H.L.; Zichichi, A.; Zimmermann, B.; Zoller, M.

    2003-01-01

    Exclusive rho rho production in two-photon collisions involving a single highly virtual photon is studied with data collected at LEP at centre-of-mass energies 89GeV rho rho is determined as a function of the photon virtuality, Q^2 and the two-photon centre-of-mass energy, Wgg, in the kinematic region: 1.2GeV^2 < Q^2 < 30GeV^2 and 1.1GeV < Wgg < 3GeV.

  9. A measurement of the branching ratio Σ+→rhoγ/Σ+→rhoπ0

    International Nuclear Information System (INIS)

    1985-06-01

    In an experiment performed in the CERN SPS hyperon beam a value for the branching ratio, Σ + →rhoγ/Σ + →rhoπ 0 of (2.46 sub(-0.35)sup(+0.30))x10 -3 , has been obtained corresponding to a branching ratio Σ + →rhoγ/Σ + → all of (1.27 sub(-0.18)sup(+0.16))x10 -3 . This result is discussed in the context of present understanding of hyperon radiative decays. (author)

  10. BFKL resummation effects in gamma* gamma* to rho rho

    Energy Technology Data Exchange (ETDEWEB)

    Enberg, R.; Pire, B.; Szymanowski, L.; Wallon, S.

    2005-08-11

    We calculate the leading order BFKL amplitude for the exclusive diffractive process {gamma}*{sub L}(Q{sub 1}{sup 2}) {gamma}*{sub L}(Q{sub 2}{sup 2}) {yields} {rho}{sub L}{sup 0}{rho}{sub L}{sup 0} in the forward direction, which can be studied in future high energy e{sup +}e{sup -} linear colliders. The resummation effects are very large compared to the fixed-order calculation. We also estimate the next-to-leading logarithmic corrections to the amplitude by using a specific resummation of higher order effects and find a substantial growth with energy, but smaller than in the leading logarithmic approximation.

  11. RhoA–Rho kinase and Platelet Activating Factor Stimulation of Ovine Fetal Pulmonary Vascular Smooth Muscle Cell Proliferation

    Science.gov (United States)

    Renteria, Lissette S.; Austin, Monique; Lazaro, Mariecon; Andrews, Mari Ashley; Lustina, Jennessee; Raj, J. Usha; Ibe, Basil O.

    2013-01-01

    Objectives Platelet Activating Factor (PAF) is produced by pulmonary vascular smooth muscle Cells (PVSMC). We studied effect of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand a role for RhoA/Rho kinase on PAF-induced ovine fetal pulmonary vascular remodeling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signaling, to induce arterial (SMC-PA) and venous (SMC-PV) growth in the hypoxic lung environment of the fetus in utero. Materials and methods Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell growth and PAFR expression were studied by DNA synthesis, Western and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation was also studied. Results Hypoxia increased PVSMC proliferation and the Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly down-regulated in both cell types by both Y-27632 and HA-1077 with comparable profiles. Also cells treated with Y-27632 showed less PAF receptor fluorescence with significant disruption of the cell morphology. Conclusions Our results show that Rho kinase nonspecifically modulates PAFR-mediated responses via a translational modification of PAFR protein and suggest that, in vivo, activation of Rho kinase by PAF may be one other pathway to sustain PAFR-mediated PVSMC growth. PMID:24033386

  12. RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation.

    Science.gov (United States)

    Renteria, L S; Austin, M; Lazaro, M; Andrews, M A; Lustina, J; Raj, J U; Ibe, B O

    2013-10-01

    Platelet-activating factor (PAF) is produced by pulmonary vascular smooth muscle cells (PVSMC). We studied effects of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand the role of RhoA/Rho kinase on PAF-induced ovine foetal pulmonary vascular remodelling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signals, to induce arterial (SMC-PA) and venous (SMC-PV) cell proliferation in the hypoxic lung environment of the foetus, in utero. Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell population expansion, and PAFR expression, were studied by DNA synthesis, western blot analysis and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation were also investigated. Hypoxia increased PVSMC proliferation and Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly downregulated in both cell types by both Y-27632 and HA-1077, with comparable profiles. Also, cells treated with Y-27632 had less PAF receptor fluorescence with significant disruption of cell morphology. Our results show that Rho kinase non-specifically modulated PAFR-mediated responses by a translational modification of PAFR protein, and suggest that, in vivo, activation of Rho kinase by PAF may be a further pathway to sustain PAFR-mediated PVSMC proliferation. © 2013 John Wiley & Sons Ltd.

  13. A Conserved RhoGAP Limits M-phase Contractility and Coordinates with Microtubule Asters to Restrict Active RhoA to the Cell Equator During Cytokinesis

    Science.gov (United States)

    Zanin, Esther; Desai, Arshad; Poser, Ina; Toyoda, Yusuke; Andree, Cordula; Moebius, Claudia; Bickle, Marc; Conradt, Barbara; Piekny, Alisa; Oegema, Karen

    2014-01-01

    SUMMARY During animal cell cytokinesis, the spindle directs contractile ring assembly by activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone dimensions. Testing the significance of RhoA flux has been hampered by the fact that the GAP targeting RhoA is not known. Here, we identify M-phase GAP (MP-GAP) as the primary GAP targeting RhoA during mitosis/cytokinesis. MP-GAP inhibition caused excessive RhoA activation in M-phase leading to the uncontrolled formation of large cortical protrusions and late cytokinesis failure. RhoA zone width was broadened by attenuation of the centrosomal asters but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery. These results identify the major GAP restraining RhoA during cell division and delineate the relative contributions of RhoA flux and centrosomal asters in controlling RhoA zone dimensions. PMID:24012485

  14. RhoA and RhoC are involved in stromal cell-derived factor-1-induced cell migration by regulating F-actin redistribution and assembly.

    Science.gov (United States)

    Luo, Jixian; Li, Dingyun; Wei, Dan; Wang, Xiaoguang; Wang, Lan; Zeng, Xianlu

    2017-12-01

    Stromal cell-derived factor-1 (SDF-1) signaling is important to the maintenance and progression of T-cell acute lymphoblastic leukemia by inducing chemotaxis migration. To identify the mechanism of SDF-1 signaling in the migration of T-ALL, Jurkat acute lymphoblastic leukemia cells were used. Results showed that SDF-1 induces Jurkat cell migration by F-actin redistribution and assembly, which is dependent on Rho activity. SDF-1 induced RhoA and RhoC activation, as well as reactive oxygen species (ROS) production, which was inhibited by Rho inhibitor. The Rho-dependent ROS production led to subsequent cytoskeleton redistribution and assembly in the process of migration. Additionally, RhoA and RhoC were involved in SDF-1-induced Jurkat cell migration. Taken together, we found a SDF-1/CXCR4-RhoA and RhoC-ROS-cytoskeleton pathway that regulates Jurkat cell migration in response to SDF-1. This work will contribute to a clearer insight into the migration mechanism of acute lymphoblastic leukemia.

  15. Effect of piston profile on performance and emission characteristics of a GDI engine with split injection strategy - A CFD study

    Science.gov (United States)

    Karaya, Y.; Mallikarjuna, J. M.

    2017-09-01

    Gasoline direct injection (GDI) engines have gained popularity in the recent times because of lower fuel consumption and exhaust emissions. But in these engines, the mixture preparation plays an important role which affects combustion, performance and emission characteristics. The mixture preparation in turn depends mainly upon combustion chamber geometry. Therefore, in this study, an attempt has been made to understand the effect of piston profile on the performance and emission characteristics in a GDI engine. The analysis is carried out on a four-stroke wall guided GDI engine using computational fluid dynamics (CFD). The spray breakup model used is validated with the available experimental results from the literature to the extent possible. The analysis is carried out for four piston profiles viz., offset pentroof with offset bowl (OPOB), flat piston with offset bowl (FPOB), offset pentroof with offset scoop (OPOS) and inclined piston with offset bowl (IPOB) fitted in an engine equipped with a six-hole injector with the split injection ratio of 30:70. All the CFD simulations are carried out at the engine speed of 2000 rev/min., with the overall equivalence ratio of about 0.65±0.05. The performance and emission characteristics of the engine are compared while using the above piston profiles. It is found that, the OPOB piston is preferred compared to that of the other pistons because it has better in-cylinder flow, IMEP and lower HC emissions compared to that of other pistons.

  16. Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway

    International Nuclear Information System (INIS)

    Duan Weiming; Xu Yaxiang; Dong Yujin; Cao Lili; Tong Jian; Zhou Xinwen

    2013-01-01

    miR-34a is transcriptionally induced by the tumor suppressor gene p53, which is often downregulated in non-small cell lung cancer (NSCLC). To address whether the downstream signal of miR-34a is sufficient to induce apoptosis and to alter cellular radiosensitivity, a chemical synthetic miR-34a mimic was delivered into A549 and H1299 cells, with or without co-treatment of γ-irradiation. Results showed that ectopic expression of miR-34a induced dose-dependent cell growth inhibition and apoptosis in a p53-independent manner in both NSCLC cell lines. Interestingly, LyGDI was discovered as a new target gene of miR-34a, and downregulation of LyGDI promoted Rac1 activation and membrane translocation, resulting in cell apoptosis. Furthermore, restoration of miR-34a indirectly reduced cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that restoration of miR-34a expression enhances radiation-induced apoptosis, partly by suppressing the LyGDI signaling pathway, and miR-34a could possibly be used as a radiosensitizer for non-small cell lung cancer therapy. (author)

  17. Observation of the ${B^0 \\to \\rho^0 \\rho^0}$ decay from an amplitude analysis of ${B^0 \\to (\\pi^+\\pi^-)(\\pi^+\\pi^-)}$ decays

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casanova Mohr, Raimon; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gastaldi, Ugo; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Geraci, Angelo; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Gianì, Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lowdon, Peter; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz, Hugo; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skillicorn, Ian; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Sterpka, Christopher Francis; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viana Barbosa, Joao Vitor; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wiedner, Dirk; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang

    2015-01-01

    Proton-proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb$^{-1}$i, are analysed to search for the charmless ${B^0 \\to \\rho^0 \\rho^0}$ decay. More than 600 ${B^0 \\to (\\pi^+\\pi^-)(\\pi^+\\pi^-)}$ signal decays are selected and used to perform an amplitude analysis from which the ${B^0 \\to \\rho^0 \\rho^0}$ decay is observed for the first time with 7.1 standard deviations significance. The fraction of ${B^0 \\to \\rho^0 \\rho^0}$ decays yielding a longitudinally polarised final state is measured to be $fL = 0.745^{+0.048}_{-0.058} ({\\rm stat}) \\pm 0.034 ({\\rm syst})$. The ${B^0 \\to \\rho^0 \\rho^0}$ branching fraction, using the ${B^0 \\to \\phi K^*(892)^{0}}$ decay as reference, is also reported as $\\mathcal B (B^0 \\to \\rho^0 \\rho^0) = (0.94 \\pm 0.17 ({\\rm stat}) \\pm 0.09 ({\\rm syst}) \\pm 0.06 ({\\rm BF})) \\times 10^{-6}$.

  18. Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

    Science.gov (United States)

    Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

    2017-05-01

    Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

  19. Rac1 and RhoA: Networks, loops and bistability.

    Science.gov (United States)

    Nguyen, Lan K; Kholodenko, Boris N; von Kriegsheim, Alex

    2016-08-17

    Cell migration requires a precise temporal and spatial coordination of several processes which allow the cell to efficiently move. The extension and retraction of membrane protrusion, as well as adhesion are controlled by the Rho-family small GTPases. Two members of the family, Rac1 and RhoA, can show opposite behaviors and spatial localisations, with RhoA being active toward the rear of the cell and regulating its retraction during migration, whereas Rac1 is active toward the front of the cell. In addition to the spatial segregation, RhoA and Rac1 activity at the leading edge of the cells has an element of temporal segregation, with RhoA and Rac1 activities peaking at separate points during the migratory cycle of protrusion and retraction. Elements of this separation have been explained by the presence of 2 mutually inhibitory feedbacks, where Rac1 inhibits RhoA and RhoA in turn can inhibit Rac1. Recently, it was shown that Rac1 and RhoA activity and downstream signaling respond in a bistable manner to perturbations of this network.

  20. BFKL resummation effects in {gamma}{sup *}{gamma}{sup *}{yields}{rho}{rho}

    Energy Technology Data Exchange (ETDEWEB)

    Enberg, R. [Ecole Polytechnique, CPHT, Palaiseau (France); Lawrence Berkeley National Laboratory, Berkeley (United States); Pire, B. [Ecole Polytechnique, CPHT, Palaiseau (France); Szymanowski, L. [Soltan Institute for Nuclear Studies, Warsaw (Poland); Universite de Liege, Liege (Belgium); Wallon, S. [LPT, Universite Paris-Sud, Orsay (France)

    2006-03-15

    We calculate the leading order BFKL amplitude for the exclusive diffractive process {gamma}{sup *}{sub L}(Q{sub 1}{sup 2}){gamma}{sup *}{sub L}(Q{sub 2}{sup 2}){yields}{rho}{sub L}{sup 0}{rho}{sub L}{sup 0} in the forward direction, which can be studied in future high energy e{sup +}e{sup -} linear colliders. The resummation effects are very large compared to the fixed-order calculation. We also estimate the next-to-leading logarithmic corrections to the amplitude by using a specific resummation of higher order effects and find a substantial growth with energy, but smaller than in the leading logarithmic approximation. (orig.)

  1. Protein kinase C-α signals P115RhoGEF phosphorylation and RhoA activation in TNF-α-induced mouse brain microvascular endothelial cell barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Deng Xiaolu

    2011-04-01

    Full Text Available Abstract Background Tumor necrosis factor-α (TNF-α, a proinflammatory cytokine, is capable of activating the small GTPase RhoA, which in turn contributes to endothelial barrier dysfunction. However, the underlying signaling mechanisms remained undefined. Therefore, we aimed to determine the role of protein kinase C (PKC isozymes in the mechanism of RhoA activation and in signaling TNF-α-induced mouse brain microvascular endothelial cell (BMEC barrier dysfunction. Methods Bend.3 cells, an immortalized mouse brain endothelial cell line, were exposed to TNF-α (10 ng/mL. RhoA activity was assessed by pull down assay. PKC-α activity was measured using enzyme assasy. BMEC barrier function was measured by transendothelial electrical resistance (TER. p115RhoGEF phosphorylation was detected by autoradiography followed by western blotting. F-actin organization was observed by rhodamine-phalloidin staining. Both pharmacological inhibitors and knockdown approaches were employed to investigate the role of PKC and p115RhoGEF in TNF-α-induced RhoA activation and BMEC permeability. Results We observed that TNF-α induces a rapid phosphorylation of p115RhoGEF, activation of PKC and RhoA in BMECs. Inhibition of conventional PKC by Gö6976 mitigated the TNF-α-induced p115RhoGEF phosphorylation and RhoA activation. Subsequently, we found that these events are regulated by PKC-α rather than PKC-β by using shRNA. In addition, P115-shRNA and n19RhoA (dominant negative mutant of RhoA transfections had no effect on mediating TNF-α-induced PKC-α activation. These data suggest that PKC-α but not PKC-β acts as an upstream regulator of p115RhoGEF phosphorylation and RhoA activation in response to TNF-α. Moreover, depletion of PKC-α, of p115RhoGEF, and inhibition of RhoA activation also prevented TNF-α-induced stress fiber formation and a decrease in TER. Conclusions Taken together, our results show that PKC-α phosphorylation of p115RhoGEF mediates TNF

  2. Exclusive {rho}{sup 0} production at HERMES

    Energy Technology Data Exchange (ETDEWEB)

    Rostomyan, Armine Armand

    2008-11-15

    In this thesis the exclusive electroproduction of {rho}{sup 0} mesons is analyzed using the data accumulated with the HERMES spectrometer in the years 2002-2005 by scattering the lepton beam of the HERA accelerator of the internal target of HERMES filled with transversely polarized hydrogen gas atoms. The {rho}{sup 0} production mechanism and, in a model-dependent way, the structure of the nucleon are studied by measuring the spin-density matrix elements (SDMEs), which parameterize the {rho}{sup 0} production and decay angular distribution. The decomposition of the angular distribution in terms of SDMEs was previously done for both polarized and unpolarized lepton beam and unpolarized target. Recently, the angular distribution was decomposed in terms of SDMEs also for a transversely polarized target. A first measurement of the 30 'transverse' SDMEs is reported in this thesis, yielding information on the degree of s-channel helicity conservation and natural-parity exchange in the case of a transversely polarized target. The measured SDMEs are implemented into the rhoMC Monte Carlo generator, which is currently the only one capable of fully simulating the exclusive {rho}{sup 0} production and decay for both unpolarized and polarized beam and target. The interest in SDMEs for a polarized target arose after it was shown that at leading twist the corresponding SDMEs can be related to the azimuthal transverse target-spin asymmetry in the cross section of exclusive {rho}{sup 0} production which is sensitive to the unknown nucleon helicity-ip GPDs. Since the GPD formalism is only valid for longitudinally polarized vector mesons produced by longitudinal photons, for the first time the transverse target-spin asymmetry of longitudinally polarized {rho}{sup 0} mesons is extracted and compared to the available theoretical predictions, specically considering possible problems with next-to-leading order corrections. (orig.)

  3. Exclusive {rho}{sup 0} production at HERMES

    Energy Technology Data Exchange (ETDEWEB)

    Rostomyan, Armine Armand

    2008-11-15

    In this thesis the exclusive electroproduction of {rho}{sup 0} mesons is analyzed using the data accumulated with the HERMES spectrometer in the years 2002-2005 by scattering the lepton beam of the HERA accelerator of the internal target of HERMES filled with transversely polarized hydrogen gas atoms. The {rho}{sup 0} production mechanism and, in a model-dependent way, the structure of the nucleon are studied by measuring the spin-density matrix elements (SDMEs), which parameterize the {rho}{sup 0} production and decay angular distribution. The decomposition of the angular distribution in terms of SDMEs was previously done for both polarized and unpolarized lepton beam and unpolarized target. Recently, the angular distribution was decomposed in terms of SDMEs also for a transversely polarized target. A first measurement of the 30 'transverse' SDMEs is reported in this thesis, yielding information on the degree of s-channel helicity conservation and natural-parity exchange in the case of a transversely polarized target. The measured SDMEs are implemented into the rhoMC Monte Carlo generator, which is currently the only one capable of fully simulating the exclusive {rho}{sup 0} production and decay for both unpolarized and polarized beam and target. The interest in SDMEs for a polarized target arose after it was shown that at leading twist the corresponding SDMEs can be related to the azimuthal transverse target-spin asymmetry in the cross section of exclusive {rho}{sup 0} production which is sensitive to the unknown nucleon helicity-ip GPDs. Since the GPD formalism is only valid for longitudinally polarized vector mesons produced by longitudinal photons, for the first time the transverse target-spin asymmetry of longitudinally polarized {rho}{sup 0} mesons is extracted and compared to the available theoretical predictions, specically considering possible problems with next-to-leading order corrections. (orig.)

  4. Scambio, a novel guanine nucleotide exchange factor for Rho

    Directory of Open Access Journals (Sweden)

    Groffen John

    2004-04-01

    Full Text Available Abstract Background Small GTPases of the Rho family are critical regulators of various cellular functions including actin cytoskeleton organization, activation of kinase cascades and mitogenesis. For this reason, a major objective has been to understand the mechanisms of Rho GTPase regulation. Here, we examine the function of a novel protein, Scambio, which shares homology with the DH-PH domains of several known guanine nucleotide exchange factors for Rho family members. Results Scambio is located on human chromosome 14q11.1, encodes a protein of around 181 kDa, and is highly expressed in both heart and skeletal muscle. In contrast to most DH-PH-domain containing proteins, it binds the activated, GTP-bound forms of Rac and Cdc42. However, it fails to associate with V14RhoA. Immunofluorescence studies indicate that Scambio and activated Rac3 colocalize in membrane ruffles at the cell periphery. In accordance with these findings, Scambio does not activate either Rac or Cdc42 but rather, stimulates guanine nucleotide exchange on RhoA and its close relative, RhoC. Conclusion Scambio associates with Rac in its activated conformation and functions as a guanine nucleotide exchange factor for Rho.

  5. The rho-parameter in supersymmetric models

    International Nuclear Information System (INIS)

    Lim, C.S.; Inami, T.; Sakai, N.

    1983-10-01

    The electroweak rho-parameter is examined in a general class of supersymmetric models. Formulae are given for one-loop contributions to Δrho from scalar quarks and leptons, gauge-Higgs fermions and an extra doublet of Higgs scalars. Mass differences between members of isodoublet scalar quarks and leptons are constrained to be less than about 200 GeV. (author)

  6. Effect of electroacupuncture on the mRNA and protein expression of Rho-A and Rho-associated kinase II in spinal cord injury rats

    Directory of Open Access Journals (Sweden)

    You-jiang Min

    2017-01-01

    Full Text Available Electroacupuncture is beneficial for the recovery of spinal cord injury, but the underlying mechanism is unclear. The Rho/Rho-associated kinase (ROCK signaling pathway regulates the actin cytoskeleton by controlling the adhesive and migratory behaviors of cells that could inhibit neurite regrowth after neural injury and consequently hinder the recovery from spinal cord injury. Therefore, we hypothesized electroacupuncture could affect the Rho/ROCK signaling pathway to promote the recovery of spinal cord injury. In our experiments, the spinal cord injury in adult Sprague-Dawley rats was caused by an impact device. Those rats were subjected to electroacupuncture at Yaoyangguan (GV3, Dazhui (GV14, Zusanli (ST36 and Ciliao (BL32 and/or monosialoganglioside treatment. Behavioral scores revealed that the hindlimb motor functions improved with those treatments. Real-time quantitative polymerase chain reaction, fluorescence in situ hybridization and western blot assay showed that electroacupuncture suppressed the mRNA and protein expression of Rho-A and Rho-associated kinase II (ROCKII of injured spinal cord. Although monosialoganglioside promoted the recovery of hindlimb motor function, monosialoganglioside did not affect the expression of Rho-A and ROCKII. However, electroacupuncture combined with monosialoganglioside did not further improve the motor function or suppress the expression of Rho-A and ROCKII. Our data suggested that the electroacupuncture could specifically inhibit the activation of the Rho/ROCK signaling pathway thus partially contributing to the repair of injured spinal cord. Monosialoganglioside could promote the motor function but did not suppress expression of RhoA and ROCKII. There was no synergistic effect of electroacupuncture combined with monosialoganglioside.

  7. gsub(ωrhoπ) coupling constant from QCD sum rules

    International Nuclear Information System (INIS)

    Eletsky, V.L.; Ioffe, B.L.; Kogan, Ya.I.

    1982-01-01

    QCD sum rules for the vertex function of two vector and one axial vector currents are used to calculate the gsub(ωrhoπ) coupling constant (where gsub(ωrhoπ) is a transition coupling constant for ω → rhoπ process). The obtained value, gsub(ωrhoπ) approximately 17 GeV -1 is in a good agreement with experimental data

  8. Double spin asymmetry in exclusive $\\rho^0$ muoproduction at COMPASS

    CERN Document Server

    Alexakhin, V Yu; Alexandrov, Yu A; Alexeev, G D; Amoroso, A; Arbuzov, A; Badelek, B; Balestra, F; Ball, J; Baum, G; Barth, J; Bedfer, Y; Bernet, C; Bertini, R; Bettinelli, M; Birsa, R; Bisplinghoff, J; Bordalo, P; Bradamante, Franco; Bravar, A; Bressan, A; Brona, G; Burtin, E; Bussa, M P; Chapiro, A; Chiosso, M; Cicuttin, A; Colantoni, M L; Costa, S; Crespo, M L; D'Hose, N; Dalla Torre, S; Das, S; Das-Gupta, S S; De Masi, R; Dedek, N; Denisov, O Yu; Dhara, L; Díaz, V; Dinkelbach, A M; Donskov, S V; Dorofeev, V A; Doshita, N; Duic, V; Dünnweber, W; Eversheim, P D; Eyrich, W; Fabro, M; Faessler, M; Falaleev, V; Ferrero, A; Ferrero, L; Finger, M; Finger, M Jr; Fischer, H; Franco, C; Franz, J; Friedrich, J M; Frolov, V; Garfagnini, R; Gautheron, F; Gavrichtchouk, O P; Gazda, R; Gerassimov, S G; Geyer, R; Giorgi, M; Gobbo, B; Görtz, S; Gorin, A M; Grabmuller, S; Grajek, O A; Grasso, A; Grube, B; Gushterski, R; Guskov, A; Haas, F; Hannappel, J; Von Harrach, D; Hasegawa, T; Heckmann, J; Hedicke, S; Heinsius, F H; Hermann, R; Hess, C; Hinterberger, F; Von Hodenberg, M; Horikawa, N; Horikawa, S; Ilgner, C; Ioukaev, A I; Ishimoto, S; Ivanov, O; Ivanshin, Yu; Iwata, T; Jahn, R; Janata, A; Jasinski, P; Joosten, R; Jouravlev, N I; Kabuss, E M; Kang, D; Ketzer, B; Khaustov, G V; Khokhlov, Yu A; Kisselev, Yu; Klein, F; Klimaszewski, K; Koblitz, S; Koivuniemi, J H; Kolosov, V N; Komissarov, E V; Kondo, K; Knigsmann, K; Konorov, I; Konstantinov, V F; Korentchenko, A S; Korzenev, A; Kotzinian, A M; Koutchinski, N A; Kuznetsov, O; Kravchuk, N P; Kral, A; Kroumchtein, Z V; Kühn, R; Kunne, Fabienne; Kurek, K; Ladygin, M E; Lamanna, M; Le Goff, J M; Lednev, A A; Lehmann, A; Lichtenstadt, J; Liska, T; Ludwig, I; Maggiora, A; Maggiora, M; Magnon, A; Mallot, G K; Mann, A; Marchand, C; Marroncle, J; Martin, A; Marzec, J; Massmann, F; Matsuda, T; Maksimov, A N; Meyer, W; Mielech, A; Mikhailov, Yu V; Moinester, M A; Mutter, A; Nahle, O; Nagaytsev, A; Nagel, T; Nassalski, J P; Neliba, S; Nerling, F; Neubert, a S; Neyret, D P; Nikolaenko, V I; Nikolaev, K; Olshevskii, A G; Ostrick, M; Padee, A; Pagano, P; Panebianco, S; Panknin, R; Panzieri, D; Paul, S; Pawlukiewicz-Kaminska, B; Peshekhonov, V D; Piragino, G; Platchkov, S; Pochodzalla, J; Polak, J; Polyakov, V A; Pretz, J; Procureur, S; Quintans, C; Rajotte, J F; Rapatsky, V; Ramos, S; Reicherz, G; Richter, A; Robinet, F; Rocco, E; Rondio, E; Rozhdestvensky, A M; Ryabchikov, D I; Samoylenko, V D; Sandacz, A; Santos, H; Sapozhnikov, M G; Sarkar, S; Savin, I A; Schiavon, Paolo; Schill, C; Schmitt, L; Schonmeier, P; Schroder, W; Shevchenko, O Yu; Siebert, H W; Silva, L; Sinha, L; Sissakian, A N; Slunecka, M; Smirnov, G I; Sosio, S; Sozzi, F; Sugonyaev, V P; Srnka, A; Stinzing, F; Stolarski, M; Sulc, M; Sulej, R; Takabayashi, N; Tchalishev, V V; Tessaro, S; Tessarotto, F; Teufel, A; Tkatchev, L G; Venugopal, G; Virius, M; Vlassov, N V; Vossen, A; Webb, R; Weise, E; Weitzel, Q; Windmolders, R; Wirth, S; Wilicki, W; Zaremba, s K; Zavertyaev, M; Zemlyanichkina, E; Zhao, J; Ziegler, R; Zvyagin, A

    2007-01-01

    The longitudinal double spin asymmetry A_1^rho for exclusive leptoproduction of rho^0 mesons, mu + N -> mu + N + rho, is studied using the COMPASS 2002 and 2003 data. The measured reaction is incoherent exclusive rho^0 production on polarised deuterons. The Q^2 and x dependence of A_1^rho is presented in a wide kinematical range: 3x10^-3 < Q^2 < 7 (GeV/c)^2 and 5x10^-5 < x < 0.05. The presented results are the first measurements of A_1^rho at small Q2 (Q2 < 0.1 (GeV/c)^2) and small x (x < 3x10^-3). The asymmetry is in general compatible with zero in the whole kinematical range.

  9. RhoG protein regulates platelet granule secretion and thrombus formation in mice.

    Science.gov (United States)

    Goggs, Robert; Harper, Matthew T; Pope, Robert J; Savage, Joshua S; Williams, Christopher M; Mundell, Stuart J; Heesom, Kate J; Bass, Mark; Mellor, Harry; Poole, Alastair W

    2013-11-22

    Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.

  10. Partial contribution of Rho-kinase inhibition to the bioactivity of Ganoderma lingzhi and its isolated compounds: insights on discovery of natural Rho-kinase inhibitors.

    Science.gov (United States)

    Amen, Yhiya; Zhu, Qinchang; Tran, Hai-Bang; Afifi, Mohamed S; Halim, Ahmed F; Ashour, Ahmed; Shimizu, Kuniyoshi

    2017-04-01

    Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes. The structure-activity relationship analysis was investigated. Our results suggest that the traditional uses of G. lingzhi might be in part due to the ROCK-I and ROCK-II inhibitory potential of this mushroom. Structure-activity relationship studies revealed some interesting features of the lanostane triterpenes that potentiate their Rho-kinase inhibition. These findings would be helpful for further studies on the design of Rho-kinase inhibitors from natural sources and open the door for contributions from other researchers for optimizing the development of natural Rho-kinase inhibitors.

  11. Grb2 mediates semaphorin-4D-dependent RhoA inactivation.

    Science.gov (United States)

    Sun, Tianliang; Krishnan, Rameshkumar; Swiercz, Jakub M

    2012-08-01

    Signaling through the semaphorin 4D (Sema4D) receptor plexin-B1 is modulated by its interaction with tyrosine kinases ErbB-2 and Met. In cells expressing the plexin-B1-ErbB-2 receptor complex, ligand stimulation results in the activation of small GTPase RhoA and stimulation of cellular migration. By contrast, in cells expressing plexin-B1 and Met, ligand stimulation results in an association with the RhoGTPase-activating protein p190 RhoGAP and subsequent RhoA inactivation--a process that involves the tyrosine phosphorylation of plexin-B1 by Met. Inactivation of RhoA is necessary for Sema4D-mediated inhibition of cellular migration. It is, however, unknown how plexin-B1 phosphorylation regulates RhoGAP interaction and activity. Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Grb2 is thereby recruited into the plexin-B1 receptor complex and, through its SH3 domain, interacts with p190 RhoGAP and mediates RhoA deactivation. Phosphorylation of plexin-B1 by Met and the recruitment of Grb2 have no effect on the R-RasGAP activity of plexin-B1, but are required for Sema4D-induced, RhoA-dependent antimigratory effects of Sema4D on breast cancer cells. These data show Grb2 as a direct link between plexin and p190-RhoGAP-mediated downstream signaling.

  12. etaγ decays of rho0, ω, and phi mesons

    International Nuclear Information System (INIS)

    Andrews, D.E.; Fukushima, Y.; Harvey, J.; Lobkowicz, F.; May, E.N.; Nelson, C.A. Jr.; Thorndike, E.H.

    1977-01-01

    etaγ decays of rho 0 , ω, and phi are studied. We find GAMMA (phi→etaγ) =55 +- 12 keV. Our data admit two solutions for (rho 0 , ω) →etaγ: Either GAMMA (rho 0 →etaγ) =50 +- 13 keV, GAMMA (ω→etaγ) =3.0 +2 /sup ./ 5 /sub -/ 1 /sub ./ 8 keV, and the (ω,rho) →etaγ relative decay phase is near zero; or GAMMA (rho 0 →etaγ) =76 +- 15 keV, GAMMA (ω→etaγ) =29 +- 7 keV, and the decay phase is near 180degree

  13. Rab-GDI complex dissociation factor expressed through translational frameshifting in filamentous ascomycetes.

    Directory of Open Access Journals (Sweden)

    Fabienne Malagnac

    Full Text Available In the model fungus Podospora anserina, the PaYIP3 gene encoding the orthologue of the Saccharomyces cerevisiae YIP3 Rab-GDI complex dissociation factor expresses two polypeptides, one of which, the long form, is produced through a programmed translation frameshift. Inactivation of PaYIP3 results in slightly delayed growth associated with modification in repartition of fruiting body on the thallus, along with reduced ascospore production on wood. Long and short forms of PaYIP3 are expressed in the mycelium, while only the short form appears expressed in the maturing fruiting body (perithecium. The frameshift has been conserved over the evolution of the Pezizomycotina, lasting for over 400 million years, suggesting that it has an important role in the wild.

  14. Rab-GDI complex dissociation factor expressed through translational frameshifting in filamentous ascomycetes.

    Science.gov (United States)

    Malagnac, Fabienne; Fabret, Céline; Prigent, Magali; Rousset, Jean-Pierre; Namy, Olivier; Silar, Philippe

    2013-01-01

    In the model fungus Podospora anserina, the PaYIP3 gene encoding the orthologue of the Saccharomyces cerevisiae YIP3 Rab-GDI complex dissociation factor expresses two polypeptides, one of which, the long form, is produced through a programmed translation frameshift. Inactivation of PaYIP3 results in slightly delayed growth associated with modification in repartition of fruiting body on the thallus, along with reduced ascospore production on wood. Long and short forms of PaYIP3 are expressed in the mycelium, while only the short form appears expressed in the maturing fruiting body (perithecium). The frameshift has been conserved over the evolution of the Pezizomycotina, lasting for over 400 million years, suggesting that it has an important role in the wild.

  15. Control of harmful hydrocarbon species in the exhaust of modern advanced GDI engines

    Science.gov (United States)

    Hasan, A. O.; Abu-jrai, A.; Turner, D.; Tsolakis, A.; Xu, H. M.; Golunski, S. E.; Herreros, J. M.

    2016-03-01

    A qualitative and quantitative analysis of toxic but currently non-regulated hydrocarbon compounds ranging from C5-C11, before and after a zoned three-way catalytic converter (TWC) in a modern gasoline direct injection (GDI) engine has been studied using gas chromatography-mass spectrometry (GC-MS). The GDI engine has been operated under conventional and advanced combustion modes, which result in better fuel economy and reduced levels of NOx with respect to standard SI operation. However, these fuel-efficient conditions are more challenging for the operation of a conventional TWC, and could lead to higher level of emissions released to the environment. Lean combustion leads to the reduction in pumping losses, fuel consumption and in-cylinder emission formation rates. However, lean HCCI will lead to high levels of unburnt HCs while the presence of oxygen will lower the TWC efficiency for NOx control. The effect on the catalytic conversion of the hydrocarbon species of the addition of hydrogen upstream the catalyst has been also investigated. The highest hydrocarbon engine-out emissions were produced for HCCI engine operation at low engine load operation. The catalyst was able to remove most of the hydrocarbon species to low levels (below the permissible exposure limits) for standard and most of the advanced combustion modes, except for naphthalene (classified as possibly carcinogenic to humans by the International Agency for Research on Cancer) and methyl-naphthalene (which has the potential to cause lung damage). However, when hydrogen was added upstream of the catalyst, the catalyst conversion efficiency in reducing methyl-naphthalene and naphthalene was increased by approximately 21%. This results in simultaneous fuel economy and environmental benefits from the effective combination of advanced combustion and novel aftertreatment systems.

  16. 1α,25-Dihydroxyvitamin D3 Ameliorates Seawater Aspiration-Induced Acute Lung Injury via NF-κB and RhoA/Rho Kinase Pathways

    Science.gov (United States)

    Liu, Wei; Wang, Li; Luo, Ying; Li, Zhichao; Jin, Faguang

    2014-01-01

    Introduction Inflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses inflammation, it has not been confirmed to be effective in seawater aspiration-induced ALI. Thus, we investigated the effect of calcitriol on seawater aspiration-induced ALI and explored the probable mechanism. Methods Male SD rats receiving different doses of calcitriol or not, underwent seawater instillation. Then lung samples were collected at 4 h for analysis. In addition, A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not and then stimulated with 25% seawater for 40 min. After these treatments, cells samples were collected for analysis. Results Results from real-time PCR showed that seawater stimulation up-regulated the expression of vitamin D receptor in lung tissues, A549 cells and RPMVECs. Seawater stimulation also activates NF-κB and RhoA/Rho kinase pathways. However, we found that pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways. Meanwhile, treatment of calcitriol also improved lung histopathologic changes, reduced inflammation, lung edema and vascular leakage. Conclusions These results demonstrated that NF-κB and RhoA/Rho kinase pathways are critical in the development of lung inflammation and pulmonary edema and that treatment with calcitriol could ameliorate seawater aspiration-induced ALI, which was probably through the inhibition of NF-κB and RhoA/Rho kinase pathways. PMID:25118599

  17. RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer.

    Science.gov (United States)

    Vishnu, Prakash; Colon-Otero, Gerardo; Kennedy, Gregory T; Marlow, Laura A; Kennedy, William P; Wu, Kevin J; Santoso, Joseph T; Copland, John A

    2012-03-01

    The aim was to evaluate antitumor activity of the combination of ixabepilone and sunitinib in pre-clinical models of chemotherapy naïve and refractory epithelial ovarian tumors, and to investigate the mechanism of synergy of such drug combination. HOVTAX2 cell line was derived from a metastatic serous papillary epithelial ovarian tumor (EOC) and a paclitaxel-resistant derivative was established. Dose response curves for ixabepilone and sunitinib were generated and synergy was determined using combination indexes. The molecular mechanism of antitumor synergy was examined using shRNA silencing. The combination of ixabepilone and sunitinib demonstrated robust antitumor synergy in naïve and paclitaxel-resistant HOVTAX2 cell lines due to increased apoptosis. The GTPase, RhoB, was synergistically upregulated in cells treated with ixabepilone and sunitinib. Using shRNA, RhoB was demonstrated to mediate antitumor synergy. These results were validated in two other EOC cell lines. Ixabepilone plus sunitinib demonstrated antitumor synergy via RhoB in naïve and paclitaxel-resistant cells resulting in apoptosis. This study demonstrates a novel mechanism of action leading to antitumor synergy and provides 'proof-of-principle' for combining molecular targeted agents with cytotoxic chemotherapy to improve antitumor efficacy. RhoB could be envisioned as an early biomarker of response to therapy in a planned Phase II clinical trial to assess the efficacy of ixabepilone combined with a receptor tyrosine kinase inhibitor such as sunitinib. To the best of our knowledge, this is the first demonstration of antitumor synergy between these two classes of drugs in EOC and the pivotal role of RhoB in this synergy. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Measurement of branching rates and search for CP violation in decays B0 {yields} {rho} {pi}, {rho} K; Mesure des rapports d'embranchement et recherche de la violation de CP dans les modes B{sup 0}{yields}rhopi, rhoK

    Energy Technology Data Exchange (ETDEWEB)

    Laplace, S

    2003-04-01

    The BABAR experiment, at the PEP-II collider at SLAC, has been studying since 1999 CP violation in the B meson system. After the precise measurement of sin(2*{beta}) we are now concentrating on measuring the alpha and gamma angles of the unitarity triangle. The work presented in this thesis concerns the measurement of the alpha angle in the B{sub 0} {yields} {rho}{pi} mode. We realized a time-dependant analysis of CP and the measurements of branching ratios concerning B{sub 0} {yields} {rho}{sup +-}{pi}{sup -+} and B{sub 0} {yields} {rho}{sup -}K{sup +} modes. The results obtained on an integrated luminosity of 80.9 fb{sup -1} are the following: B(B{sub 0} {yields} {rho}{sup +-}{pi}{sup -+}) = (22.6 {+-} 1.8 {+-} 2.2) 10{sup -6}, B(B{sub 0} {yields} {rho}{sup -}K{sup +}) (7.3 {+-} 1.3 {+-} 1.3) 10{sup -6}, ACP({rho}{pi}) = -0.18 {+-} 0.08 {+-} 0.03, ACP({rho}K) = -0.28 {+-} 0.17 {+-} 0.08, C({rho}{pi}) -0.36 {+-} 0.18 {+-} 0.04, S({rho}{pi}) = -0.19 {+-} 0.24 {+-} 0.03, {delta}C({rho}{pi}) = 0.28 {+-} 0.19 {+-} 0.04, {delta}S({rho}{pi}) = 0.15 {+-} 0.25 {+-} 0.03. We also measured the branching ratio of B{sub 0} {yields} {rho}{sub 0}{pi}{sub 0} with a significance of 2.7 {sigma}. We therefore put the following upper limit at 90% CL (confidence level): B(B{sub 0} {yields} {rho}{sub 0}{pi}{sub 0}) < 2.7*10{sup -6} at 90% CL. Finally, we built the heart of a complete Dalitz plot analysis of B{sub 0} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup 0}, and estimated the experimental sensibility on alpha. The results obtained on the B{sub 0} {yields} {rho}{pi} modes are interpreted in terms of constraints on the alpha angle with methods using SU(2) and SU(3) symmetries. We also measured the branching ratio of B{sub 0} {yields} {alpha}{sub 0}{pi} using a reduced luminosity, leading to the result: B(B{sub 0} {yields} {alpha}{sub 0}{pi}) = (6.2 +3.0-2.5 {+-} 1.1)*10{sup -6}. Some phenomenological studies have been performed to infer the feasibility of a CP analysis to determine the

  19. RhoC a new target for therapeutic vaccination against metastatic cancer

    DEFF Research Database (Denmark)

    Wenandy, L.; Sorensen, R.B.; Straten, P.T.

    2008-01-01

    Most cancer deaths are due to the development of metastases. Increased expression of RhoC is linked to enhanced metastatic potential in multiple cancers. Consequently, the RhoC protein is an attractive target for drug design. The clinical application of immunotherapy against cancer is rapidly...... of cancer makes RhoC a very attractive target for anti-cancer immunotherapy. Herein, we describe an HLA-A3 restricted epitope from RhoC, which is recognized by cytotoxic T cells. Moreover, RhoC-specific T cells show cytotoxic potential against HLA-matched cancer cells of different origin. Thus, RhoC may...... moving forward in multiple areas, including the adoptive transfer of anti-tumor-reactive T cells and the use of "therapeutic" vaccines. The over-expression of RhoC in cancer and the fact that immune escape by down regulation or loss of expression of this protein would reduce the morbidity and mortality...

  20. Rho resonance parameters from lattice QCD

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Dehua; Alexandru, Andrei; Molina, Raquel; Döring, Michael

    2016-08-01

    We perform a high-precision calculation of the phase shifts for $\\pi$-$\\pi$ scattering in the I = 1, J = 1 channel in the elastic region using elongated lattices with two mass-degenerate quark favors ($N_f = 2$). We extract the $\\rho$ resonance parameters using a Breit-Wigner fit at two different quark masses, corresponding to $m_{\\pi} = 226$MeV and $m_{\\pi} = 315$MeV, and perform an extrapolation to the physical point. The extrapolation is based on a unitarized chiral perturbation theory model that describes well the phase-shifts around the resonance for both quark masses. We find that the extrapolated value, $m_{\\rho} = 720(1)(15)$MeV, is significantly lower that the physical rho mass and we argue that this shift could be due to the absence of the strange quark in our calculation.

  1. Coding sequence of human rho cDNAs clone 6 and clone 9

    Energy Technology Data Exchange (ETDEWEB)

    Chardin, P; Madaule, P; Tavitian, A

    1988-03-25

    The authors have isolated human cDNAs including the complete coding sequence for two rho proteins corresponding to the incomplete isolates previously described as clone 6 and clone 9. The deduced a.a. sequences, when compared to the a.a. sequence deduced from clone 12 cDNA, show that there are in human at least three highly homologous rho genes. They suggest that clone 12 be named rhoA, clone 6 : rhoB and clone 9 : rhoC. RhoA, B and C proteins display approx. 30% a.a. identity with ras proteins,. mainly clustered in four highly homologous internal regions corresponding to the GTP binding site; however at least one significant difference is found; the 3 rho proteins have an Alanine in position corresponding to ras Glycine 13, suggesting that rho and ras proteins might have slightly different biochemical properties.

  2. The role of Rho-kinase and calcium ions in constriction triggered by ET-1.

    Science.gov (United States)

    Wiciński, Michał; Szadujkis-Szadurska, Katarzyna; Węclewicz, Mateusz M; Malinowski, Bartosz; Matusiak, Grzegorz; Walczak, Maciej; Wódkiewicz, Eryk; Grześk, Grzegorz; Pawlak-Osińska, Katarzyna

    2018-05-05

    Endothelin-1 (ET-1) is one of the key factors regulating tension of smooth muscles in blood vessels. It is believed that ET-1 plays an important role in pathogenesis of hypertension, and cardiovascular diseases; therefore, research in order to limit ET-1-mediated action is still in progress. The main objective of this paper was to evaluate the role of Rho-kinase in the ET-1-induced constriction of arteries. The analysis also included significance of intra- and extracellular pool of calcium ions in constriction triggered by ET-1. The studies were performed on perfused Wistar rat tail arteries. Concentration response curve (CRC) was determined for ET-1 in the presence of increased concentrations of Rho-kinase inhibitor (Y-27632) and IP3-receptor antagonist (2APB), both in reference to constriction triggered by solely ET-1. Afterwards, the influence of calcium ions present in the perfusion fluid was evaluated in terms of the effect triggered by 2APB and occurring in arteries constricted by ET-1. ET-1, in concentration dependent manner, leads to increase in perfusion pressure. Y-27632 and 2APB lead to shift of the concentration response curve for ET-1 to the right with simultaneously lowered maximum effect. There was no difference in reaction of the artery constricted by ET-1 and treated with 2APB in solution containing calcium and in calcium-free solution. Vasoconstrictive action of endothelin is not significantly dependent on the inflow of extracellular calcium, but it is proportional to inflow of Ca 2+ related to activation of IP3 receptors and to Rho-kinase activity. Copyright © 2018. Published by Elsevier Inc.

  3. Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.

    Science.gov (United States)

    Morrison Joly, Meghan; Williams, Michelle M; Hicks, Donna J; Jones, Bayley; Sanchez, Violeta; Young, Christian D; Sarbassov, Dos D; Muller, William J; Brantley-Sieders, Dana; Cook, Rebecca S

    2017-06-30

    The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear. Because Rictor is an obligate cofactor of mTORC2, we genetically engineered Rictor ablation or overexpression in mouse and human HER2-amplified breast cancer models for modulation of mTORC2 activity. Signaling through mTORC2-dependent pathways was also manipulated using pharmacological inhibitors of mTOR, Akt, and Rac. Signaling was assessed by western analysis and biochemical pull-down assays specific for Rac-GTP and for active Rac guanine nucleotide exchange factors (GEFs). Metastases were assessed from spontaneous tumors and from intravenously delivered tumor cells. Motility and invasion of cells was assessed using Matrigel-coated transwell assays. We found that Rictor ablation potently impaired, while Rictor overexpression increased, metastasis in spontaneous and intravenously seeded models of HER2-overexpressing breast cancers. Additionally, migration and invasion of HER2-amplified human breast cancer cells was diminished in the absence of Rictor, or upon pharmacological mTOR kinase inhibition. Active Rac1 was required for Rictor-dependent invasion and motility, which rescued invasion/motility in Rictor depleted cells. Rictor/mTORC2-dependent dampening of the endogenous Rac1 inhibitor RhoGDI2, a factor that correlated directly with increased overall survival in HER2-amplified breast cancer patients, promoted Rac1 activity and tumor cell invasion/migration. The mTORC2 substrate Akt did not affect RhoGDI2 dampening, but partially

  4. {gamma}*{gamma}*->{rho}{rho} at very high energy

    Energy Technology Data Exchange (ETDEWEB)

    Pire, B. [CPhT, Ecole Polytechnique, 91128 Palaiseau, France, UMR 7644 du CNRS (France); Szymanowski, L. [Soltan Institute for Nuclear Studies, Hoza 69, 00-681 Warsaw (Poland) and Universite de Liege, B4000 Liege (Belgium); Wallon, S. [LPT, Universite d' Orsay, F 91405-Orsay (France); UMR 8627 du CNRS (France)

    2005-06-13

    The next generation of e{sup +}e{sup -}-colliders will offer a possibility of clean testing of QCD dynamics in the Regge limit. Recent progress in the theoretical description of exclusive processes permits for many of them a consistent use of the perturbative QCD methods. We advocate that the exclusive diffractive production of two {rho} mesons from virtual photons at very high energies should be measurable at the future linear collider (LC)

  5. Rho-associated kinase is a therapeutic target in neuroblastoma.

    Science.gov (United States)

    Dyberg, Cecilia; Fransson, Susanne; Andonova, Teodora; Sveinbjörnsson, Baldur; Lännerholm-Palm, Jessika; Olsen, Thale K; Forsberg, David; Herlenius, Eric; Martinsson, Tommy; Brodin, Bertha; Kogner, Per; Johnsen, John Inge; Wickström, Malin

    2017-08-08

    Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN -driven neuroblastoma growth in TH- MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

  6. Quasi-two-dimensional Fermi-liquid state in Sr2RhO4-δ

    International Nuclear Information System (INIS)

    Nagai, Ichiro; Shirakawa, Naoki; Umeyama, Norio; Ikeda, Shin-ichi

    2010-01-01

    Single crystals of layered perovskite Sr 2 RhO 4-δ (δ=0.0 and 0.1) are successfully grown by the floating-zone method. Stoichiometric single crystals (Sr 2 RhO 4.0 ) are obtained by O 2 -annealing the as-grown crystals (Sr 2 RhO 3.9 ). Sr 2 RhO 4.0 and Sr 2 RhO 3.9 show quasi-two-dimensional Fermi-liquid behavior at low temperatures, whereas there are large differences in the anisotropy of electrical resistivity ρ c (3 K)/ρ ab (3 K) and Wilson ratio R w between Sr 2 RhO 4.0 and Sr 2 RhO 3.9 : ρ c (3 K)/ρ ab (3 K)=2400 (19000) and R w =3.8 (6.4) for Sr 2 RhO 4.0 (Sr 2 RhO 3.9 ). The differences observed between the temperature dependence of the in-plane electrical resistivity (T 2 RhO 4.0 and Sr 2 RhO 3.9 are mainly derived from those between the density of states and band structure near the corresponding Fermi level. This indicates that the changes in these physical properties, which are accompanied by oxygen defects in the Sr 2 RhO 4-δ system, can be explained by the rigid band model. Moreover, these results suggest that t 2g band-filling can be controlled by adjusting the oxygen defect content δ in the Sr 2 RhO 4-δ system. Although many similarities are observed in this study between the physical properties of Sr 2 RhO 4.0 and Sr 2 RuO 4 . Sr 2 RhO 4.0 does not exhibit superconductivity down to 36 mK. (author)

  7. The activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 to the distal CCAAT box of the RhoB promoter

    International Nuclear Information System (INIS)

    Ahn, Jiwon; Choi, Jeong-Hae; Won, Misun; Kang, Chang-Mo; Gyun, Mi-Rang; Park, Hee-Moon; Kim, Chun-Ho; Chung, Kyung-Sook

    2011-01-01

    Highlights: → Regulation of transcriptional activation of RhoB is still unclear. → We examine the effect of p38 MAPK inhibition, and c-Jun and RhoB depletion on UV-induced RhoB expression and apoptosis. → We identify the regions of RhoB promoter necessary to confer UV responsiveness using pRhoB-luciferase reporter assays. → c-Jun, ATF2 and p300 are dominantly associated with NF-Y on the distal CCAAT box. → The activation of p38 MAPK primarily contribute to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins on distal CCAAT box of RhoB promoter. -- Abstract: The Ras-related small GTP-binding protein RhoB is rapidly induced in response to genotoxic stresses caused by ionizing radiation. It is known that UV-induced RhoB expression results from the binding of activating transcription factor 2 (ATF2) via NF-Y to the inverted CCAAT box (-23) of the RhoB promoter. Here, we show that the association of c-Jun with the distal CCAAT box (-72) is primarily involved in UV-induced RhoB expression and p38 MAPK regulated RhoB induction through the distal CCAAT box. UV-induced RhoB expression and apoptosis were markedly attenuated by pretreatment with the p38 MAPK inhibitor. siRNA knockdown of RhoB, ATF2 and c-Jun resulted in decreased RhoB expression and eventually restored the growth of UV-irradiated Jurkat cells. In the reporter assay using luciferase under the RhoB promoter, inhibition of RhoB promoter activity by the p38 inhibitor and knockdown of c-Jun using siRNA occurred through the distal CCAAT box. Immunoprecipitation and DNA affinity protein binding assays revealed the association of c-Jun and p300 via NF-YA and the dissociation of histone deacetylase 1 (HDAC1) via c-Jun recruitment to the CCAAT boxes of the RhoB promoter. These results suggest that the activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins to the distal CCAAT box of the RhoB promoter in Jurkat cells.

  8. The activation of RhoC in vascular endothelial cells is required for the S1P receptor type 2-induced inhibition of angiogenesis.

    Science.gov (United States)

    Del Galdo, Sabrina; Vettel, Christiane; Heringdorf, Dagmar Meyer Zu; Wieland, Thomas

    2013-12-01

    Sphingosine-1-phosphate (S1P) is a multifunctional phospholipid inducing a variety of cellular responses in endothelial cells (EC). S1P responses are mediated by five G protein coupled receptors of which three types (S1P1R-S1P3R) have been described to be of importance in vascular endothelial cells (EC). Whereas the S1P1R regulates endothelial barrier function by coupling to Gαi and the monomeric GTPase Rac1, the signaling pathways involved in the S1P-induced regulation of angiogenesis are ill defined. We therefore studied the sprouting of human umbilical vein EC (HUVEC) in vitro and analyzed the activation of the RhoGTPases RhoA and RhoC. Physiological relevant concentrations of S1P (100-300nM) induce a moderate activation of RhoA and RhoC. Inhibition or siRNA-mediated depletion of the S1P2R preferentially decreased the activation of RhoC. Both manipulations caused an increase of sprouting in a spheroid based in vitro sprouting assay. Interestingly, a similar increase in sprouting was detected after effective siRNA-mediated knockdown of RhoC. In contrast, the depletion of RhoA had no influence on sprouting. Furthermore, suppression of the activity of G proteins of the Gα12/13 subfamily by adenoviral overexpression of the regulator of G protein signaling domain of LSC as well as siRNA-mediated knockdown of the Rho specific guanine nucleotide exchange factor leukemia associated RhoGEF (LARG) inhibited the S1P-induced activation of RhoC and concomitantly increased sprouting of HUVEC with similar efficacy. We conclude that the angiogenic sprouting of EC is suppressed via the S1P2R subtype. Thus, the increase in basal sprouting can be attributed to blocking of the inhibitory action of autocrine S1P stimulating the S1P2R. This inhibitory pathway involves the activation of RhoC via Gα12/13 and LARG, while the simultaneously occurring activation of RhoA is apparently dispensable here. © 2013.

  9. Rho GTPases in ameloblast differentiation

    Directory of Open Access Journals (Sweden)

    Keishi Otsu

    2016-05-01

    Full Text Available During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

  10. QCD Factorizations in Exclusive {gamma}*{gamma}*{yields}{rho}{sub L}{sup 0}{rho}{sub L}{sup 0}

    Energy Technology Data Exchange (ETDEWEB)

    Pire, B. [CPHT, Ecole Polytechnique, CNRS, Palaiseau (France); Segond, M. [LPTHE, Universite Paris 6 and 7, CNRS, Paris (France); LPT, Universite Paris-Sud, CNRS, Orsay (France); Szymanowski, L. [CPHT, Ecole Polytechnique, CNRS, Palaiseau (France); SINS, Warsaw (Poland); Wallon, S. [LPT, Universite Paris-Sud, CNRS, Orsay (France)

    2008-11-15

    The exclusive process e{sup +}e{sup -}{yields}e{sup +}e{sup -}{rho}{sub L}{sup 0}{rho}{sub L}{sup 0} allows to study various dynamics and factorization properties of perturbative QCD. At moderate energy, we demonstrate how collinearQCD factorization emerges, involving either generalized distribution amplitudes (GDA) or transition distribution amplitudes (TDA). At higher energies, in the Regge limit of QCD, we show that it offers a promising probe of the BFKL resummation effects to be studied at ILC.

  11. RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

    International Nuclear Information System (INIS)

    Rousseau, Matthieu; Gaugler, Marie-Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Paris, François; Corre, Isabelle

    2011-01-01

    Highlights: ► We explore the role of RhoA in endothelial cell response to ionizing radiation. ► RhoA is rapidly activated by single high-dose of radiation. ► Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. ► Radiation-induced apoptosis does not require the RhoA/ROCK pathway. ► Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.

  12. Ameloblasts require active RhoA to generate normal dental enamel.

    Science.gov (United States)

    Xue, Hui; Li, Yong; Everett, Eric T; Ryan, Kathleen; Peng, Li; Porecha, Rakhee; Yan, Yan; Lucchese, Anna M; Kuehl, Melissa A; Pugach, Megan K; Bouchard, Jessica; Gibson, Carolyn W

    2013-08-01

    RhoA plays a fundamental role in regulation of the actin cytoskeleton, intercellular attachment, and cell proliferation. During amelogenesis, ameloblasts (which produce the enamel proteins) undergo dramatic cytoskeletal changes and the RhoA protein level is up-regulated. Transgenic mice were generated that express a dominant-negative RhoA transgene in ameloblasts using amelogenin gene-regulatory sequences. Transgenic and wild-type (WT) molar tooth germs were incubated with sodium fluoride (NaF) or sodium chloride (NaCl) in organ culture. Filamentous actin (F-actin) stained with phalloidin was elevated significantly in WT ameloblasts treated with NaF compared with WT ameloblasts treated with NaCl or with transgenic ameloblasts treated with NaF, thereby confirming a block in the RhoA/Rho-associated protein kinase (ROCK) pathway in the transgenic mice. Little difference in quantitative fluorescence (an estimation of fluorosis) was observed between WT and transgenic incisors from mice provided with drinking water containing NaF. We subsequently found reduced transgene expression in incisors compared with molars. Transgenic molar teeth had reduced amelogenin, E-cadherin, and Ki67 compared with WT molar teeth. Hypoplastic enamel in transgenic mice correlates with reduced expression of the enamel protein, amelogenin, and E-cadherin and cell proliferation are regulated by RhoA in other tissues. Together these findings reveal deficits in molar ameloblast function when RhoA activity is inhibited. © 2013 Eur J Oral Sci.

  13. Lifetime of rho meson in correlation with magnetic-dimensional reduction

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Mamiya [Nagoya University, Department of Physics, Nagoya (Japan); Matsuzaki, Shinya [Nagoya University, Department of Physics, Nagoya (Japan); Nagoya University, Institute for Advanced Research, Nagoya (Japan)

    2017-04-15

    It is naively expected that in a strong magnetic configuration, the Landau quantization ceases the neutral rho meson to decay to the charged pion pair, so the neutral rho meson will be long-lived. To closely access this naive observation, we explicitly compute the charged pion loop in the magnetic field at the one-loop level, to evaluate the magnetic dependence of the lifetime for the neutral rho meson as well as its mass. Due to the dimensional reduction induced by the magnetic field (violation of the Lorentz invariance), the polarization (spin s{sub z} = 0, ±1) modes of the rho meson, as well as the corresponding pole mass and width, are decomposed in a nontrivial manner compared to the vacuum case. To see the significance of the reduction effect, we simply take the lowest Landau level approximation to analyze the spin-dependent rho masses and widths. We find that the ''fate'' of the rho meson may be more complicated because of the magnetic-dimensional reduction: as the magnetic field increases, the rho width for the spin s{sub z} = 0 starts to develop, reaches a peak, then vanishes at the critical magnetic field to which the folklore refers. On the other side, the decay rates of the other rhos for s{sub z} = ±1 monotonically increase as the magnetic field develops. The correlation between the polarization dependence and the Landau level truncation is also addressed. (orig.)

  14. Basal and Activated Calcium Sensitization Mediated by RhoA/Rho Kinase Pathway in Rats with Genetic and Salt Hypertension

    Czech Academy of Sciences Publication Activity Database

    Behuliak, Michal; Bencze, Michal; Vaněčková, Ivana; Kuneš, Jaroslav; Zicha, Josef

    2017-01-01

    Roč. 2017, January (2017), č. článku 8029728. ISSN 2314-6133 R&D Projects: GA ČR(CZ) GP14-16225P; GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : calcium sensitization * RhoA/Rho kinase * fasudil * calcium influx * nifedipine * BAY K8644 Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery OBOR OECD: Cardiac and Cardiovascular systems Impact factor: 2.476, year: 2016

  15. Problems with rho R measurements: what are the ways out

    International Nuclear Information System (INIS)

    Pan, Y.L.; Larsen, J.T.

    1977-01-01

    An important scaling parameter or figure of merit in inertially-confined fusion is the maximum fuel rho R achieved by the target--rho is the density, and R the radius of the fuel. Every technique used, thus far, in laser-initiated-fusion-microexplosion experiments to obtain this data had major deficiencies. We examine critically the merits of the various possible methods of measuring fuel rho R and their ranges of applicability

  16. RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism

    International Nuclear Information System (INIS)

    Yamaki, Nao; Negishi, Manabu; Katoh, Hironori

    2007-01-01

    In normal epithelial cells, cell-matrix interaction is required for cell survival and proliferation, whereas disruption of this interaction causes epithelial cells to undergo apoptosis called anoikis. Here we show that the small GTPase RhoG plays an important role in the regulation of anoikis. HeLa cells are capable of anchorage-independent cell growth and acquire resistance to anoikis. We found that RNA interference-mediated knockdown of RhoG promoted anoikis in HeLa cells. Previous studies have shown that RhoG activates Rac1 and induces several cellular functions including promotion of cell migration through its effector ELMO and the ELMO-binding protein Dock180 that function as a Rac-specific guanine nucleotide exchange factor. However, RhoG-induced suppression of anoikis was independent of the ELMO- and Dock180-mediated activation of Rac1. On the other hand, the regulation of anoikis by RhoG required phosphatidylinositol 3-kinase (PI3K) activity, and constitutively active RhoG bound to the PI3K regulatory subunit p85α and induced the PI3K-dependent phosphorylation of Akt. Taken together, these results suggest that RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1

  17. Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

    Directory of Open Access Journals (Sweden)

    Chinestra Patrick

    2008-03-01

    Full Text Available Abstract Background The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings. Results After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L, three scFvs (A8, C1 and D11 were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2, it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence. Conclusion We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated

  18. Tentative of observation of the {rho}{sup +} {yields} {pi}{sup +} + {gamma} decay mode; Tentative de mise en evidence du mode de desintegration {rho}{sup +} {yields} {pi}{sup +} + {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Daudin, A.; Jabiol, M.A.; Kochowski, C.; Lewin, C.; Rogozinski, A. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Mongelli, S.; Romano, A.; Waloschek, P. [Istituto di Fisica dell' Universita, Bari (Italy)

    1964-07-01

    One of the purposes of the 1.6 GeV/c {pi}{sup +} p experiment, carried out in the 50 cm Saclay hydrogen bubble chamber, was to observe the {rho}{sup +} {yields} {pi}{sup +} {gamma} radiative decay mode in {pi}{sup +} p {yields} {pi}{sup +} p {gamma} interactions. A 6 mm thick lead plate, set at the outgoing part of the chamber, was used to convert {gamma} into e{sup +} e{sup -}. Among the {gamma} observed arising directly from the investigated interactions, no event originates from a {pi}{sup +} {gamma} compound in the region of {rho}{sup +}. This gives an upper limit of 2 per cent for the branching ratio ({rho}{sup +} {yields} {pi}{sup +} {gamma}) / ({rho}{sup +} {yields} {pi}{sup +} {gamma} + {rho}{sup +} {yields} {pi}{sup +} {pi}{sup 0}). (authors) [French] Une experience, dont l'un des buts etait de mettre en evidence le mode de desintegration radiatif du {rho}{sup +} en {pi}{sup +} {gamma} dans les interactions {pi}{sup +} p {yields} p {pi}{sup +} {gamma} a 1,6 GeV/c, a ete effectuee a l'aide de la chambre a bulles a hydrogene liquide de 50 cm de diametre de Saclay. Une plaque de plomb de 6 mm d'epaisseur, servant de convertisseur {gamma} {yields} e{sup +} e{sup -} a ete placee au sein du liquide a la sortie de la chambre. Parmi les y observes issus directement de l'interaction etudiee, aucun ne provient d'un complexe {pi}{sup +} {gamma} ayant la masse du {rho}{sup +}, ce qui fixe la limite superieure du rapport de branchement ({rho}{sup +} {yields} {pi}{sup +} {gamma}) / ({rho}{sup +} {yields} {pi}{sup +} {gamma} + {rho}{sup +} {yields} {pi}{sup +} {pi}{sup 0}) a 2 pour cent. (auteurs)

  19. Characterization of RhoC Expression in Benign and Malignant Breast Disease

    Science.gov (United States)

    Kleer, Celina G.; van Golen, Kenneth L.; Zhang, Yanhong; Wu, Zhi-Fen; Rubin, Mark A.; Merajver, Sofia D.

    2002-01-01

    The most important factor in predicting outcome in patients with early breast cancer is the stage of the disease. There is no robust marker capable of identifying invasive carcinomas that despite their small size have a high metastatic potential, and that would benefit from more aggressive treatment. RhoC-GTPase is a member of the Ras-superfamily and is involved in cell polarity and motility. We hypothesized that RhoC expression would be a good marker to identify breast cancer patients with high risk of developing metastases, and that it would be a prognostic marker useful in the clinic. We developed a specific anti-RhoC antibody and studied archival breast tissues that comprise a broad spectrum of breast disease. One hundred eighty-two specimens from 164 patients were used. Immunohistochemistry was performed on formalin-fixed tissues. Staining intensity was graded 0 to 3+ (0 to 1+ was considered negative and 2 to 3+ was considered positive). RhoC was not expressed in any of the normal, fibrocystic changes, atypical hyperplasia, or ductal carcinoma in situ, but was expressed in 36 of 118 invasive carcinomas and strongly correlated with tumor stage (P = 0.01). RhoC had high specificity (88%) in detecting invasive carcinomas with metastatic potential. Of the invasive carcinomas smaller than 1 cm, RhoC was highly specific in detecting tumors that developed metastases. RhoC expression was associated with negative progesterone receptor and HER-2/neu overexpression. We characterized RhoC expression in human breast tissues. RhoC is specifically expressed in invasive breast carcinomas capable of metastasizing, and it may be clinically useful in patients with tumors smaller than 1 cm to guide treatment. PMID:11839578

  20. Implications of Rho GTPase signaling in glioma cell invasion and tumor progression

    Directory of Open Access Journals (Sweden)

    Shannon Patricia Fortin Ensign

    2013-10-01

    Full Text Available Glioblastoma (GB is the most malignant of primary adult brain tumors, characterized by a highly locally-invasive cell population, as well as abundant proliferative cells, neoangiogenesis, and necrosis. Clinical intervention with chemotherapy or radiation may either promote or establish an environment for manifestation of invasive behavior. Understanding the molecular drivers of invasion in the context of glioma progression may be insightful in directing new treatments for patients with GB. Here, we review current knowledge on Rho family GTPases, their aberrant regulation in GB, and their effect on GB cell invasion and tumor progression. Rho GTPases are modulators of cell migration through effects on actin cytoskeleton rearrangement; in non-neoplastic tissue, expression and activation of Rho GTPases are normally under tight regulation. In GB, Rho GTPases are deregulated, often via hyperactivity or overexpression of their activators, Rho GEFs. Downstream effectors of Rho GTPases have been shown to promote invasiveness and, importantly, glioma cell survival. The study of aberrant Rho GTPase signaling in GB is thus an important investigation of cell invasion as well as treatment resistance and disease progression.

  1. Effects of aromatics, olefins and distillation temperatures (T50 & T90) on particle mass and number emissions from gasoline direct injection (GDI) vehicles

    International Nuclear Information System (INIS)

    Zhu, Rencheng; Hu, Jingnan; Bao, Xiaofeng; He, Liqiang; Zu, Lei

    2017-01-01

    Abstratct: Fuel quality is among the primary reasons for severe vehicle pollution. A limited understanding of the effects of gasoline properties on modern vehicle emissions is one obstacle for the establishment of stricter fuel standards in China. The goal of this study was to evaluate the effects of aromatic and olefin contents and T50 and T90 (defined as the 50%v and 90%v distillation temperatures) on tailpipe emissions from gasoline direct injection (GDI) vehicles compliant with China 4 standards. Both gaseous and particle emissions using different types of gasoline were measured. Changing aromatic and olefin contents had relatively small impacts on fuel consumption. Compared with olefins and T90, the regulated gaseous emissions were impacted more by aromatics and T50. Evident decreases of the particle mass (PM) and particle number (PN) emissions were noticed when the aromatic content and T90 decreased. Reducing the olefin content slightly decreased the PM emissions and increased the PN emissions. With decreasing T50, the PM emissions increased and the PN emissions slightly decreased. These results suggest that aromatic content and T90 should be decreased to reduce particle emissions from GDI vehicles. The information presented in this study provides some suggestions for how to improve gasoline quality in China. - Highlights: • Effect of aromatics, olefins, T50 and T90 on GDI vehicle emissions was investigated. • Aromatics and olefins had little impact on fuel consumption and CO 2 emissions. • Reducing the aromatic content and T90 significantly decreased PM and PN emissions. • Changing the olefin content and T50 had a minor impact on particle emissions. • Thresholds of aromatics and T90 should be tightened in future gasoline regulations.

  2. Implementation of Pollard Rho attack on elliptic curve cryptography over binary fields

    Science.gov (United States)

    Wienardo, Yuliawan, Fajar; Muchtadi-Alamsyah, Intan; Rahardjo, Budi

    2015-09-01

    Elliptic Curve Cryptography (ECC) is a public key cryptosystem with a security level determined by discrete logarithm problem called Elliptic Curve Discrete Logarithm Problem (ECDLP). John M. Pollard proposed an algorithm for discrete logarithm problem based on Monte Carlo method and known as Pollard Rho algorithm. The best current brute-force attack for ECC is Pollard Rho algorithm. In this research we implement modified Pollard Rho algorithm on ECC over GF (241). As the result, the runtime of Pollard Rho algorithm increases exponentially with the increase of the ECC key length. This work also presents the estimated runtime of Pollard Rho attack on ECC over longer bits.

  3. C3 rho-inhibitor for targeted pharmacological manipulation of osteoclast-like cells.

    Directory of Open Access Journals (Sweden)

    Andrea Tautzenberger

    Full Text Available The C3 toxins from Clostridium botulinum (C3bot and Clostridium limosum (C3lim as well as C3-derived fusion proteins are selectively taken up into the cytosol of monocytes/macrophages where the C3-catalyzed ADP-ribosylation of Rho results in inhibition of Rho-signalling and characteristic morphological changes. Since the fusion toxin C2IN-C3lim was efficiently taken up into and inhibited proliferation of murine macrophage-like RAW 264.7 cells, its effects on RAW 264.7-derived osteoclasts were investigated. C2IN-C3lim was taken up into differentiated osteoclasts and decreased their resorption activity. In undifferentiated RAW 264.7 cells, C2IN-C3lim-treatment significantly decreased their differentiation into osteoclasts as determined by counting the multi-nucleated, TRAP-positive cells. This inhibitory effect was concentration- and time-dependent and most efficient when C2IN-C3lim was applied in the early stage of osteoclast-formation. A single-dose application of C2IN-C3lim at day 0 and its subsequent removal at day 1 reduced the number of osteoclasts in a comparable manner while C2IN-C3lim-application at later time points did not reduce the number of osteoclasts to a comparable degree. Control experiments with an enzymatically inactive C3 protein revealed that the ADP-ribosylation of Rho was essential for the observed effects. In conclusion, the results indicate that Rho-activity is crucial during the early phase of osteoclast-differentiation. Other bone cell types such as pre-osteoblastic cells were not affected by C2IN-C3lim. Due to their cell-type selective and specific mode of action, C3 proteins and C3-fusions might be valuable tools for targeted pharmacological manipulation of osteoclast formation and activity, which could lead to development of novel therapeutic strategies against osteoclast-associated diseases.

  4. Inelastic photoproduction of ω and rho+-mesons

    International Nuclear Information System (INIS)

    Nelson, C.A. Jr.; May, E.N.; Abramson, J.; Andrews, D.E.; Harvey, J.; Lobkowicz, F.; Singer, M.N.; Thorndike, E.H.; Nordberg, M.E. Jr.

    1978-01-01

    We report measurements of inelastic photoproduction of ω and rho +- mesons from hydrogen and deuterium at incident photon energies in the range 7.5-10.5 GeV. For ωΔ and rho - Δ ++ production differential cross sections dsigma/dt' and spin density matrices are presented. For higher missing masses the cross sections dsigma/dM/sub X/ 2 and invariant structure functions F(x) are also given. The data are compared to a one-pion-exchange model. We conclude that pion exchange is dominant for inelastic ω photoproduction, but unimportant for rho +- during annealing, even though the resistively determined transport scattering time increased by a factor of 7.8 during annealing. Orbital depairing was found to follow a relation zeta = zeta 0 + αH 2 and to increase with annealing in a manner expected from the change in mean free path determined from measurements of H/sub cnu/

  5. Impact of higher n-butanol addition on combustion and performance of GDI engine in stoichiometric combustion

    International Nuclear Information System (INIS)

    Chen, Zheng; Yang, Feng; Xue, Shuo; Wu, Zhenkuo; Liu, Jingping

    2015-01-01

    Highlights: • Effects of 0–50% n-butanol addition on GDI engine are experimentally studied. • Higher n-butanol fractions increase combustion pressure and fasten burning rate. • Higher n-butanol fractions increase BSFC but improve BTE. • Higher n-butanol fractions enhance combustion stability but increase knock intensity. • Higher n-butanol fractions reduce exhaust temperature and NOx emissions. - Abstract: An experimental study was carried out on a turbocharged gasoline direct injection (GDI) engine fueled by n-butanol/gasoline blends. Effects of n-butanol percents (15%, 30%, and 50%) on combustion and performance of the engine operating on stoichiometric combustion condition were discussed and also compared with pure gasoline in this paper. The results indicate that n-butanol/gasoline blends increase combustion pressure and pressure rise rate, fasten burning rate, and shorten ignition delay and combustion duration, as compared to pure gasoline. Moreover, these trends are impacted more evidently with increased n-butanol fraction in the blends. In addition, higher n-butanol percent of gasoline blends increase combustion temperature but decrease the temperature in the later stage of expansion stroke, which contributes to the control of exhaust temperature at high-load. With regards to engine performance, higher n-butanol percent in the blends results in increased brake specific fuel consumption (BSFC) and higher brake thermal efficiency (BTE). However, higher n-butanol addition helps to improve combustion stability but shows slightly higher knock possibility in high-load. In that case, the knock trend could be weakened by retarding ignition timing. Moreover, higher n-butanol addition significantly decreases NOx emissions, but it increases CO emissions obviously.

  6. RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes

    DEFF Research Database (Denmark)

    Jackson, Ben; Peyrollier, Karine; Pedersen, Esben

    2011-01-01

    RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice with a keratino......RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice......-cell contacts. Furthermore we observed increased cell spreading due to impaired RhoA-ROCK (Rho-associated protein kinase)-MLC phosphatase-MLC-mediated cell contraction, independent of Rac1. Rho-inhibiting toxins further increased multinucleation of RhoA-null cells but had no significant effect on spreading......, suggesting that RhoB and RhoC have partially overlapping functions with RhoA. Loss of RhoA decreased directed cell migration in vitro caused by reduced migration speed and directional persistence. These defects were not related to the decreased cell contraction and were independent of ROCK, as ROCK...

  7. RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

    DEFF Research Database (Denmark)

    Jennings, Richard T; Strengert, Monika; Hayes, Patti

    2014-01-01

    Neutrophil responses are central to host protection and inflammation. Neutrophil activation follows a two-step process where priming amplifies responses to activating stimuli. Priming is essential for life span extension, chemotaxis and respiratory burst activity. Here we show that the cytoskeletal...... organizer RhoA suppresses neutrophil priming via formins. Premature granule exocytosis in Rho-deficient neutrophils activated numerous signaling pathways and amplified superoxide generation. Deletion of Rho altered front-to-back coordination by simultaneously increasing uropod elongation, leading edge...... neutrophils exacerbated LPS-mediated lung injury, deleting Rho in innate immune cells was highly protective in Influenza A virus infection. Hence, Rho is a key regulator of disease progression by maintaining neutrophil quiescence and suppressing hyperresponsiveness....

  8. Born order study of {gamma}{sup *}{gamma}{sup *} {yields} {rho}{rho} at very high energy

    Energy Technology Data Exchange (ETDEWEB)

    Pire, B. [Ecole Polytechnique, 91 - Palaiseau (France). Centre de Physique Theorique; Szymanowski, L. [Soltan Institute for Nuclear Studies, Warsaw (Poland); Liege Univ. (Belgium); Wallon, S. [Paris-11 Univ., Lab. de Physique Theorique, 91 - Orsay (France)

    2005-07-01

    We calculate the cross-section for the diffractive exclusive process {gamma}{sub L}{sup *}(Q{sub 1}{sup 2}){gamma}{sub L}{sup *}(Q{sub 2}{sup 2}) {yields} {rho}{sub L}{sup 0}{rho}{sub L}{sup 0}, in view of its study in the future high energy e{sup +}e{sup -} linear collider. The Born order approximation of the amplitude is completely calculable in the hard region Q{sub 1}{sup 2},Q{sub 2}{sup 2} >> {lambda}{sup 2}(QCD). The resulting cross-section is large enough for this process to be measurable with foreseen luminosity and energy, for Q{sub 1}{sup 2} and Q{sub 2}{sup 2} in the range of a few GeV{sup 2}. (authors)

  9. Binding and Translocation of Termination Factor Rho Studied at the Single-Molecule Level

    Science.gov (United States)

    Koslover, Daniel J.; Fazal, Furqan M.; Mooney, Rachel A.; Landick, Robert; Block, Steven M.

    2012-01-01

    Rho termination factor is an essential hexameric helicase responsible for terminating 20–50% of all mRNA synthesis in E. coli. We used single- molecule force spectroscopy to investigate Rho-RNA binding interactions at the Rho- utilization (rut) site of the ? tR1 terminator. Our results are consistent with Rho complexes adopting two states, one that binds 57 ±2 nucleotides of RNA across all six of the Rho primary binding sites, and another that binds 85 ±2 nucleotides at the six primary sites plus a single secondary site situated at the center of the hexamer. The single-molecule data serve to establish that Rho translocates 5′-to-3′ towards RNA polymerase (RNAP) by a tethered-tracking mechanism, looping out the intervening RNA between the rut site and RNAP. These findings lead to a general model for Rho binding and translocation, and establish a novel experimental approach that should facilitate additional single- molecule studies of RNA-binding proteins. PMID:22885804

  10. BAR domain proteins regulate Rho GTPase signaling.

    Science.gov (United States)

    Aspenström, Pontus

    2014-01-01

    BAR proteins comprise a heterogeneous group of multi-domain proteins with diverse biological functions. The common denominator is the Bin-Amphiphysin-Rvs (BAR) domain that not only confers targeting to lipid bilayers, but also provides scaffolding to mold lipid membranes into concave or convex surfaces. This function of BAR proteins is an important determinant in the dynamic reconstruction of membrane vesicles, as well as of the plasma membrane. Several BAR proteins function as linkers between cytoskeletal regulation and membrane dynamics. These links are provided by direct interactions between BAR proteins and actin-nucleation-promoting factors of the Wiskott-Aldrich syndrome protein family and the Diaphanous-related formins. The Rho GTPases are key factors for orchestration of this intricate interplay. This review describes how BAR proteins regulate the activity of Rho GTPases, as well as how Rho GTPases regulate the function of BAR proteins. This mutual collaboration is a central factor in the regulation of vital cellular processes, such as cell migration, cytokinesis, intracellular transport, endocytosis, and exocytosis.

  11. Problem-Solving Test: The Mechanism of Transcription Termination by the Rho Factor

    Science.gov (United States)

    Szeberenyi, Jozsef

    2012-01-01

    Transcription termination comes in two forms in "E. coli" cells. Rho-dependent termination requires the binding of a termination protein called Rho factor to the transcriptional machinery at the terminator region, whereas Rho-independent termination is achieved by conformational changes in the transcript itself. This article presents a test…

  12. T1rho mapping of entire femoral cartilage using depth- and angle-dependent analysis

    International Nuclear Information System (INIS)

    Nozaki, Taiki; Kaneko, Yasuhito; Yu, Hon J.; Yoshioka, Hiroshi; Kaneshiro, Kayleigh; Schwarzkopf, Ran; Hara, Takeshi

    2016-01-01

    To create and evaluate normalized T1rho profiles of the entire femoral cartilage in healthy subjects with three-dimensional (3D) angle- and depth-dependent analysis. T1rho images of the knee from 20 healthy volunteers were acquired on a 3.0-T unit. Cartilage segmentation of the entire femur was performed slice-by-slice by a board-certified radiologist. The T1rho depth/angle-dependent profile was investigated by partitioning cartilage into superficial and deep layers, and angular segmentation in increments of 4 over the length of segmented cartilage. Average T1rho values were calculated with normalized T1rho profiles. Surface maps and 3D graphs were created. T1rho profiles have regional and depth variations, with no significant magic angle effect. Average T1rho values in the superficial layer of the femoral cartilage were higher than those in the deep layer in most locations (p < 0.05). T1rho values in the deep layer of the weight-bearing portions of the medial and lateral condyles were lower than those of the corresponding non-weight-bearing portions (p < 0.05). Surface maps and 3D graphs demonstrated that cartilage T1rho values were not homogeneous over the entire femur. Normalized T1rho profiles from the entire femoral cartilage will be useful for diagnosing local or early T1rho abnormalities and osteoarthritis in clinical applications. (orig.)

  13. T1rho mapping of entire femoral cartilage using depth- and angle-dependent analysis

    Energy Technology Data Exchange (ETDEWEB)

    Nozaki, Taiki; Kaneko, Yasuhito; Yu, Hon J.; Yoshioka, Hiroshi [University of California Irvine, Department of Radiological Sciences, Orange, CA (United States); Kaneshiro, Kayleigh [University of California Irvine, School of Medicine, Irvine, CA (United States); Schwarzkopf, Ran [University of California Irvine, Department of Orthopedic Surgery, Irvine, CA (United States); Hara, Takeshi [Gifu University Graduate School of Medicine, Department of Intelligent Image Information, Division of Regeneration and Advanced Medical Sciences, Gifu (Japan)

    2016-06-15

    To create and evaluate normalized T1rho profiles of the entire femoral cartilage in healthy subjects with three-dimensional (3D) angle- and depth-dependent analysis. T1rho images of the knee from 20 healthy volunteers were acquired on a 3.0-T unit. Cartilage segmentation of the entire femur was performed slice-by-slice by a board-certified radiologist. The T1rho depth/angle-dependent profile was investigated by partitioning cartilage into superficial and deep layers, and angular segmentation in increments of 4 over the length of segmented cartilage. Average T1rho values were calculated with normalized T1rho profiles. Surface maps and 3D graphs were created. T1rho profiles have regional and depth variations, with no significant magic angle effect. Average T1rho values in the superficial layer of the femoral cartilage were higher than those in the deep layer in most locations (p < 0.05). T1rho values in the deep layer of the weight-bearing portions of the medial and lateral condyles were lower than those of the corresponding non-weight-bearing portions (p < 0.05). Surface maps and 3D graphs demonstrated that cartilage T1rho values were not homogeneous over the entire femur. Normalized T1rho profiles from the entire femoral cartilage will be useful for diagnosing local or early T1rho abnormalities and osteoarthritis in clinical applications. (orig.)

  14. Dipole moments of the rho meson

    International Nuclear Information System (INIS)

    Hecht, M.B.; McKellar, B.H.P.

    1997-04-01

    The electric and magnetic dipole moments (EDM) of the rho meson are calculated using the propagators and vertices derived from the quantum chromodynamics Dyson-Schwinger equations. Results obtained from using the Bethe-Salpeter amplitude studied by Chappell, Mitchell et. al., and Pichowsky and Lee, are compared. The rho meson EDM is generated through the inclusion of a quark electric dipole moment, which is left as a free variable. These results are compared to the perturbative results to obtain a measure of the effects of quark interactions and confinement. The two dipole moments are also calculated using the phenomenological MIT bag model to provide a further basis for comparison

  15. Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation

    Science.gov (United States)

    Mita, Mitsuo; Tanaka, Hitoshi; Yanagihara, Hayato; Nakagawa, Jun-ichi; Hishinuma, Shigeru; Sutherland, Cindy; Walsh, Michael P.; Shoji, Masaru

    2013-01-01

    Rho-associated kinase (ROK) activation plays an important role in K+-induced contraction of rat caudal arterial smooth muscle (Mita et al., Biochem J. 2002; 364: 431–40). The present study investigated a potential role for tyrosine kinase activity in K+-induced RhoA activation and contraction. The non-selective tyrosine kinase inhibitor genistein, but not the src family tyrosine kinase inhibitor PP2, inhibited K+-induced sustained contraction (IC50 = 11.3 ± 2.4 µM). Genistein (10 µM) inhibited the K+-induced increase in myosin light chain (LC20) phosphorylation without affecting the Ca2+ transient. The tyrosine phosphatase inhibitor vanadate induced contraction that was reversed by genistein (IC50 = 6.5 ± 2.3 µM) and the ROK inhibitor Y-27632 (IC50 = 0.27 ± 0.04 µM). Vanadate also increased LC20 phosphorylation in a genistein- and Y-27632-dependent manner. K+ stimulation induced translocation of RhoA to the membrane, which was inhibited by genistein. Phosphorylation of MYPT1 (myosin-targeting subunit of myosin light chain phosphatase) was significantly increased at Thr855 and Thr697 by K+ stimulation in a genistein- and Y-27632-sensitive manner. Finally, K+ stimulation induced genistein-sensitive tyrosine phosphorylation of proteins of ∼55, 70 and 113 kDa. We conclude that a genistein-sensitive tyrosine kinase, activated by the membrane depolarization-induced increase in [Ca2+]i, is involved in the RhoA/ROK activation and sustained contraction induced by K+. Ca2+ sensitization, myosin light chain phosphatase, RhoA, Rho-associated kinase, tyrosine kinase PMID:24133693

  16. Enhanced flux pinning by BaZrO3 and (Gd,y)2O3 nano-structures in metal organic chemical vapor deposited GdYBCO high temperature superconductor tapes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y [SuperPower Incorporated, Schenectady, New York; Selvamanickam, V. [SuperPower Incorporated, Schenectady, New York; Paranthaman, Mariappan Parans [ORNL; Cantoni, Claudia [ORNL; Aytug, Tolga [ORNL; Goyal, Amit [ORNL; Lee, Dominic F [ORNL; Specht, Eliot D [ORNL; Zuev, Yuri L [ORNL; Zhang, Yifei [ORNL

    2009-01-01

    We have formed BaZrO3 nano-columns and (Gd,Y)2O3 nano-precipitates in reel-to-reel MOCVD processed (Gd,Y)Ba2Cu3O7-x coated conductors and increased the critical currents (Ic) of the conductors in applied magnetic fields to remarkable levels. A (Gd,Y)Ba2Cu3O7-x tape of 1m length with 6.5% Zr-additions and 30% composition rich in both Gd and Y showed Ic values of 813 A/cm-width at (self-field, 77K) and above 186 A/cm-width at (1T, 77K). The strongly enhanced flux pinning over a wide range of magnetic field orientations can be attributed to the bidirectionally aligned defect structures of BaZrO3 and (Gd,Y)2O3 created by optimized MOCVD conditions.

  17. Parameter Optimization on the Uniflow Scavenging System of an OP2S-GDI Engine Based on Indicated Mean Effective Pressure (IMEP

    Directory of Open Access Journals (Sweden)

    Fu-Kang Ma

    2017-03-01

    Full Text Available In this paper, an opposed-piston two-stroke (OP2S gasoline direct injection (GDI engine is introduced and its working principles and scavenging process were analyzed. An optimization function was established to optimize the scavenging system parameters, include intake port height, exhaust port height, intake port circumference ratio, the exhaust port circumference ratio and opposed-piston motion phase difference. The effect of the port height on the effective compression ratio and effective expansion ratio were considered, and indicated mean effective pressure (IMEP was employed as the optimization objective instead of scavenging efficiency. Orthogonal experiments were employed to reduce the calculation work. The effect of the scavenging parameters on delivery ratio, trapping ratio, scavenging efficiency and indicated thermal efficiency were calculated, and the best parameters were also obtained by the optimization function. The results show that IMEP can be used as the optimization objective in the uniflow scavenging system; intake port height is the main factor to the delivery ratio, while exhaust port height is the main to engine trapping ratio, scavenging efficiency and indicated thermal efficiency; exhaust port height is the most important factor to effect the gas exchange process of OP2S-GDI engine.

  18. The interdependence of the Rho GTPases and apicobasal cell polarity.

    Science.gov (United States)

    Mack, Natalie Ann; Georgiou, Marios

    2014-01-01

    Signaling via the Rho GTPases provides crucial regulation of numerous cell polarization events, including apicobasal (AB) polarity, polarized cell migration, polarized cell division and neuronal polarity. Here we review the relationships between the Rho family GTPases and epithelial AB polarization events, focusing on the 3 best-characterized members: Rho, Rac and Cdc42. We discuss a multitude of processes that are important for AB polarization, including lumen formation, apical membrane specification, cell-cell junction assembly and maintenance, as well as tissue polarity. Our discussions aim to highlight the immensely complex regulatory mechanisms that encompass Rho GTPase signaling during AB polarization. More specifically, in this review we discuss several emerging common themes, that include: 1) the need for Rho GTPase activities to be carefully balanced in both a spatial and temporal manner through a multitude of mechanisms; 2) the existence of signaling feedback loops and crosstalk to create robust cellular responses; and 3) the frequent multifunctionality that exists among AB polarity regulators. Regarding this latter theme, we provide further discussion of the potential plasticity of the cell polarity machinery and as a result the possible implications for human disease.

  19. Convergent use of RhoGAP toxins by eukaryotic parasites and bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    Dominique Colinet

    2007-12-01

    Full Text Available Inactivation of host Rho GTPases is a widespread strategy employed by bacterial pathogens to manipulate mammalian cellular functions and avoid immune defenses. Some bacterial toxins mimic eukaryotic Rho GTPase-activating proteins (GAPs to inactivate mammalian GTPases, probably as a result of evolutionary convergence. An intriguing question remains whether eukaryotic pathogens or parasites may use endogenous GAPs as immune-suppressive toxins to target the same key genes as bacterial pathogens. Interestingly, a RhoGAP domain-containing protein, LbGAP, was recently characterized from the parasitoid wasp Leptopilina boulardi, and shown to protect parasitoid eggs from the immune response of Drosophila host larvae. We demonstrate here that LbGAP has structural characteristics of eukaryotic RhoGAPs but that it acts similarly to bacterial RhoGAP toxins in mammals. First, we show by immunocytochemistry that LbGAP enters Drosophila immune cells, plasmatocytes and lamellocytes, and that morphological changes in lamellocytes are correlated with the quantity of LbGAP they contain. Demonstration that LbGAP displays a GAP activity and specifically interacts with the active, GTP-bound form of the two Drosophila Rho GTPases Rac1 and Rac2, both required for successful encapsulation of Leptopilina eggs, was then achieved using biochemical tests, yeast two-hybrid analysis, and GST pull-down assays. In addition, we show that the overall structure of LbGAP is similar to that of eukaryotic RhoGAP domains, and we identify distinct residues involved in its interaction with Rac GTPases. Altogether, these results show that eukaryotic parasites can use endogenous RhoGAPs as virulence factors and that despite their differences in sequence and structure, eukaryotic and bacterial RhoGAP toxins are similarly used to target the same immune pathways in insects and mammals.

  20. Measurement of Branching Fractions and CP-violating Charge Asymmetries in B sup + -> rho sup +pi sup 0 and B sup + -> rho sup 0 pi sup + decays, and search for B sup 0 -> rho sup 0 pi sup 0

    CERN Document Server

    Yu, Z

    2003-01-01

    The present preliminary measurements of branching fractions and CP-violating charge asymmetries in B-meson decays to rho pi. The data sample comprises 89 million UPSILON(4S) -> B(bar B) decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factor at SLAC. They find the charge-averaged branching fractions BETA(B sup + -> rho sup +pi sup 0) = (11.0 +- 1.9(stat.) +- 1.9(syst.)) x 10 sup - sup 6 and BETA(B sup + -> rho sup 0 pi sup +) = (9.3 +- 1.0(stat.) +- 0.8(syst.)) x 10 sup - sup 6; they set a 90% confidence-level upper limit of BETA(B sup 0 -> rho sup 0 pi sup 0) < 2.5 x 10 sup - sup 6. They measure the CP-violating charge asymmetries A sub C sub P suprho sup + suppi sup 0 = 0.23 +- 0.16(stat.) +- 0.06(syst.) and A sub C sub P suprho sup 0 suppi sup + = -0.17 +- 0.11(stat.) +- 0.02(syst.).

  1. RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.

    Directory of Open Access Journals (Sweden)

    Enric Mocholí

    Full Text Available Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.

  2. Differential effects of Rho-kinase inhibitor and angiotensin II type-1 receptor antagonist on the vascular function in hypertensive rats induced by chronic l-NAME treatment

    Directory of Open Access Journals (Sweden)

    Bainian Chen

    2012-10-01

    Full Text Available Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension. We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the NG-nitro-l-arginine methyl ester (l-NAME treated rat, as well as to compare the differential effects of fasudil and angiotensin II receptor antagonist valsartan on vascular function. In the present study, both valsartan and fasudil exerted antihypertensive action on the l-NAME-treated rats, while only valsartan attenuated the cardiac hypertrophy. Treatment with valsartan showed improvement on vascular reactivity to norepinephrine, KCl and CaCl2, whereas fasudil therapy showed little effect on vasoconstriction. Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy. The increased expression of RhoA and Rho-kinase (ROCK in the vasculature was corrected well to normal level by either valsartan or fasudil administration, which seemed to be at least partially responsible for the beneficial effect of the drug infusion. These findings suggest that the angiotensin II receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor, whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin II receptor.

  3. Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

    International Nuclear Information System (INIS)

    Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen; Zhang, Yu; Zhuo, Zhi Zheng; Zhao, Guiming

    2017-01-01

    To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver

  4. Accurate and reproducible measurements of RhoA activation in small samples of primary cells.

    Science.gov (United States)

    Nini, Lylia; Dagnino, Lina

    2010-03-01

    Rho GTPase activation is essential in a wide variety of cellular processes. Measurement of Rho GTPase activation is difficult with limited material, such as tissues or primary cells that exhibit stringent culture requirements for growth and survival. We defined parameters to accurately and reproducibly measure RhoA activation (i.e., RhoA-GTP) in cultured primary keratinocytes in response to serum and growth factor stimulation using enzyme-linked immunosorbent assay (ELISA)-based G-LISA assays. We also established conditions that minimize RhoA-GTP in unstimulated cells without affecting viability, allowing accurate measurements of RhoA activation on stimulation or induction of exogenous GTPase expression. Copyright 2009 Elsevier Inc. All rights reserved.

  5. A solution to the rho-π puzzle: Spontaneously broken symmetries of the quark model

    International Nuclear Information System (INIS)

    Caldi, D.G.; Pagels, H.

    1976-01-01

    This article proposes a solution to the long-standing rho-π puzzle: How can the rho and π be members of a quark model U(6) 36 and the π be a Nambu-Goldstone boson satisfying partial conservation of the axial-vector current (PCAC) Our solution to the puzzle requires a revision of conventional concepts regarding the vector mesons rho, ω, K*, and phi. Just as the π is a Goldstone state, a collective excitation of the Nambu--Jona-Lasinio type, transforming as a member of the (3, 3) + (3, 3) representation of the chiral SU(3) x SU(3) group, so also the rho transforms like (3, 3) + (3, 3) and is also a collective state, a ''dormant'' Goldstone boson that is a true Goldstone boson in the static chiral U(6) x U(6) limit. The static chiral U(6) x U(6) is to be spontaneously broken to static U(6) in the vacuum. Relativisitc effects provide for U(6) breaking and a massive rho. This viewpoint has many consequences. Vector-meson dominance is a consequence of spontaneously broken chiral symmetry: the mechanism that couples the axial-vector current to the π couples the vector current to the rho. The transition rate is calculated as γ/sub rho/ -1 = f/sub pi//m/sub rho/ in rough agreement with experiment. This picture requires soft rho's to decouple. The chiral partner of the rho is not the A 1 but the B (1235). The experimental absence of the A 1 is no longer a theoretical embarrassment in this scheme. As the analog of PCAC for the pion we establish a tensor-field identity for the rho meson in which the rho is interpreted as a dormant Goldstone state. The decays delta → eta + π, B → ω + π, epsilon → 2π are estimated and are found to be in agreement with the observed rates. A static U(6) x U(6) generalization of the Σ model is presented with the π, rho, sigma, B in the (6, 6) + (6, 6) representation. The rho emerges as a dormant Goldstone boson in this model

  6. Effect of external hot EGR dilution on combustion, performance and particulate emissions of a GDI engine

    International Nuclear Information System (INIS)

    Xie, Fangxi; Hong, Wei; Su, Yan; Zhang, Miaomiao; Jiang, Beiping

    2017-01-01

    Highlights: • Effect of hot EGR on combustion and PN emission is investigated on a GDI engine. • Appropriate addition of hot EGR can reduce fuel consumption, NO_x and PN emission. • Relationship between BSFC and emissions of hot EGR is better than cooled EGR. • Condition with low-medium speeds and medium loads are more suitable for hot EGR. - Abstract: In this paper, an experimental investigation about the influence of hot EGR addition on the engine combustion, performance and particulate number emission was conducted at a spark-ignition gasoline direct injection (GDI) engine. Meanwhile, the different effects between cooled and hot EGR addition methods were compared and the variations of fuel consumption and particle number emissions under six engine operating conditions with different speeds and loads were analyzed. The research result indicated that increasing hot EGR ratio properly with adjustment of ignition timing could effectively improve the relationship among brake-specific fuel consumption (BSFC), NO_x and particle number emissions. When hot EGR ratio increased to 20%, not only BSFC but also the NO_x and particle number emissions were reduced, which were about 7%, 87% and 36% respectively. Compared with cooled EGR, the flame development and propagation speeds were accelerated, and cycle-by-cycle combustion variation decreased with hot EGR. Meanwhile, using hot EGR made the engine realize a better relationship among fuel consumption, NO_x and particle number emissions. The biggest improvements of BSFC, NO_x and particle number emissions were obtained at low-medium speed and medium load engine conditions by hot EGR addition method. While engine speed increased and load decreased, the improvement of engine fuel consumption and emission reduced with hot EGR method.

  7. Involvement of rho-gtpases in fibroblast adhesion and fibronectine fibrillogenesis under stretch

    Science.gov (United States)

    Guignandon, A.; Lambert, C.; Rattner, A.; Servotte, S.; Lapiere, C.; Nusgens, B.; Vico, L.

    The Rho family small GTPases play a crucial role in mediating cellular adaptation to mechanical stimulation (MS), and possibly to microgravity (μg), through effects on the cytoskeleton and cell adhesion which is, in turn, mainly regulated by fibronectin fibrillogenesis (FnF). It remains unclear how mechanical stimulation is transduced to the Rho signaling pathways and how it impacts on fibronectin (fbn) fibrillogenesis (FnF). μg (2 days, mission STS-095) led to de-adhesion of fibroblasts and modification of the underlying extracellular matrix. To determine whether GTPases modulated FnF, we generated stable cell lines expressing high level of activated RhoA and Rac1 (QL) as compared to wild type (WI26-WT). After MS application [8% deformation, 1Hz, 15 min., 3 times/day for 1-2 days], we quantified focal adhesion (vinculin, paxillin, FAKY397), f-actin stress fibers (Sf) and FnF with home-developed softwares. We reported that after MS, Sf are more rapidly (30min) formed under the nucleus in Wi26-WT (+100%) and Rac1 (+200%) than in RhoA (+20%). Vinculin & paxillin were only restricted to the cell edge in static conditions and homogeneously distributed after MS in WT and Rac1. The relative area of contacts (vinculin & paxillin) was more dramatically enhanced by MS in Rac1 (+80%) than in WT (+40%) and RhoA (+25%) indicating that new focal contacts are formed under MS and supported the presence of Sf. MS Activation of FAK (FAKY397) was clear in WT and Rac1 and reduced in RhoA. FnF was restricted to cell-cell contacts zone without any change in the relative area of fbn after a 2-days MS. However we found more numerous spots of fbn at the cell center in Rac1 as compared with RhoA & WT suggesting that these fibrillar contacts will grow upon maturation and modulate FnF. The results indicate that MS induces formation of Sf and focal adhesions and enhances FF. RhoA has been shown to induce the formation of Sf and focal adhesions, and Rac1 activation decreases Rho activity in

  8. Rac and Rho GTPases in cancer cell motility control

    Directory of Open Access Journals (Sweden)

    Parri Matteo

    2010-09-01

    Full Text Available Abstract Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. Cells exhibit three distinct modes of migration when invading the 3 D environment. Collective motility leads to movement of cohorts of cells which maintain the adherens junctions and move by photolytic degradation of matrix barriers. Single cell mesenchymal-type movement is characterized by an elongated cellular shape and again requires extracellular proteolysis and integrin engagement. In addition it depends on Rac1-mediated cell polarization and lamellipodia formation. Conversely, in amoeboid movement cells have a rounded morphology, the movement is independent from proteases but requires high Rho GTPase to drive elevated levels of actomyosin contractility. These two modes of cell movement are interconvertible and several moving cells, including tumor cells, show an high degree of plasticity in motility styles shifting ad hoc between mesenchymal or amoeboid movements. This review will focus on the role of Rac and Rho small GTPases in cell motility and in the complex relationship driving the reciprocal control between Rac and Rho granting for the opportunistic motile behaviour of aggressive cancer cells. In addition we analyse the role of these GTPases in cancer progression and metastatic dissemination.

  9. Peptide substrates for Rho-associated kinase 2 (Rho-kinase 2/ROCK2.

    Directory of Open Access Journals (Sweden)

    Jeong-Hun Kang

    Full Text Available Peptide substrates sensitive for a certain protein kinase could be important for new-drug development and to understand the mechanism of diseases. Rho-associated kinase (Rho-kinase/ROCK is a serine/threonine kinase, and plays an important part in cardiovascular disease, migration and invasion of tumor cells, and in neurological disorders. The purpose of this study was to find substrates with high affinity and sensitivity for ROCK2. We synthesized 136 peptide substrates from protein substrates for ROCK2 with different lengths and charged peptides. Incorporation of (32P [counts per minute (CPM] for each peptide substrate was determined by the radiolabel assay using [γ-(32P]ATP. When the top five peptide substrates showing high CPMs (R4, R22, R133, R134, and R135 were phosphorylated by other enzymes (PKA, PKCα, and ERK1, R22, R133, and R135 displayed the highest CPM level for ROCK2 compared with other enzymes, whereas R4 and R134 showed similar CPM levels for ROCK2 and PKCα. We hypothesize that R22, R133, and R135 can be useful peptide substrates for ROCK2.

  10. ER stress in retinal degeneration in S334ter Rho rats.

    Directory of Open Access Journals (Sweden)

    Vishal M Shinde

    Full Text Available The S334ter rhodopsin (Rho rat (line 4 bears the rhodopsin gene with an early termination codon at residue 334 that is a model for several such mutations found in human patients with autosomal dominant retinitis pigmentosa (ADRP. The Unfolded Protein Response (UPR is implicated in the pathophysiology of several retinal disorders including ADRP in P23H Rho rats. The aim of this study was to examine the onset of UPR gene expression in S334ter Rho retinas to determine if UPR is activated in ADRP animal models and to investigate how the activation of UPR molecules leads to the final demise of S334ter Rho photoreceptors. RT-PCR was performed to evaluate the gene expression profiles for the P10, P12, P15, and P21 stages of the development and progression of ADRP in S334ter Rho photoreceptors. We determined that during the P12-P15 period, ER stress-related genes are strongly upregulated in transgenic retinas, resulting in the activation of the UPR that was confirmed using western blot analysis and RT-PCR. The activation of UPR was associated with the increased expression of JNK, Bik, Bim, Bid, Noxa, and Puma genes and cleavage of caspase-12 that together with activated calpains presumably compromise the integrity of the mitochondrial MPTP, leading to the release of pro-apoptotic AIF1 into the cytosol of S334ter Rho photoreceptor cells. Therefore, two major cross-talking pathways, the UPR and mitochondrial MPTP occur in S334ter-4 Rho retina concomitantly and eventually promote the death of the photoreceptor cells.

  11. Table of charged particle energies versus magnetic field strength x orbit radius (B{rho}) for A = 1 to 7 (100< (B{rho}) < 1200 kG.cm); Table des energies des particules chargees en fonction de la rigidite magnetique (B{rho}) pour A = 1 a 7 (100< (B{rho}) < 1200 kG.cm)

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, L. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1969-07-01

    A table of charged particle energies versus magnetic field strength x orbit radius (B{sub {rho}}) is presented. Particles p, d, t, {sup 3}He{sup ++}, {sup 4}He{sup +}, {sup 4}He{sup ++}, {sup 6}Li{sup +}, {sup 6}Li{sup ++}, {sup 6}Li{sup +++}, {sup 7}Li{sup +}, {sup 7}Li{sup ++}, {sup 7}Li{sup +++}. Values of B{sub {rho}}: 100 to 1200 kG.cm by steps of 0.5 kG.cm. Values of energies are given in keV. (author) [French] Nous presentons une table des energies de protons, deutons, tritons, {sup 3}He{sup ++}, {sup 4}He{sup +}, {sup 4}He{sup ++}, {sup 6}Li{sup +}, {sup 6}Li{sup ++}, {sup 6}Li{sup +++}, {sup 7}Li{sup +}, {sup 7}Li{sup ++}, {sup 7}Li{sup +++} en fonction de leur rigidite magnetique (B{sub {rho}}). Les valeurs de B{sub {rho}} sont comprises entre 100 et 1200 kG.cm par pas de 0.5 kG.cm. Les valeurs des energies sont donnees en keV. (auteur)

  12. Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B▿ †

    Science.gov (United States)

    Gautam, Poonam; Shankar, Jata; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Gade, Wasudev Namdeo; Basir, Seemi Farhat; Sarma, Puranam Usha

    2008-01-01

    Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections, including invasive aspergillosis. It has been our aim to understand the molecular targets of AMB in Aspergillus fumigatus by genomic and proteomic approaches. In transcriptomic analysis, a total of 295 genes were found to be differentially expressed (165 upregulated and 130 downregulated), including many involving the ergosterol pathway, cell stress proteins, cell wall proteins, transport proteins, and hypothetical proteins. Proteomic profiles of A. fumigatus alone or A. fumigatus treated with AMB showed differential expression levels for 85 proteins (76 upregulated and 9 downregulated). Forty-eight of them were identified with high confidence and belonged to the above-mentioned categories. Differential expression levels for Rho-GDP dissociation inhibitor (Rho-GDI), secretory-pathway GDI, clathrin, Sec 31 (a subunit of the exocyst complex), and RAB GTPase Ypt51 in response to an antifungal drug are reported here for the first time and may represent a specific response of A. fumigatus to AMB. The expression of some of these genes was validated by real-time reverse transcription-PCR. The AMB responsive genes/proteins observed to be differentially expressed in A. fumigatus may be further explored for novel drug development. PMID:18838595

  13. Proteomic and transcriptomic analysis of Aspergillus fumigatus on exposure to amphotericin B.

    Science.gov (United States)

    Gautam, Poonam; Shankar, Jata; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Gade, Wasudev Namdeo; Basir, Seemi Farhat; Sarma, Puranam Usha

    2008-12-01

    Amphotericin B (AMB) is the most widely used polyene antifungal drug for the treatment of systemic fungal infections, including invasive aspergillosis. It has been our aim to understand the molecular targets of AMB in Aspergillus fumigatus by genomic and proteomic approaches. In transcriptomic analysis, a total of 295 genes were found to be differentially expressed (165 upregulated and 130 downregulated), including many involving the ergosterol pathway, cell stress proteins, cell wall proteins, transport proteins, and hypothetical proteins. Proteomic profiles of A. fumigatus alone or A. fumigatus treated with AMB showed differential expression levels for 85 proteins (76 upregulated and 9 downregulated). Forty-eight of them were identified with high confidence and belonged to the above-mentioned categories. Differential expression levels for Rho-GDP dissociation inhibitor (Rho-GDI), secretory-pathway GDI, clathrin, Sec 31 (a subunit of the exocyst complex), and RAB GTPase Ypt51 in response to an antifungal drug are reported here for the first time and may represent a specific response of A. fumigatus to AMB. The expression of some of these genes was validated by real-time reverse transcription-PCR. The AMB responsive genes/proteins observed to be differentially expressed in A. fumigatus may be further explored for novel drug development.

  14. Study of the decay B0(barB0) --> rho+rho-, and constraints on the CKM angle α

    International Nuclear Information System (INIS)

    Aubert, B.; Babar Collaboration

    2004-01-01

    Using a data sample of 89 million Υ(4S)-->BBbar decays collected with the BaBar detector at the PEP-II asymmetric B Factory at SLAC, we measure the B 0 (barB 0 )-->rho + rho - branching fraction as (30+-4 (stat)+-5(syst)) x 10 -6 and a longitudinal polarization fraction of f L 0.99+-0.03(stat) +0.04 ) -0.03 (syst). We measure the time-dependent-asymmetry parameters of the longitudinally polarized component of this decay as C L = -0.17+-0.27(stat)+-0.14 (syst) and S L -0.42+-0.42(stat)+-0.14(syst). We present constraints on the CKM angle α

  15. Rho GTPasas como blancos terapéuticos relevantes en cáncer y otras enfermedades humanas Rho GTPases as therapeutic targets in cancer and other human diseases

    Directory of Open Access Journals (Sweden)

    Pablo Lorenzano Menna

    2010-12-01

    Full Text Available Las Rho GTPasas son una familia de proteínas clave en la transmisión de señales provenientes del exterior celular hacia efectores intracelulares tanto citoplasmáticos como nucleares. En los últimos año ha habido un desarrollo vertiginoso de múltiples herramientas genéticas y farmacológicas, lo que ha permitido establecer de manera mucho más precisa las funciones específicas de estas proteínas. El objetivo de la presente revisión es hacer foco en las múltiples funciones celulares reguladas por las Rho GTPasas, describiendo en detalle el mecanismo molecular involucrado. Se discute además la participación de estas proteínas en diversas enfermedades humanas haciendo énfasis en su vinculación con el cáncer. Por último, se hace una actualización detallada sobre las estrategias terapéuticas en experimentación que tienen a las Rho GTPasas como blancos moleculares.Rho GTPases are a key protein family controlling the transduction of external signals to cytoplasmatic and nuclear effectors. In the last few years, the development of genetic and pharmacological tools has allowed a more precise definition of the specific roles of Rho GTPases. The aim of this review is to describe the cellular functions regulated by these proteins with focus on the molecular mechanism involved. We also address the role of Rho GTPases in the development of different human diseases such as cancer. Finally, we describe different experimental therapeutic strategies with Rho GTPases as molecular targets.

  16. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2006-01-01

    Rho GTPases are molecular switches that fluctuate between on and off states. When active, these proteins function to remodel the actin cytoskeleton by interacting with a number of downstream effector molecules...

  17. Rational Design of Rho Protein Inhibitors

    National Research Council Canada - National Science Library

    Rojas, Rafael J

    2005-01-01

    Rho GTPases are molecular switches that fluctuate between on and off states. When active, these proteins function to remodel the actin cytoskeleton by interacting with a number of downstream effector molecules...

  18. Critique of Dilley's N/D generation of the rho resonance

    International Nuclear Information System (INIS)

    Tryon, E.P.

    1977-01-01

    Rigorous sum rules for negative moments of the discontinuity across the left-hand cut of the ππ P wave are derived and analyzed. A model by Dilley wherein the rho resonance emerges from elastic N/D equations is shown to be severely inconsistent with these sum rules. Dilley's method for selecting the input left cut is analyzed and shown to be strongly biased in favor of generating a rho. Because of this bias, together with the aforementioned violation of sum rules, Dilley's model does not comprise evidence that the rho is generated by forces in the ππ channel. Numerous successes of the quark model suggest otherwise

  19. Rotation in USco and rho Oph with K2

    Science.gov (United States)

    Rebull, Luisa; Stauffer, John; K2 Clusters Team

    2018-01-01

    K2 observed Upper Scorpius and rho Oph as part of their Campaign 2 in 2014. At ~8 and ~1 Myr respectively, the stars in Upper Sco and rho Oph exhibit greater diversity of light curve shapes than are found in older clusters observed with K2 such as Pleiades or Praesepe. Nonetheless, we are able to derive rotation periods for 85% (971/1136) of the USco members and 80% (71/88) of the rho Oph members. About 25% of the periodic stars have evidence for multiple periods. These light curves sample smaller amplitudes to lower masses and with a far better cadence, than has even been probed before. We can compare USco with similar stars in Praesepe (~700 Myr) and the Pleiades (~125 Myr), all with K2 light curves.

  20. Rnd3 induces stress fibres in endothelial cells through RhoB

    Directory of Open Access Journals (Sweden)

    Undine Gottesbühren

    2012-12-01

    Rnd proteins are atypical Rho family proteins that do not hydrolyse GTP and are instead regulated by expression levels and post-translational modifications. Rnd1 and Rnd3/RhoE induce loss of actin stress fibres and cell rounding in multiple cell types, whereas responses to Rnd2 are more variable. Here we report the responses of endothelial cells to Rnd proteins. Rnd3 induces a very transient decrease in stress fibres but subsequently stimulates a strong increase in stress fibres, in contrast to the reduction observed in other cell types. Rnd2 also increases stress fibres whereas Rnd1 induces a loss of stress fibres and weakening of cell–cell junctions. Rnd3 does not act through any of its known signalling partners and does not need to associate with membranes to increase stress fibres. Instead, it acts by increasing RhoB expression, which is then required for Rnd3-induced stress fibre assembly. Rnd2 also increases RhoB levels. These data indicate that the cytoskeletal response to Rnd3 expression is dependent on cell type and context, and identify regulation of RhoB as a new mechanism for Rnd proteins to affect the actin cytoskeleton.

  1. Corrections to the rho-parameter due to a heavy Higgs particle

    International Nuclear Information System (INIS)

    Bij, J.J. van der.

    1983-01-01

    The main part of this thesis is concerned with the calculation of the two-loop contribution to the rho-parameter, i.e. the ratio of charged and neutral vector boson masses, due to a heavy Higgs particle. It involves the calculation of a large number of Feynman diagrams. The result is that a contribution growing like m 2 exists (m = Higgs mass), but it does not correspond to the poles at n=3 in the non-linear model. First the model is introduced, the precise definition of rho is given and the formal connection with the non-linear model is derived. Then the one-loop infinities are calculated. It is shown that no m 2 corrections are observable in one loop and the log m 2 correction to rho is calculated. Finally the two-loop correction to rho is calculated. (Auth.)

  2. RhoC is essential for TGF-β1-induced invasive capacity of rat ascites hepatoma cells

    International Nuclear Information System (INIS)

    Mukai, M.; Endo, H.; Iwasaki, T.; Tatsuta, M.; Togawa, A.; Nakamura, H.; Inoue, M.

    2006-01-01

    Transforming growth factor-β1 (TGF-β1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-β1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-β1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-β1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-β1 in MM1 cells plays a critical role in TGF-β1-induced cell migration

  3. DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression.

    Science.gov (United States)

    Zaim, Merve; Isik, Sevim

    2018-04-25

    DNA topoisomerase IIβ (topo IIβ) is known to regulate neural differentiation by inducing the neuronal genes responsible for critical neural differentiation events such as neurite outgrowth and axon guidance. However, the pathways of axon growth controlled by topo IIβ have not been clarified yet. Microarray results of our previous study have shown that topo IIβ silencing in neural differentiated primary human mesenchymal stem cells (hMSCs) significantly alters the expression pattern of genes involved in neural polarity, axonal growth, and guidance, including Rho-GTPases. This study aims to further analyze the regulatory role of topo IIβ on the process of axon growth via regulation of Rho-GTPases. For this purpose, topo IIβ was silenced in neurally differentiated hMSCs. Cells lost their morphology because of topo IIβ deficiency, becoming enlarged and flattened. Additionally, a reduction in both neural differentiation efficiency and neurite length, upregulation in RhoA and Rock2, downregulation in Cdc42 gene expression were detected. On the other hand, cells were transfected with topo IIβ gene to elucidate the possible neuroprotective effect of topo IIβ overexpression on neural-induced hMSCs. Topo IIβ overexpression prompted all the cells to exhibit neural cell morphology as characterized by longer neurites. RhoA and Rock2 expressions were downregulated, whereas Cdc42 expression was upregulated. Nurr1 expression level correlated with topo IIβ in both topo IIβ-overexpressed and -silenced cells. Furthermore, differential translocation of Rho-GTPases was detected by immunostaining in response to topo IIβ. Our results suggest that topo IIβ deficiency could give rise to neurodegeneration through dysregulation of Rho-GTPases. However, further in-vivo research is needed to demonstrate if re-regulation of Rho GTPases by topo IIβ overexpression could be a neuroprotective treatment in the case of neurodegenerative diseases.

  4. Diffractive {rho} production with an AdS/QCD holographic wavefunction for the {rho} meson

    Energy Technology Data Exchange (ETDEWEB)

    Forshaw, Jeff [University of Manchester, Oxford Road, Manchester M13 9PL (United Kingdom); Sandapen, Ruben [Universite de Moncton, Moncton, N-B, E1A 3E9 (Canada) and Mount Allison University, Sackville, N-B, E46 1E6 (Canada)

    2013-04-15

    We report on the results of our recent research published in [1] that shows that AdS/QCD generates predictions for the rate of diffractive {rho}-meson electroproduction that are in agreement with data collected at the HERA electron-proton collider [2, 3]. Preliminary results of this research were presented in [4].

  5. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts

    Directory of Open Access Journals (Sweden)

    Max Nobis

    2017-10-01

    Full Text Available The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.

  6. Identification and characterization of a lymphocytic Rho-GTPase effector: rhotekin-2

    International Nuclear Information System (INIS)

    Collier, F.M.; Gregorio-King, C.C.; Gough, T.J.; Talbot, C.D.; Walder, K.; Kirkland, M.A.

    2004-01-01

    Rhotekin belongs to the group of proteins containing a Rho-binding domain that are target peptides (effectors) for the Rho-GTPases. We previously identified a novel cDNA with homology to human rhotekin and in this study we cloned and characterized the coding region of this novel 12-exon gene. The ORF encodes a 609 amino-acid protein comprising a Class I Rho-binding domain and pleckstrin homology (PH) domain. Cellular cDNA expression of this new protein, designated Rhotekin-2 (RTKN2), was shown in the cytosol and nucleus of CHO cells. Using bioinformatics and RTPCR we identified three major splice variants, which vary in both the Rho-binding and PH domains. Real-time PCR studies showed exclusive RTKN2 expression in pooled lymphocytes and further purification indicated sole expression in CD4 pos T-cells and bone marrow-derived B-cells. Gene expression was increased in quiescent T-cells but negligible in activated proliferating cells. In malignant samples expression was absent in myeloid leukaemias, low in most B-cell malignancies and CD8 pos T-cell malignancies, but very high in CD4 pos /CD8 pos T-lymphoblastic lymphoma. As the Rho family is critical in lymphocyte development and function, RTKN2 may play an important role in lymphopoiesis

  7. Molecular characterization of a novel RhoGAP, RRC-1 of the nematode Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Delawary, Mina; Nakazawa, Takanobu; Tezuka, Tohru; Sawa, Mariko; Iino, Yuichi; Takenawa, Tadaomi; Yamamoto, Tadashi

    2007-01-01

    The GTPase-activating proteins for Rho family GTPases (RhoGAP) transduce diverse intracellular signals by negatively regulating Rho family GTPase-mediated pathways. In this study, we have cloned and characterized a novel RhoGAP for Rac1 and Cdc42, termed RRC-1, from Caenorhabditis elegans. RRC-1 was highly homologous to mammalian p250GAP and promoted GTP hydrolysis of Rac1 and Cdc42 in cells. The rrc-1 mRNA was expressed in all life stages. Using an RRC-1::GFP fusion protein, we found that RRC-1 was localized to the coelomocytes, excretory cell, GLR cells, and uterine-seam cell in adult worms. These data contribute toward understanding the roles of Rho family GTPases in C. elegans

  8. Photoproduction of $\\rho^0$ in ultra--peripheral nuclear collisions at ALICE

    CERN Document Server

    Skjerdal, Kyrre

    2013-01-01

    Photoproduction of $\\rho^0$ mesons in ultra-peripheral Pb+Pb collisions has been studied by the ALICE Collaboration at the CERN LHC. The strong photon flux associated with relativistic charged nuclei leads to a very large cross section for exclusive photoproduction of $\\rho^0$ meson in interactions of the type $Pb + Pb \\rightarrow Pb + Pb + \\rho^0$. For a $\\rho^0$ produced at mid-rapidity at the LHC, the photon-nucleus center of mass energy is higher than in any previous experiment. The ALICE detector is a general purpose detector dedicated to study heavy--ion collisions. ALICE has excellent performance in the low $p_T$ region, and can reconstruct charged particle tracks with 0.1 GeV/c $\\leq p_T \\leq 100$ GeV/c. In this analysis all tracks were required to be within ALICE's central barrel. Analysis of data from the first heavy ion run at the LHC in 2010 will be discussed in this paper.

  9. RhoA: A therapeutic target for chronic myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Molli Poonam R

    2012-03-01

    Full Text Available Abstract Background Chronic Myeloid Leukemia (CML is a malignant pluripotent stem cells disorder of myeloid cells. In CML patients, polymorphonuclear leukocytes (PMNL the terminally differentiated cells of myeloid series exhibit defects in several actin dependent functions such as adhesion, motility, chemotaxis, agglutination, phagocytosis and microbicidal activities. A definite and global abnormality was observed in stimulation of actin polymerization in CML PMNL. Signalling molecules ras and rhoGTPases regulate spatial and temporal polymerization of actin and thus, a broad range of physiological processes. Therefore, status of these GTPases as well as actin was studied in resting and fMLP stimulated normal and CML PMNL. Methods To study expression of GTPases and actin, Western blotting and flow cytometry analysis were done, while spatial expression and colocalization of these proteins were studied by using laser confocal microscopy. To study effect of inhibitors on cell proliferation CCK-8 assay was done. Significance of differences in expression of proteins within the samples and between normal and CML was tested by using Wilcoxon signed rank test and Mann-Whitney test, respectively. Bivariate and partial correlation analyses were done to study relationship between all the parameters. Results In CML PMNL, actin expression and its architecture were altered and stimulation of actin polymerization was absent. Differences were also observed in expression, organization or stimulation of all the three GTPases in normal and CML PMNL. In normal PMNL, ras was the critical GTPase regulating expression of rhoGTPases and actin and actin polymerization. But in CML PMNL, rhoA took a central place. In accordance with these, treatment with rho/ROCK pathway inhibitors resulted in specific growth inhibition of CML cell lines. Conclusions RhoA has emerged as the key molecule responsible for functional defects in CML PMNL and therefore can be used as a

  10. Small G proteins in insulin action: Rab and Rho families at the crossroads of signal transduction and GLUT4 vesicle traffic.

    Science.gov (United States)

    Ishikura, S; Koshkina, A; Klip, A

    2008-01-01

    Insulin stimulates glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4). GLUT4 cycles between the intracellular compartments and the plasma membrane. GLUT4 traffic-regulating insulin signals are largely within the insulin receptor-insulin receptor substrate-phosphatidylinositol 3-kinase (IR-IRS-PI3K) axis. In muscle cells, insulin signal bifurcates downstream of the PI3K into one arm leading to the activation of the Ser/Thr kinases Akt and atypical protein kinase C, and another leading to the activation of Rho family protein Rac1 leading to actin remodelling. Activated Akt inactivates AS160, a GTPase-activating protein for Rab family small G proteins. Here we review the roles of Rab and Rho proteins, particularly Rab substrates of AS160 and Rac1, in insulin-stimulated GLUT4 traffic. We discuss: (1) how distinct steps in GLUT4 traffic may be regulated by discrete Rab proteins, and (2) the importance of Rac1 activation in insulin-induced actin remodelling in muscle cells, a key element for the net gain in surface GLUT4.

  11. Industrial PM2.5 cause pulmonary adverse effect through RhoA/ROCK pathway.

    Science.gov (United States)

    Yan, Junyan; Lai, Chia-Hsiang; Lung, Shih-Chun Candice; Chen, Chongjun; Wang, Wen-Cheng; Huang, Pin-I; Lin, Chia-Hua

    2017-12-01

    According to the Chinese Ministry of Health, industrial pollution-induced health impacts have been the leading cause of death in China. While industrial fine particulate matter (PM 2.5 ) is associated with adverse health effects, the major action mechanisms of different compositions of PM 2.5 are currently unclear. In this study, we treated normal human lung epithelial BEAS-2B cells with industrial organic and water-soluble PM 2.5 extracts under daily alveolar deposition dose to elucidate the molecular mechanisms underlying adverse pulmonary effects induced by PM 2.5 , including oxidative damage, inflammatory response, lung epithelial barrier dysfunction, and the recruitment of macrophages. We found that water-soluble PM 2.5 extracts caused more severe cytotoxic effects on BEAS-2B cells compared with that of organic extracts. Both organic and water-soluble PM 2.5 extracts induced activation of the RhoA/ROCK pathway. Inflammatory response, epithelial barrier dysfunction, and the activation of NF-кB caused by both PM 2.5 extracts were attenuated by ROCK inhibitor Y-27632. This indicated that both PM 2.5 extracts could cause damage to epithelial cells through RhoA/ROCK-dependent NF-кB activation. Furthermore, the upregulation of macrophage adhesion induced by both PM 2.5 extracts was also attenuated by Y-27632 in a co-culture model of macrophages and the epithelial cells. Therefore, our results support that industrial PM 2.5 extracts-induced activation of the RhoA/ROCK-dependent NF-кB pathway induces pulmonary adverse effect. Thus, pharmacological inhibition of ROCK activation might have therapeutic potential in preventing lung disease associated with PM 2.5 . Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Impact of liver fibrosis and fatty liver on T1rho measurements: A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Shuang Shuang; Li, Qing; Cheng, Yue; Shen, Wen [Dept. of Radiology, Tianjin First Center Hospital, Tianjin (China); Zhang, Yu; Zhuo, Zhi Zheng [Clinical Science, Philips Healthcare, Beijing (China); Zhao, Guiming [Dept. of Hepatology, Tianjin Second People' s Hospital, Tianjin (China)

    2017-11-15

    To investigate the liver T1rho values for detecting fibrosis, and the potential impact of fatty liver on T1rho measurements. This study included 18 healthy subjects, 18 patients with fatty liver, and 18 patients with liver fibrosis, who underwent T1rho MRI and mDIXON collections. Liver T1rho, proton density fat fraction (PDFF) and T2* values were measured and compared among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the T1rho values for detecting liver fibrosis. Liver T1rho values were correlated with PDFF, T2* values and clinical data. Liver T1rho and PDFF values were significantly different (p < 0.001), whereas the T2* (p = 0.766) values were similar, among the three groups. Mean liver T1rho values in the fibrotic group (52.6 ± 6.8 ms) were significantly higher than those of healthy subjects (44.9 ± 2.8 ms, p < 0.001) and fatty liver group (45.0 ± 3.5 ms, p < 0.001). Mean liver T1rho values were similar between healthy subjects and fatty liver group (p = 0.999). PDFF values in the fatty liver group (16.07 ± 10.59%) were significantly higher than those of healthy subjects (1.43 ± 1.36%, p < 0.001) and fibrosis group (1.07 ± 1.06%, p < 0.001). PDFF values were similar in healthy subjects and fibrosis group (p = 0.984). Mean T1rho values performed well to detect fibrosis at a threshold of 49.5 ms (area under the ROC curve, 0.855), had a moderate correlation with liver stiffness (r = 0.671, p = 0.012), and no correlation with PDFF, T2* values, subject age, or body mass index (p > 0.05). T1rho MRI is useful for noninvasive detection of liver fibrosis, and may not be affected with the presence of fatty liver.

  13. Control of Homeostasis and Dendritic Cell Survival by the GTPase RhoA

    DEFF Research Database (Denmark)

    Li, Shuai; Dislich, Bastian; Brakebusch, Cord H

    2015-01-01

    11b(-)CD8(+) and CD11b(+)Esam(hi) DC subsets, whereas CD11b(+)Esam(lo) DCs were not affected in conditional RhoA-deficient mice. Proteome analyses revealed a defective prosurvival pathway via PI3K/protein kinase B (Akt1)/Bcl-2-associated death promoter in the absence of RhoA. Taken together, our...... findings identify RhoA as a central regulator of DC homeostasis, and its deletion decreases DC numbers below critical thresholds for immune protection and homeostasis, causing aberrant compensatory DC proliferation....

  14. Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro

    NARCIS (Netherlands)

    Nieuw Amerongen, G.P. van; Koolwijk, P.; Versteilen, A.; Hinsbergh, V.W.M. van

    2003-01-01

    Objective - Growth factor-induced angiogenesis involves migration of endothelial cells (ECs) into perivascular areas and requires active remodeling of the endothelial F-actin cytoskeleton. The small GTPase RhoA previously has been implicated in vascular endothelial growth factor (VEGF)-induced

  15. RhoA activation and nuclearization marks loss of chondrocyte phenotype in crosstalk with Wnt pathway.

    Science.gov (United States)

    Öztürk, Ece; Despot-Slade, Evelin; Pichler, Michael; Zenobi-Wong, Marcy

    2017-11-15

    De-differentiation comprises a major drawback for the use of autologous chondrocytes in cartilage repair. Here, we investigate the role of RhoA and canonical Wnt signaling in chondrocyte phenotype. Chondrocyte de-differentiation is accompanied by an upregulation and nuclear localization of RhoA. Effectors of canonical Wnt signaling including β-catenin and YAP/TAZ are upregulated in de-differentiating chondrocytes in a Rho-dependent manner. Inhibition of Rho activation with C3 transferase inhibits nuclear localization of RhoA, induces expression of chondrogenic markers on 2D and enhances the chondrogenic effect of 3D culturing. Upregulation of chondrogenic markers by Rho inhibition is accompanied by loss of canonical Wnt signaling markers in 3D or on 2D whereas treatment of chondrocytes with Wnt-3a abrogates this effect. However, induction of canonical Wnt signaling inhibits chondrogenic markers on 2D but enhances chondrogenic re-differentiation on 2D with C3 transferase or in 3D. These data provide insights on the context-dependent role of RhoA and Wnt signaling in de-differentiation and on mechanisms to induce chondrogenic markers for therapeutic approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. RhoA-Mediated Functions in C3H10T1/2 Osteoprogenitors Are Substrate Topography Dependent.

    Science.gov (United States)

    Ogino, Yoichiro; Liang, Ruiwei; Mendonça, Daniela B S; Mendonça, Gustavo; Nagasawa, Masako; Koyano, Kiyoshi; Cooper, Lyndon F

    2016-03-01

    Surface topography broadly influences cellular responses. Adherent cell activities are regulated, in part, by RhoA, a member of the Rho-family of GTPases. In this study, we evaluated the influence of surface topography on RhoA activity and associated cellular functions. The murine mesenchymal stem cell line C3H10T1/2 cells (osteoprogenitor cells) were cultured on titanium substrates with smooth topography (S), microtopography (M), and nanotopography (N) to evaluate the effect of surface topography on RhoA-mediated functions (cell spreading, adhesion, migration, and osteogenic differentiation). The influence of RhoA activity in the context of surface topography was also elucidated using RhoA pharmacologic inhibitor. Following adhesion, M and N adherent cells developed multiple projections, while S adherent cells had flattened and widespread morphology. RhoA inhibitor induced remarkable longer and thinner cytoplasmic projections on all surfaces. Cell adhesion and osteogenic differentiation was topography dependent with S topography roughness dependent (S topography. Smooth surface adherent cells appear highly sensitive to RhoA function, while nano-scale topography adherent cell may utilize alternative cellular signaling pathway(s) to influence adherent cellular functions regardless of RhoA activity. © 2015 Wiley Periodicals, Inc.

  17. Inclusive and semi-inclusive rho0 production in π-p interactions at 147 GeV/c

    International Nuclear Information System (INIS)

    Fong, D.; Heller, M.; Shapiro, A.M.; Widgoff, M.; Bruyant, F.; Bogert, D.; Johnson, M.; Burnstein, R.; Fu, C.; Petersen, D.; Robertson, M.; Rubin, H.; Sard, R.; Snyder, A.; Tortora, J.; Alyea, D.; Chien, C.-Y.; Lucas, P.; Pevsner, A.; Zdanis, R.; Brau, J.; Grunhaus, J.; Hafen, E.S.; Hulsizer, R.I.; Karshon, U.; Kistiakowsky, V.; Levy, A.; Napier, A.; Pless, I.A.; Trepagnier, P.C.; Wolfson, J.; Yamamoto, R.K.; Cohn, H.; Ou, T.C.; Plano, R.; Watts, T.; Brucker, E.; Koller, E.; Stamer, P.; Taylor, S.; Bugg, W.; Condo, G.; Handler, T.; Hart, E.; Kraybill, H.; Ljung, D.; Ludlam, T.; Taft, H.D.

    1975-01-01

    Data on inclusive and semi-inclusive rho 0 production in 147 GeV/c π - p interactions are presented. A total cross section of 7.3+-1.3 mb is found. Most of this cross section is found in the lower topology events ( 2 dependence of rho 0 production, sub(rho 0 ) per event, and the rho 0 /π + ratios are also discussed. (Auth.)

  18. RhoA Drives T-Cell Activation and Encephalitogenic Potential in an Animal Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Alba Manresa-Arraut

    2018-05-01

    Full Text Available T-cells are known to be intimately involved in the pathogenesis of multiple sclerosis (MS and its animal model experimental autoimmune encephalomyelitis (EAE. T-cell activation is controlled by a range of intracellular signaling pathways regulating cellular responses such as proliferation, cytokine production, integrin expression, and migration. These processes are crucial for the T-cells’ ability to mediate inflammatory processes in autoimmune diseases such as MS. RhoA is a ubiquitously expressed small GTPase well described as a regulator of the actin cytoskeleton. It is essential for embryonic development and together with other Rho GTPases controls various cellular processes such as cell development, shaping, proliferation, and locomotion. However, the specific contribution of RhoA to these processes in T-cells in general, and in autoreactive T-cells in particular, has not been fully characterized. Using mice with a T-cell specific deletion of the RhoA gene (RhoAfl/flLckCre+, we investigated the role of RhoA in T-cell development, functionality, and encephalitogenic potential in EAE. We show that lack of RhoA specifically in T-cells results in reduced numbers of mature T-cells in thymus and spleen but normal counts in peripheral blood. EAE induction in RhoAfl/flLckCre+ mice results in significantly reduced disease incidence and severity, which coincides with a reduced CNS T-cell infiltration. Besides presenting reduced migratory capacity, both naïve and autoreactive effector T-cells from RhoAfl/flLckCre+ mice show decreased viability, proliferative capacity, and an activation profile associated with reduced production of Th1 pro-inflammatory cytokines. Our study demonstrates that RhoA is a central regulator of several archetypical T-cell responses, and furthermore points toward RhoA as a new potential therapeutic target in diseases such as MS, where T-cell activity plays a central role.

  19. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

    International Nuclear Information System (INIS)

    He, Mian; Cheng, Yang; Li, Wen; Liu, Qiongshan; Liu, Junxiu; Huang, Jinghe; Fu, Xiaodong

    2010-01-01

    The elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy

  20. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade

    Directory of Open Access Journals (Sweden)

    Huang Jinghe

    2010-04-01

    Full Text Available Abstract Background The elevated expression of vascular endothelial growth factor C (VEGF-C is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis. However, the direct impact of VEGF-C on cervical cancer cell motility remains largely unknown. Methods In this study, we investigated the effects of VEGF-C on actin cytoskeleton remodeling and on cervical cancer cell migration and invasion and how the actin-regulatory protein, moesin regulated these effects through RhoA/ROCK-2 signaling pathway. Results On cervical carcinoma cell line SiHa cells, exposure of VEGF-C triggered remodeling of the actin cytoskeleton and the formation of membrane ruffles, which was required for cell movement. VEGF-C significantly enhanced SiHa cells horizontal migration and three-dimensional invasion into matrices. These actions were dependent on increased expression and phosphorylation of the actin-regulatory protein moesin and specific moesin siRNA severely impaired VEGF-C stimulated-cell migration. The extracellular small GTPase RhoA/ROCK-2 cascade mediated the increased moesin expression and phosphorylation, which was discovered by the use of Y-27632, a specific inhibitor of Rho kinase and by transfected constitutively active, dominant-negative RhoA as well as ROCK-2 SiRNA. Furthermore, in the surgical cervical specimen from the patients with FIGO stage at cervical intra-epithelial neoplasia and I-II cervical squamous cell carcinoma, the expression levels of moesin were found to be significantly correlated with tumor malignancy and metastasis. Conclusions These results implied that VEGF-C promoted cervical cancer metastasis by upregulation and activation of moesin protein through RhoA/ROCK-2 pathway. Our findings offer new insight into the role of VEGF-C on cervical cancer progression and may provide potential targets for cervical cancer therapy.

  1. 42 CFR 493.859 - Standard; ABO group and D (Rho) typing.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; ABO group and D (Rho) typing. 493.859 Section 493.859 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN..., Or Any Combination of These Tests § 493.859 Standard; ABO group and D (Rho) typing. (a) Failure to...

  2. Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation.

    Science.gov (United States)

    Stakaitytė, Gabrielė; Nwogu, Nnenna; Dobson, Samuel J; Knight, Laura M; Wasson, Christopher W; Salguero, Francisco J; Blackbourn, David J; Blair, G Eric; Mankouri, Jamel; Macdonald, Andrew; Whitehouse, Adrian

    2018-01-15

    Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β 1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC. IMPORTANCE Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds

  3. Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiang; Zhao, Fang [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Lv, Zhong-ming; Shi, Wei-qin [Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (China); Zhang, Lu-yong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing (China); State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Yan, Ming, E-mail: brookming@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

    2016-11-01

    Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

  4. Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

    International Nuclear Information System (INIS)

    Wang, Xiang; Zhao, Fang; Lv, Zhong-ming; Shi, Wei-qin; Zhang, Lu-yong; Yan, Ming

    2016-01-01

    Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

  5. Ornithine decarboxylase regulates the activity and localization of rhoA via polyamination

    International Nuclear Information System (INIS)

    Maekitie, Laura T.; Kanerva, Kristiina; Andersson, Leif C.

    2009-01-01

    Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. Polyamines and ODC are connected to cell proliferation and transformation. Resting cells display a low ODC activity while normal, proliferating cells display fluctuations in ODC activity that coincide with changes in the actin cytoskeleton during the cell cycle. Cancerous cells display constitutively elevated ODC activity. Overexpression of ODC in NIH 3T3 fibroblasts induces a transformed phenotype. The cytoskeletal rearrangements during cytokinesis and cell transformation are intimately coupled to the ODC activity but the molecular mechanisms have remained elusive. In this study we investigated how ODC and polyamines influence the organization of the cytoskeleton. Given that the small G-proteins of the rho family are key modulators of the actin cytoskeleton, we investigated the molecular interactions of rhoA with ODC and polyamines. Our results show that transglutaminase-catalyzed polyamination of rhoA regulates its activity. The polyamination status of rhoA crucially influences the progress of the cell cycle as well as the rate of transformation of rat fibroblasts infected with temperature-sensitive v-src. We also show that ODC influences the intracellular distribution of rhoA. These findings provide novel insights into the mechanisms by which ODC and polyamines regulate the dynamics of the cytoskeleton during cell proliferation and transformation

  6. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

    Science.gov (United States)

    Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J Bruce; Reddy, Ravinder

    2006-11-01

    In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models

  7. The 'invisible hand': regulation of RHO GTPases by RHOGDIs.

    Science.gov (United States)

    Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

    2011-07-22

    The 'invisible hand' is a term originally coined by Adam Smith in The Theory of Moral Sentiments to describe the forces of self-interest, competition and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle.

  8. The invisible hand: regulation of RHO GTPases by RHOGDIs

    Science.gov (United States)

    Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

    2011-01-01

    Preface The 'invisible hand' is a term originally coined by Adam Smith in the Theory of Moral Sentiments to describe the forces of self-interest, competition, and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle. PMID:21779026

  9. Nanofibrillar scaffolds induce preferential activation of Rho GTPases in cerebral cortical astrocytes

    Science.gov (United States)

    Tiryaki, Volkan Mujdat; Ayres, Virginia M; Khan, Adeel A; Ahmed, Ijaz; Shreiber, David I; Meiners, Sally

    2012-01-01

    Cerebral cortical astrocyte responses to polyamide nanofibrillar scaffolds versus poly-L-lysine (PLL)-functionalized planar glass, unfunctionalized planar Aclar coverslips, and PLL-functionalized planar Aclar surfaces were investigated by atomic force microscopy and immunocytochemistry. The physical properties of the cell culture environments were evaluated using contact angle and surface roughness measurements and compared. Astrocyte morphological responses, including filopodia, lamellipodia, and stress fiber formation, and stellation were imaged using atomic force microscopy and phalloidin staining for F-actin. Activation of the corresponding Rho GTPase regulators was investigated using immunolabeling with Cdc42, Rac1, and RhoA. Astrocytes cultured on the nanofibrillar scaffolds showed a unique response that included stellation, cell–cell interactions by stellate processes, and evidence of depression of RhoA. The results support the hypothesis that the extracellular environment can trigger preferential activation of members of the Rho GTPase family, with demonstrable morphological consequences for cerebral cortical astrocytes. PMID:22915841

  10. Viral activation of MK2-hsp27-p115RhoGEF-RhoA signaling axis causes cytoskeletal rearrangements, p-body disruption and ARE-mRNA stabilization.

    Directory of Open Access Journals (Sweden)

    Jennifer A Corcoran

    2015-01-01

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is the infectious cause of several AIDS-related cancers, including the endothelial cell (EC neoplasm Kaposi's sarcoma (KS. KSHV-infected ECs secrete abundant host-derived pro-inflammatory molecules and angiogenic factors that contribute to tumorigenesis. The precise contributions of viral gene products to this secretory phenotype remain to be elucidated, but there is emerging evidence for post-transcriptional regulation. The Kaposin B (KapB protein is thought to contribute to the secretory phenotype in infected cells by binding and activating the stress-responsive kinase MK2, thereby selectively blocking decay of AU-rich mRNAs (ARE-mRNAs encoding pro-inflammatory cytokines and angiogenic factors. Processing bodies (PBs are cytoplasmic ribonucleoprotein foci in which ARE-mRNAs normally undergo rapid 5' to 3' decay. Here, we demonstrate that PB dispersion is a feature of latent KSHV infection, which is dependent on kaposin protein expression. KapB is sufficient to disperse PBs, and KapB-mediated ARE-mRNA stabilization could be partially reversed by treatments that restore PBs. Using a combination of genetic and chemical approaches we provide evidence that KapB-mediated PB dispersion is dependent on activation of a non-canonical Rho-GTPase signaling axis involving MK2, hsp27, p115RhoGEF and RhoA. PB dispersion in latently infected cells is likewise dependent on p115RhoGEF. In addition to PB dispersion, KapB-mediated RhoA activation in primary ECs caused actin stress fiber formation, increased cell motility and angiogenesis; these effects were dependent on the activity of the RhoA substrate kinases ROCK1/2. By contrast, KapB-mediated PB dispersion occurred in a ROCK1/2-independent manner. Taken together, these observations position KapB as a key contributor to viral reprogramming of ECs, capable of eliciting many of the phenotypes characteristic of KS tumor cells, and strongly contributing to the post

  11. Search for the Decay B^0 -> a^\\pm_1 \\rho^\\mp

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.

    2006-05-10

    The authors present a search for the rare B-meson decay B{sup 0} {yields} {alpha}{sub 1}{sup {+-}}{rho}{sup {-+}} with {alpha}{sub 1}{sup {+-}} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup {+-}}. We use (110 {+-} 1.2) x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEp-II asymmetric-energy B Factory at SLAC. They obtain an upper limit of 30 x 10{sup -6} (90% C.L.) for the branching fraction product {Beta}(B{sup 0} {yields} {alpha}{sub 1}{sup {+-}}{rho}{sup {-+}}) {Beta}({alpha}{sub 1}{sup {+-}} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup {+-}}), where they assume that the {alpha}{sub 1}{sup {+-}} decays exclusively to {rho}{sup 0}{pi}{sup {+-}}.

  12. Rho, a Fraction From Rhodiola crenulate, Ameliorates Hepatic Steatosis in Mice Models

    Directory of Open Access Journals (Sweden)

    Qin Yi

    2018-03-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD, which is developed from hepatic steatosis, is increasing worldwide. However, no specific drugs for NAFLD have been approved yet. To observe the effects of Rho, a fraction from Rhodiola crenulate, on non-alcoholic hepatic steatosis, three mouse models with characteristics of NAFLD were used including high-fat diet (HFD-induced obesity (DIO mice, KKAy mice, and HFD combined with tetracycline stimulated Model-T mice. Hepatic lipid accumulation was determined via histopathological analysis and/or hepatic TG determination. The responses to insulin were evaluated by insulin tolerance test (ITT, glucose tolerance test (GTT, and hyperinsulinemic-euglycemic clamp, respectively. The pathways involved in hepatic lipid metabolism were observed via western-blot. Furthermore, the liver microcirculation was observed by inverted microscopy. The HPLC analysis indicated that the main components of Rho were flavan polymers. The results of histopathological analysis showed that Rho could ameliorate hepatic steatosis in DIO, KKAy, and Model-T hepatic steatosis mouse models, respectively. After Rho treatment in DIO mice, insulin resistance was improved with increasing glucose infusion rate (GIR in hyperinsulinemic-euglycemic clamp, and decreasing areas under the blood glucose-time curve (AUC in both ITT and GTT; the pathways involved in fatty acid uptake and de novo lipogenesis were both down-regulated, respectively. However, the pathways involved in beta-oxidation and VLDL-export on hepatic steatosis were not changed significantly. The liver microcirculation disturbances were also improved by Rho in DIO mice. These results suggest that Rho is a lead nature product for hepatic steatosis treatment. The mechanism is related to enhancing insulin sensitivity, suppressing fatty acid uptake and inhibiting de novo lipogenesis in liver.

  13. Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development.

    Science.gov (United States)

    Liu, Yingwei; Song, Na; Ren, Kexing; Meng, Shenglan; Xie, Yao; Long, Qida; Chen, Xiancheng; Zhao, Xia

    2013-01-01

    RhoB, a member of small GTPases belonging to the Ras protein superfamily, might have a suppressive activity in cancer progression. Here, expression of RhoB gene was evaluated in human benign, borderline and malignant ovary tumors by immunostaining, with normal ovary tissue as control. Malignant tumors were assessed according to Federation Internationale de Gynecologie Obstetrique (FIGO) guidelines and classified in stage I-IV. Revivification of RhoB gene was investigated by analyzing the effect of histone deacetylase (HDAC) inhibitor trichostatin (TSA) and methyltransferase inhibitor 5-azacytidine (5-Aza) on ovarian cancer cells via RT-PCR and western blot. Apoptosis of ovary cancer cells was detected using flowcytometry and fluorescence microscopy. Subsequently, RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly or lost in the majority of ovarian cancer specimen (Pcancer cells, but 5-Aza couldn't. Interference into Revivification of RhoB gene results in reduction of ovary carcinoma cell apoptosis. It is proposed that loss of RhoB expression occurs frequently in ovary carcinogenesis and progression and its expression could be regulated by histone deacetylation but not by promoter hypermethylation, which may serve as a prospective gene treatment target for the patients with ovarian malignancy not responding to standard therapies.

  14. A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the Transcreener GDP Assay.

    Science.gov (United States)

    Reichman, Melvin; Schabdach, Amanda; Kumar, Meera; Zielinski, Tom; Donover, Preston S; Laury-Kleintop, Lisa D; Lowery, Robert G

    2015-12-01

    Ras homologous (Rho) family GTPases act as molecular switches controlling cell growth, movement, and gene expression by cycling between inactive guanosine diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations. Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by accelerating GDP dissociation to allow formation of the active, GTP-bound complex. Rho proteins are directly involved in cancer pathways, especially cell migration and invasion, and inhibiting GEFs holds potential as a therapeutic strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF activity suitable for high-throughput screening (HTS) are limited. We developed a simple, generic biochemical assay method for measuring GEF activity based on the fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase catalytic cycle, and thus addition of a GEF causes an increase in steady-state GTPase activity. We used the Transcreener GDP Assay, which relies on selective immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42, RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and far red fluorescence polarization (FP) readout, and it should be broadly applicable to diverse Rho GEF/GTPase pairs. © 2015 Society for Laboratory Automation and Screening.

  15. The Na+–H+ exchanger-1 induces cytoskeletal changes involving reciprocal RhoA and Rac1 signaling, resulting in motility and invasion in MDA-MB-435 cells

    International Nuclear Information System (INIS)

    Paradiso, Angelo; Cardone, Rosa Angela; Bellizzi, Antonia; Bagorda, Anna; Guerra, Lorenzo; Tommasino, Massimo; Casavola, Valeria; Reshkin, Stephan J

    2004-01-01

    pattern of RhoA and Rac1 regulation found for NHE1 activity was observed in both basal and serum deprivation dependent increases in motility, invasion and actin cytoskeletal organization. Our findings suggest that the reported antagonistic roles of RhoA and Rac1 in cell motility/invasion and cytoskeletal organization may be due, in part, to their concerted action on NHE1 activity as a convergence point

  16. Exclusive $\\rho^0$ Meson Photoproduction with a Leading Neutron at HERA

    CERN Document Server

    Andreev, V.; Begzsuren, K.; Belousov, A.; Bolz, A.; Boudry, V.; Brandt, G.; Brisson, V.; Britzger, D.; Buniatyan, A.; Bylinkin, A.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cerny, K.; Chekelian, V.; Contreras, J.G.; Cvach, J.; Dainton, J.B.; Daum, K.; Diaconu, C.; Dobre, M.; Dodonov, V.; Eckerlin, G.; Egli, S.; Elsen, E.; Favart, L.; Fedotov, A.; Feltesse, J.; Ferencei, J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, S.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Grebenyuk, A.; Greenshaw, T.; Grindhammer, G.; Haidt, D.; Henderson, R.C.W.; Hladký, J.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Huber, F.; Jacquet, M.; Janssen, X.; Jung, H.; Kapichine, M.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kogler, R.; Kostka, P.; Kretzschmar, J.; Krüger, K.; Landon, M.P.J.; Lange, W.; Laycock, P.; Lebedev, A.; Levonian, S.; Lipka, K.; List, B.; List, J.; Lobodzinski, B.; Malinovski, E.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meyer, A.B.; Meyer, H.; Meyer, J.; Mikocki, S.; Morozov, A.; Müller, K.; Naumann, Th.; Newman, P.R.; Niebuhr, C.; Nowak, G.; Olsson, J.E.; Ozerov, D.; Pascaud, C.; Patel, G.D.; Perez, E.; Petrukhin, A.; Picuric, I.; Pirumov, H.; Pitzl, D.; Plačakytė, R.; Pokorny, B.; Polifka, R.; Povh, B.; Radescu, V.; Raicevic, N.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Rusakov, S.; Šálek, D.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schoeffel, L.; Schöning, A.; Sefkow, F.; Shushkevich, S.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Steder, M.; Stella, B.; Straumann, U.; Sykora, T.; Thompson, P.D.; Traynor, D.; Truöl, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Valkárová, A.; Vallée, C.; Van Mechelen, P.; Vazdik, Y.; Wegener, D.; Wünsch, E.; Žáček, J.; Zhang, Z.; Žlebčík, R.; Zohrabyan, H.; Zomer, F.

    2016-01-23

    A first measurement is presented of exclusive photoproduction of $\\rho^0$ mesons associated with leading neutrons at HERA. The data were taken with the H1 detector in the years $2006$ and $2007$ at a centre-of-mass energy of $\\sqrt{s}=319$ GeV and correspond to an integrated luminosity of $1.16$ pb$^{-1}$. The $\\rho^0$ mesons with transverse momenta $p_T0.35$, are detected in the Forward Neutron Calorimeter. The phase space of the measurement is defined by the photon virtuality $Q^2 < 2$ GeV$^2$, the total energy of the photon-proton system $20 < W_{\\gamma p} < 100$ GeV and the polar angle of the leading neutron $\\theta_n < 0.75$ mrad. The cross section of the reaction $\\gamma p \\to \\rho^0 n \\pi^+$ is measured as a function of several variables. The data are interpreted in terms of a double peripheral process, involving pion exchange at the proton vertex followed by elastic photoproduction of a $\\rho^0$ meson on the virtual pion. In the framework of one-pion-exchange dominance the elastic cross se...

  17. Inclusive rho0 production in anti νsub(μ)p charged current interactions

    International Nuclear Information System (INIS)

    Graessler, H.; Lanske, D.; Schulte, R.; Barnham, K.W.J.; Clayton, E.F.; Hamisi, F.; Miller, D.B.; Mobayyen, M.M.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1986-01-01

    Inclusive rho 0 production has been studied in antineutrino-proton charged current interactions, using a sample of 3340 events obtained in BEBC filled with hydrogen and exposed to the CERN wideband antineutrino beam. An average multiplicity of 0.11+-0.02 rho 0 per event at a mean hadronic mass W of 4.2 GeV is observed. The rho 0 production characteristics are determined as functions of psub(T), chisub(F), and z. The ratio rho 0 /'π 0 ' is found to be low at small z values consistent with centrally produced pions coming mainly from resonances. At large z values this ratio approaches 0.45+-0.15 which is compatible with a vector/pseudoscalar meson direct production ratio of one. The results are compared with those obtained from neutrino-proton interactions in the same experimental set-up. (orig.)

  18. Regulation of white and brown adipocyte differentiation by RhoGAP DLC1.

    Directory of Open Access Journals (Sweden)

    Choon Kiat Sim

    Full Text Available Adipose tissues constitute an important component of metabolism, the dysfunction of which can cause obesity and type II diabetes. Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1, a Rho GTPase Activating Protein (RhoGAP previously studied for its function in liver cancer. We identified Dlc1 as a super-enhancer associated gene in both white and brown adipocytes through analyzing the genome-wide binding profiles of PPARγ, the master regulator of adipogenesis. We further observed that Dlc1 expression increases during differentiation, and knockdown of Dlc1 by siRNA in white adipocytes reduces the formation of lipid droplets and the expression of fat marker genes. Moreover, knockdown of Dlc1 in brown adipocytes reduces expression of brown fat-specific genes and diminishes mitochondrial respiration. Dlc1-/- knockout mouse embryonic fibroblasts show a complete inability to differentiate into adipocytes, but this phenotype can be rescued by inhibitors of Rho-associated kinase (ROCK and filamentous actin (F-actin, suggesting the involvement of Rho pathway in DLC1-regulated adipocyte differentiation. Furthermore, PPARγ binds to the promoter of Dlc1 gene to regulate its expression during both white and brown adipocyte differentiation. These results identify DLC1 as an activator of white and brown adipocyte differentiation, and provide a molecular link between PPARγ and Rho pathways.

  19. Mycobacterium tuberculosis Rho is an NTPase with distinct kinetic properties and a novel RNA-binding subdomain.

    Directory of Open Access Journals (Sweden)

    Anirban Mitra

    Full Text Available Two mechanisms--factor independent and dependent termination--ensure the completion of RNA synthesis in eubacteria. Factor-dependent mechanism relies on the Rho protein to terminate transcription by interacting with RNA polymerase. Although well studied in Escherichia coli, the properties of the Rho homologs from most bacteria are not known. The rho gene is unusually large in genus Mycobacterium and other members of actinobacteria, having ∼150 additional residues towards the amino terminal end. We describe the distinct properties of Rho from Mycobacterium tuberculosis. It is an NTPase with a preference for purine nucleoside triphosphates with kinetic properties different from E. coli homolog and an ability to use various RNA substrates. The N-terminal subdomain of MtbRho can bind to RNA by itself, and appears to contribute to the interaction of the termination factor with RNAs. Furthermore, the interaction with RNA induces changes in conformation and oligomerization of MtbRho.

  20. Activation of G protein-coupled estrogen receptor 1 induces coronary artery relaxation via Epac/Rap1-mediated inhibition of RhoA/Rho kinase pathway in parallel with PKA.

    Directory of Open Access Journals (Sweden)

    Xuan Yu

    Full Text Available Previously, we reported that cAMP/PKA signaling is involved in GPER-mediated coronary relaxation by activating MLCP via inhibition of RhoA pathway. In the current study, we tested the hypothesis that activation of GPER induces coronary artery relaxation via inhibition of RhoA/Rho kinase pathway by cAMP downstream targets, exchange proteins directly activated by cAMP (Epac as well as PKA. Our results show that Epac inhibitors, brefeldin A (BFA, 50 μM, or ESI-09 (20 μM, or CE3F4 (100 μM, all partially inhibited porcine coronary artery relaxation response to the selective GPER agonist, G-1 (0.3-3 μM; while concurrent administration of BFA and PKI (5 μM, a PKA inhibitor, almost completely blocked the relaxation effect of G-1. The Epac specific agonist, 8-CPT-2Me-cAMP (007, 1-100 μM, induced a concentration-dependent relaxation response. Furthermore, the activity of Ras-related protein 1 (Rap1 was up regulated by G-1 (1 μM treatment of porcine coronary artery smooth muscle cells (CASMCs. Phosphorylation of vasodilator-stimulated phosphoprotein (p-VASP was elevated by G-1 (1 μM treatment, but not by 007 (50 μM; and the effect of G-1 on p-VASP was blocked by PKI, but not by ESI-09, an Epac antagonist. RhoA activity was similarly down regulated by G-1 and 007, whereas ESI-09 restored most of the reduced RhoA activity by G-1 treatment. Furthermore, G-1 decreased PGF2α-induced p-MYPT1, which was partially reversed with either ESI-09 or PKI; whereas, concurrent administration of ESI-09 and PKI totally prevented the inhibitory effect of G-1. The inhibitory effects of G-1 on p- MLC levels in CASMCs were mostly restored by either ESI-09 or PKI. These results demonstrate that activation of GPER induces coronary artery relaxation via concurrent inhibition of RhoA/Rho kinase by Epac/Rap1 and PKA. GPER could be a potential drug target for preventing and treating cardiovascular diseases.

  1. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

    Science.gov (United States)

    Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

    2011-08-01

    Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

  2. Human Mammary Epithelial Cell Transformation by Rho GTPase Through a Novel Mechanism

    Science.gov (United States)

    2009-08-01

    87: 635-44. 18. Burbelo P, Wellstein A, Pestell RG. Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res Treat 2004; 84...Burbelo P, Wellstein A, Pestell RG. Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res Treat 2004;84:43–8. 19. Band V

  3. Comparison of Gasoline Direct-Injection (GDI) and Port Fuel Injection (PFI) Vehicle Emissions: Emission Certification Standards, Cold-Start, Secondary Organic Aerosol Formation Potential, and Potential Climate Impacts.

    Science.gov (United States)

    Saliba, Georges; Saleh, Rawad; Zhao, Yunliang; Presto, Albert A; Lambe, Andrew T; Frodin, Bruce; Sardar, Satya; Maldonado, Hector; Maddox, Christine; May, Andrew A; Drozd, Greg T; Goldstein, Allen H; Russell, Lynn M; Hagen, Fabian; Robinson, Allen L

    2017-06-06

    Recent increases in the Corporate Average Fuel Economy standards have led to widespread adoption of vehicles equipped with gasoline direct-injection (GDI) engines. Changes in engine technologies can alter emissions. To quantify these effects, we measured gas- and particle-phase emissions from 82 light-duty gasoline vehicles recruited from the California in-use fleet tested on a chassis dynamometer using the cold-start unified cycle. The fleet included 15 GDI vehicles, including 8 GDIs certified to the most-stringent emissions standard, superultra-low-emission vehicles (SULEV). We quantified the effects of engine technology, emission certification standards, and cold-start on emissions. For vehicles certified to the same emissions standard, there is no statistical difference of regulated gas-phase pollutant emissions between PFIs and GDIs. However, GDIs had, on average, a factor of 2 higher particulate matter (PM) mass emissions than PFIs due to higher elemental carbon (EC) emissions. SULEV certified GDIs have a factor of 2 lower PM mass emissions than GDIs certified as ultralow-emission vehicles (3.0 ± 1.1 versus 6.3 ± 1.1 mg/mi), suggesting improvements in engine design and calibration. Comprehensive organic speciation revealed no statistically significant differences in the composition of the volatile organic compounds emissions between PFI and GDIs, including benzene, toluene, ethylbenzene, and xylenes (BTEX). Therefore, the secondary organic aerosol and ozone formation potential of the exhaust does not depend on engine technology. Cold-start contributes a larger fraction of the total unified cycle emissions for vehicles meeting more-stringent emission standards. Organic gas emissions were the most sensitive to cold-start compared to the other pollutants tested here. There were no statistically significant differences in the effects of cold-start on GDIs and PFIs. For our test fleet, the measured 14.5% decrease in CO 2 emissions from GDIs was much greater than

  4. Termination factor Rho: From the control of pervasive transcription to cell fate determination in Bacillus subtilis

    Science.gov (United States)

    Nicolas, Pierre; Repoila, Francis; Bardowski, Jacek; Aymerich, Stéphane

    2017-01-01

    In eukaryotes, RNA species originating from pervasive transcription are regulators of various cellular processes, from the expression of individual genes to the control of cellular development and oncogenesis. In prokaryotes, the function of pervasive transcription and its output on cell physiology is still unknown. Most bacteria possess termination factor Rho, which represses pervasive, mostly antisense, transcription. Here, we investigate the biological significance of Rho-controlled transcription in the Gram-positive model bacterium Bacillus subtilis. Rho inactivation strongly affected gene expression in B. subtilis, as assessed by transcriptome and proteome analysis of a rho–null mutant during exponential growth in rich medium. Subsequent physiological analyses demonstrated that a considerable part of Rho-controlled transcription is connected to balanced regulation of three mutually exclusive differentiation programs: cell motility, biofilm formation, and sporulation. In the absence of Rho, several up-regulated sense and antisense transcripts affect key structural and regulatory elements of these differentiation programs, thereby suppressing motility and biofilm formation and stimulating sporulation. We dissected how Rho is involved in the activity of the cell fate decision-making network, centered on the master regulator Spo0A. We also revealed a novel regulatory mechanism of Spo0A activation through Rho-dependent intragenic transcription termination of the protein kinase kinB gene. Altogether, our findings indicate that distinct Rho-controlled transcripts are functional and constitute a previously unknown built-in module for the control of cell differentiation in B. subtilis. In a broader context, our results highlight the recruitment of the termination factor Rho, for which the conserved biological role is probably to repress pervasive transcription, in highly integrated, bacterium-specific, regulatory networks. PMID:28723971

  5. A preliminary study of the T1rho values of normal knee cartilage using 3 T-MRI

    International Nuclear Information System (INIS)

    Goto, Hajimu; Iwama, Yuki; Fujii, Masahiko; Aoyama, Nobukazu; Kubo, Seiji; Kuroda, Ryosuke; Ohno, Yoshiharu; Sugimura, Kazuro

    2012-01-01

    Introduction: To investigate the degree of the effect of aging and weight-bearing on T1rho values in normal cartilage. Materials and methods: Thirty-two asymptomatic patients were examined using 3.0-T magnetic resonance imaging (MRI) to determine knee cartilage T1rho values and T2 values. The femoral and tibial cartilage was divided into weight-bearing (WB-Rs) and less-weight-bearing (LWB-Rs) regions. Single regression analysis was used to assess the relationship between cartilage T1rho values and age and between T2 values and age. Analysis of variance and post hoc-testing were used to evaluate differences in WB-Rs and LWB-Rs cartilage T1rho values and T2 values. Multiple linear regression modeling was performed to predict cartilage T1rho values. Results: Cartilage T1rho values correlated positively with age for all cartilage regions tested (p < 0.001). There were no significant correlations between cartilage T2 values and age. In both the medial femoral and tibial cartilage, T1rho values were significantly higher in WB-Rs than in LWB-Rs (p < 0.05). There were no significant differences in T2 values between WB-Rs and LWB-Rs. Multiple linear regression analysis showed that both age and weight-bearing were significant predictors of increased medial knee cartilage T1rho values (p < 0.001). Conclusions: Aging and the degree of weight-bearing correlate with the change in cartilage T1rho values. Based on multiple regression modeling, aging may be a more important factor than weight-bearing for cartilage T1rho values.

  6. Role of the strange quark in the rho(770) meson

    Energy Technology Data Exchange (ETDEWEB)

    Molina Peralta, Raquel [George Washington Univ., Washington, DC (United States); Guo, Dehua [George Washington Univ., Washington, DC (United States); Hu, B. [George Washington Univ., Washington, DC (United States); Alexandru, Andrei; Doering, Michael [George Washington Univ., Washington, DC (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2017-03-01

    Recently, the GWU lattice group has evaluated high-precision phase-shift data for $\\pi\\pi$ scattering in the $I = 1$, $J = 1$ channel. Unitary Chiral Perturbation Theory describes these data well around the resonance region and for different pion masses. Moreover, it allows to extrapolate to the physical point and estimate the effect of the missing $K\\bar{K}$ channel in the two-flavor lattice calculation. The absence of the strange quark in the lattice data leads to a lower $\\rho$ mass, and the analysis with U$\\chi$PT shows that the $K \\bar{K}$ channel indeed pushes the $\\pi\\pi$-scattering phase shift upward, having a surprisingly large effect on the $\\rho$-mass. The inelasticity is shown to be compatible with the experimental data. The analysis is then extended to all available two-flavor lattice simulations and similar mass shifts are observed. Chiral extrapolations of $N_f = 2 + 1$ lattice simulations for the $\\rho(770)$ are also reported.

  7. Numerical studies of spray breakup in a gasoline direct injection (GDI engine

    Directory of Open Access Journals (Sweden)

    Jafarmadar Samad

    2011-01-01

    Full Text Available The objective of this study is to investigate Spray Breakup process of sprays injected from single and two-hole nozzles for gasoline direct Injection (GDI engines by using three dimensional CFD code. Spray characteristics were examined for spray tip penetration and other characteristics including: the vapor phase concentration distribution and droplet spatial distribution, which were acquired using the computational fluid dynamics (CFD simulation. Results showed that as the hole-axis-angle (γ of the two-hole nozzle decreased, the droplet coalescence increased and vapor mass decreased. The spray with cone angle (θ0 5 deg for single hole nozzle has the longest spray tip penetration and the spray with the γ of 30 deg and spray cone angle θ0=30 deg for two hole nozzles had the shortest one. Also, when the spray cone angle (θ0 and hole-axis-angle (γ increased from 5 to 30 deg, the Sauter mean diameter (SMD decreased for both single-hole and two-hole nozzles used in this study. For a single-hole nozzle, when spray cone angle increased from 5 to 30 deg, the vaporization rate very much because of low level of coalescence. The result of model for tip penetration is good agreement with the corresponding experimental data in the literatures.

  8. Automated NMR fragment based screening identified a novel interface blocker to the LARG/RhoA complex.

    Directory of Open Access Journals (Sweden)

    Jia Gao

    Full Text Available The small GTPase cycles between the inactive GDP form and the activated GTP form, catalyzed by the upstream guanine exchange factors. The modulation of such process by small molecules has been proven to be a fruitful route for therapeutic intervention to prevent the over-activation of the small GTPase. The fragment based approach emerging in the past decade has demonstrated its paramount potential in the discovery of inhibitors targeting such novel and challenging protein-protein interactions. The details regarding the procedure of NMR fragment screening from scratch have been rarely disclosed comprehensively, thus restricts its wider applications. To achieve a consistent screening applicable to a number of targets, we developed a highly automated protocol to cover every aspect of NMR fragment screening as possible, including the construction of small but diverse libray, determination of the aqueous solubility by NMR, grouping compounds with mutual dispersity to a cocktail, and the automated processing and visualization of the ligand based screening spectra. We exemplified our streamlined screening in RhoA alone and the complex of the small GTPase RhoA and its upstream guanine exchange factor LARG. Two hits were confirmed from the primary screening in cocktail and secondary screening over individual hits for LARG/RhoA complex, while one of them was also identified from the screening for RhoA alone. HSQC titration of the two hits over RhoA and LARG alone, respectively, identified one compound binding to RhoA.GDP at a 0.11 mM affinity, and perturbed the residues at the switch II region of RhoA. This hit blocked the formation of the LARG/RhoA complex, validated by the native gel electrophoresis, and the titration of RhoA to ¹⁵N labeled LARG in the absence and presence the compound, respectively. It therefore provides us a starting point toward a more potent inhibitor to RhoA activation catalyzed by LARG.

  9. Allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction

    NARCIS (Netherlands)

    Schaafsma, D.; Gosens, Reinout; Bos, I.S.T.; Meurs, Herman; Zaagsma, Hans; Nelemans, Herman

    2004-01-01

    1 Repeated allergen challenge has been shown to increase the role of Rho-kinase in airway smooth muscle (ASM) contraction. We considered the possibility that active allergic sensitization by itself, that is, without subsequent allergen exposure, could be sufficient to enhance Rho-kinase-mediated ASM

  10. Rho family GTP binding proteins are involved in the regulatory volume decrease process in NIH3T3 mouse fibroblasts

    DEFF Research Database (Denmark)

    Pedersen, Stine F; Beisner, Kristine H; Willumsen, Berthe M

    2002-01-01

    The role of Rho GTPases in the regulatory volume decrease (RVD) process following osmotic cell swelling is controversial and has so far only been investigated for the swelling-activated Cl- efflux. We investigated the involvement of RhoA in the RVD process in NIH3T3 mouse fibroblasts, using wild......-type cells and three clones expressing constitutively active RhoA (RhoAV14). RhoAV14 expression resulted in an up to fourfold increase in the rate of RVD, measured by large-angle light scattering. The increase in RVD rate correlated with RhoAV14 expression. RVD in wild-type cells was unaffected by the Rho...

  11. Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells.

    Science.gov (United States)

    Zhang, G-Y; Yang, W-H; Chen, Z

    2016-05-01

    We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells. We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells. Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa. STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC.

  12. Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells

    International Nuclear Information System (INIS)

    Lee, Jeeyun; Lee, Inkyoung; Park, Chaehwa; Kang, Won Ki

    2006-01-01

    Lovastatin inhibits a 3-hydroxy 3-methylglutaryl coenzyme A reductase and prevents the synthesis of cholesterol precursors, such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), responsible for important cell signaling in cell proliferation and migration. Recently, the anti-cancer effect of lovastatin has been suggested in various tumor types. In this study, we showed that a low dose lovastatin induced senescence and G1 cell cycle arrest in human prostate cancer cells. Addition of GGPP or mevalonate, but not FPP, prevented the lovastatin-induced G1 phase cell cycle arrest and cell senescence. We found that constitutively active RhoA (caRhoA) reversed lovastatin-induced senescence in caRhoA-transfected PC-3 cells. Thus, we postulate that modulation of RhoA may be critical in lovastatin-induced senescence in PC-3 cells

  13. Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Compagnucci, Claudia; Barresi, Sabina [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Petrini, Stefania [Research Laboratories, Confocal Microscopy Core Facility, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Zanni, Ginevra, E-mail: ginevra.zanni@opbg.net [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy)

    2015-04-03

    Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify a new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.

  14. Inclusive rho0 production in anti pp interactions at 22.4 GeV/c

    International Nuclear Information System (INIS)

    Ermilova, D.I.; Filippova, V.V.; Samojlov, V.V.

    1978-01-01

    Inclusive rho 0 production has been investigated in anti pp reactions at 22.4 GeV/c. The total cross section for rho 0 production is 8.1+-2.0 mb. The average number of rhosup(0') s per event is 0.17+-0.03. The average transverse momentum, as obtained by extrapolation of a simple exponential to the psub(T)sup(2) distribution, is 0.52+-0.12 GeV. The Feynman x and center of mass rapidity distributions show rho 0 to be ''centrally'' produced

  15. Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian diaphanous-related Formin mDia1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Aaron D DeWard

    Full Text Available Myelodysplastic syndrome (MDS is characterized by ineffective hematopoiesis and hyperplastic bone marrow. Complete loss or interstitial deletions of the long arm of chromosome 5 occur frequently in MDS. One candidate tumor suppressor on 5q is the mammalian Diaphanous (mDia-related formin mDia1, encoded by DIAPH1 (5q31.3. mDia-family formins act as effectors for Rho-family small GTP-binding proteins including RhoB, which has also been shown to possess tumor suppressor activity. Mice lacking the Drf1 gene that encodes mDia1 develop age-dependent myelodysplastic features. We crossed mDia1 and RhoB knockout mice to test whether the additional loss of RhoB expression would compound the myelodysplastic phenotype. Drf1(-/-RhoB(-/- mice are fertile and develop normally. Relative to age-matched Drf1(-/-RhoB(+/- mice, the age of myelodysplasia onset was earlier in Drf1(-/-RhoB(-/- animals--including abnormally shaped erythrocytes, splenomegaly, and extramedullary hematopoiesis. In addition, we observed a statistically significant increase in the number of activated monocytes/macrophages in both the spleen and bone marrow of Drf1(-/-RhoB(-/- mice relative to Drf1(-/-RhoB(+/- mice. These data suggest a role for RhoB-regulated mDia1 in the regulation of hematopoietic progenitor cells.

  16. Size distribution, chemical composition and oxidation reactivity of particulate matter from gasoline direct injection (GDI) engine fueled with ethanol-gasoline fuel

    International Nuclear Information System (INIS)

    Luo, Yueqi; Zhu, Lei; Fang, Junhua; Zhuang, Zhuyue; Guan, Chun; Xia, Chen; Xie, Xiaomin; Huang, Zhen

    2015-01-01

    Ethanol-gasoline blended fuels have been widely applied in markets recently, as ethanol reduces life-cycle greenhouse gas emissions and improves anti-knock performance. However, its effects on particulate matter (PM) emissions from gasoline direct injection (GDI) engine still need further investigation. In this study, the effects of ethanol-gasoline blended fuels on particle size distributions, number concentrations, chemical composition and soot oxidation activity of GDI engine were investigated. It was found that ethanol-gasoline blended fuels increased the particle number concentration in low-load operating conditions. In higher load conditions, the ethanol-gasoline was effective for reducing the particle number concentration, indicating that the chemical benefits of ethanol become dominant, which could reduce soot precursors such as large n-alkanes and aromatics in gasoline. The volatile organic mass fraction in ethanol-gasoline particulates matter was higher than that in gasoline particulate matter because ethanol reduced the amount of soot precursors during combustion and thereby reduced the elemental carbon proportions in PM. Ethanol addition also increased the proportion of small particles, which confirmed the effects of ethanol on organic composition. Ethanol-gasoline reduced the concentrations of most PAH species, except those with small aromatic rings, e.g., naphthalene. Soot from ethanol-gasoline has lower activation energy of oxidation than that from gasoline. The results in this study indicate that ethanol-gasoline has positive effects on PM emissions control, as the soot oxidation activity is improved and the particle number concentrations are reduced at moderate and high engine loads. - Highlights: • Ethanol-gasoline reduces elemental carbon in PM. • Ethanol-gasoline increases volatile organic fraction in PM. • Soot generated from ethanol-gasoline has higher oxidation activity.

  17. RhoE interferes with Rb inactivation and regulates the proliferation and survival of the U87 human glioblastoma cell line

    International Nuclear Information System (INIS)

    Poch, Enric; Minambres, Rebeca; Mocholi, Enric; Ivorra, Carmen; Perez-Arago, Amparo; Guerri, Consuelo; Perez-Roger, Ignacio; Guasch, Rosa M.

    2007-01-01

    Rho GTPases are important regulators of actin cytoskeleton, but they are also involved in cell proliferation, transformation and oncogenesis. One of this proteins, RhoE, inhibits cell proliferation, however the mechanism that regulates this effect remains poorly understood. Therefore, we undertook the present study to determine the role of RhoE in the regulation of cell proliferation. For this purpose we generated an adenovirus system to overexpress RhoE in U87 glioblastoma cells. Our results show that RhoE disrupts actin cytoskeleton organization and inhibits U87 glioblastoma cell proliferation. Importantly, RhoE expressing cells show a reduction in Rb phosphorylation and in cyclin D1 expression. Furthermore, RhoE inhibits ERK activation following serum stimulation of quiescent cells. Based in these findings, we propose that RhoE inhibits ERK activation, thereby decreasing cyclin D1 expression and leading to a reduction in Rb inactivation, and that this mechanism is involved in the RhoE-induced cell growth inhibition. Moreover, we also demonstrate that RhoE induces apoptosis in U87 cells and also in colon carcinoma and melanoma cells. These results indicate that RhoE plays an important role in the regulation of cell proliferation and survival, and suggest that this protein may be considered as an oncosupressor since it is capable to induce apoptosis in several tumor cell lines

  18. Foci of cyclin A2 interact with actin and RhoA in mitosis.

    Science.gov (United States)

    Loukil, Abdelhalim; Izard, Fanny; Georgieva, Mariya; Mashayekhan, Shaereh; Blanchard, Jean-Marie; Parmeggiani, Andrea; Peter, Marion

    2016-06-09

    Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis depends primarily on the ubiquitin-proteasome system (UPS), while autophagy also contributes. However, a fraction of cyclin A2 persists beyond metaphase. In this work, we focus on cyclin A2-rich foci detected in mitosis by high resolution imaging and analyse their movements. We demonstrate that cyclin A2 interacts with actin and RhoA during mitosis, and that cyclin A2 depletion induces a dramatic decrease in active RhoA in mitosis. Our data suggest cyclin A2 participation in RhoA activation in late mitosis.

  19. Rho0 Photoproduction in Ultra-Peripheral Relativistic Heavy Ion Collisions with STAR

    Energy Technology Data Exchange (ETDEWEB)

    STAR Coll

    2007-12-20

    Photoproduction reactions occur when the electromagnetic field of a relativistic heavy ion interacts with another heavy ion. The STAR collaboration presents a measurement of {rho}{sup 0} and direct {pi}{sup +}{pi}{sup -} photoproduction in ultra-peripheral relativistic heavy ion collisions at {radical}s{sub NN} = 200 GeV. We observe both exclusive photoproduction and photoproduction accompanied by mutual Coulomb excitation. We find a coherent cross-section of {sigma}(AuAu {yields} Au*Au* {rho}{sup 0}) = 530 {+-} 19 (stat.) {+-} 57 (syst.) mb, in accord with theoretical calculations based on a Glauber approach, but considerably below the predictions of a color dipole model. The {rho}{sup 0} transverse momentum spectrum (p{sub T}{sup 2}) is fit by a double exponential curve including both coherent and incoherent coupling to the target nucleus; we find {sigma}{sub inc}/{sigma}{sub coh} = 0.29 {+-} 0.03 (stat.) {+-} 0.08 (syst.). The ratio of direct {pi}{sup +}{pi}{sup -} production is comparable to that observed in {gamma}p collisions at HERA, and appears to be independent of photon energy. Finally, the measured {rho}{sup 0} spin helicity matrix elements agree within errors with the expected s-channel helicity conservation.

  20. Exclusive {rho}{sup 0} production in deep inelastic scattering at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Chekanov, S.; Derrick, M.; Magill, S. [Argonne National Laboratory, Argonne, IL (US)] (and others)

    2007-08-15

    Exclusive {rho}{sup 0} electroproduction at HERA has been studied with the ZEUS detector using 120 pb{sup -1} of integrated luminosity collected during 1996-2000. The analysis was carried out in the kinematic range of photon virtuality 2rho}{sup 0}p cross section and the distribution of the squared-four-momentum transfer to the proton. The helicity analysis of the decay-matrix elements of the {rho}{sup 0} was used to study the ratio of the {gamma}{sup *}p cross section for longitudinal and transverse photon as a function of Q{sup 2} and W. Finally, an effective Pomeron trajectory was extracted. The results are compared to various theoretical predictions. (orig.)

  1. A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects.

    Directory of Open Access Journals (Sweden)

    Katherine Stewart

    2016-02-01

    Full Text Available Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase-activating proteins (GAPs, including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease.

  2. Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1

    DEFF Research Database (Denmark)

    Huelsenbeck, Stefanie C; Roggenkamp, Dennis; May, Martin

    2013-01-01

    B expression, based on the inactivation of Rho/Ras proteins. In this study, we report on a long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. The observations of this study highlight a new pathway involving Rac1...... without any signs of cell death. In conclusion, the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivating Rho/Ras proteins but also by the Rac1-activating toxin CNF1....

  3. Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors.

    Science.gov (United States)

    Olson, Michael F

    2018-05-04

    The 20 members of the Rho GTPase family are key regulators of a wide-variety of biological activities. In response to activation, they signal via downstream effector proteins to induce dynamic alterations in the organization of the actomyosin cytoskeleton. In this review, post-translational modifications, mechanisms of dysregulation identified in human pathological conditions, and the ways that Rho GTPases might be targeted for chemotherapy will be discussed.

  4. On $rho$-dilations of commuting operators

    Czech Academy of Sciences Publication Activity Database

    Müller, Vladimír

    2017-01-01

    Roč. 78, č. 1 (2017), s. 3-20 ISSN 0379-4024 R&D Projects: GA ČR(CZ) GA14-07880S Institutional support: RVO:67985840 Keywords : regular unitary dilation * rho-dilation Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.524, year: 2016 http://www.mathjournals.org/jot/2017-078-001/2017-078-001-001. html

  5. Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages.

    Science.gov (United States)

    Kim, Jun Sub; Kim, Jae Gyu; Jeon, Chan Young; Won, Ha Young; Moon, Mi Young; Seo, Ji Yeon; Kim, Jong Il; Kim, Jaebong; Lee, Jae Yong; Choi, Soo Young; Park, Jinseu; Yoon Park, Jung Han; Ha, Kwon Soo; Kim, Pyeung Hyeun; Park, Jae Bong

    2005-12-31

    Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47(PHOX). Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47(PHOX) may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide.

  6. Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats.

    Science.gov (United States)

    Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

    2015-03-03

    Depression is one of the most common psychiatric disorders in the world; however, its mechanisms remain unclear. Recently, a new signal-transduction pathway, namely Rho/Rho-kinase signalling, has been suggested to be involved in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However there is no evidence showing the involvement of Rho-kinase pathway in depression. In addition, the infralimbic cortex, rodent equivalent to subgenual cingulate cortex has been shown to be responsible for emotional responses. Thus, in the present study, intracranial guide cannulae were stereotaxically implanted bilaterally into the infralimbic cortex, and the effects of repeated microinjections of a Rho-kinase (ROCK) inhibitor Y-27632 (10 nmol) were investigated in rats. Y-27632 significantly decreased immobility time and increased swimming and climbing behaviors when compared to fluoxetine (10 μg) and saline groups in the forced swim test. In addition, Y-27632 treatment did not affect spontaneous locomotor activity and forelimb use in the open-field and cylinder tests respectively; but it enhanced limb placing accuracy in the ladder rung walking test. Our results suggest that Y-27632 could be a potentially active antidepressant agent. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  8. T1rho MRI of menisci and cartilage in patients with osteoarthritis at 3T

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ligong, E-mail: ligong.wang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Chang, Gregory, E-mail: gregory.chang@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Xu, Jian, E-mail: jian.xu.sz@siemens.com [Siemens HealthCare, New York, NY (United States); Vieira, Renata L.R., E-mail: Renata.Vieira@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States); Krasnokutsky, Svetlana, E-mail: Svetlana.Krasnokutsky@nyumc.org [Division of Rheumatology, New York University Langone Medical Center, New York, NY (United States); Abramson, Steven, E-mail: StevenB.Abramson@nyumc.org [Division of Rheumatology, New York University Langone Medical Center, New York, NY (United States); Regatte, Ravinder R., E-mail: Ravinder.Regatte@nyumc.org [Quantitative Multinuclear Musculoskeletal Imaging Group (QMMIG), Center for Biomedical Imaging, Department of Radiology, New York University Langone Medical Center, New York, NY (United States)

    2012-09-15

    Objective: To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren–Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. Materials and methods: 30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. Results: Lateral (72 ± 10 ms, median ± interquartile range) and medial (65 ± 10 ms) femoral anterior cartilage subregions in moderate–severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful–minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate–severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful–minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal). Conclusion: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with

  9. Diabetes and overexpression of proNGF cause retinal neurodegeneration via activation of RhoA pathway.

    Directory of Open Access Journals (Sweden)

    Mohammed M H Al-Gayyar

    Full Text Available Our previous studies showed positive correlation between accumulation of proNGF, activation of RhoA and neuronal death in diabetic models. Here, we examined the neuroprotective effects of selective inhibition of RhoA kinase in the diabetic rat retina and in a model that stably overexpressed the cleavage-resistance proNGF plasmid in the retina. Male Sprague-Dawley rats were rendered diabetic using streptozotocin or stably express cleavage-resistant proNGF plasmid. The neuroprotective effects of the intravitreal injection of RhoA kinase inhibitor Y27632 were examined in vivo. Effects of proNGF were examined in freshly isolated primary retinal ganglion cell (RGC cultures and RGC-5 cell line. Retinal neurodegeneration was assessed by counting TUNEL-positive and Brn-3a positive retinal ganglion cells. Expression of proNGF, p75(NTR, cleaved-PARP, caspase-3 and p38MAPK/JNK were examined by Western-blot. Activation of RhoA was assessed by pull-down assay and G-LISA. Diabetes and overexpression of proNGF resulted in retinal neurodegeneration as indicated by 9- and 6-fold increase in TUNEL-positive cells, respectively. In vitro, proNGF induced 5-fold cell death in RGC-5 cell line, and it induced >10-fold cell death in primary RGC cultures. These effects were associated with significant upregulation of p75(NTR and activation of RhoA. While proNGF induced TNF-α expression in vivo, it selectively activated RhoA in primary RGC cultures and RGC-5 cell line. Inhibiting RhoA kinase with Y27632 significantly reduced diabetes- and proNGF-induced activation of proapoptotic p38MAPK/JNK, expression of cleaved-PARP and caspase-3 and prevented retinal neurodegeneration in vivo and in vitro. Taken together, these results provide compelling evidence for a causal role of proNGF in diabetes-induced retinal neurodegeneration through enhancing p75(NTR expression and direct activation of RhoA and p38MAPK/JNK apoptotic pathways.

  10. T1rho MRI of menisci and cartilage in patients with osteoarthritis at 3T

    International Nuclear Information System (INIS)

    Wang, Ligong; Chang, Gregory; Xu, Jian; Vieira, Renata L.R.; Krasnokutsky, Svetlana; Abramson, Steven; Regatte, Ravinder R.

    2012-01-01

    Objective: To assess and compare subregional and whole T1rho values (median ± interquartile range) of femorotibial cartilage and menisci in patients with doubtful (Kellgren–Lawrence (KL) grade 1) to severe (KL4) osteoarthritis (OA) at 3T. Materials and methods: 30 subjects with varying degrees of OA (KL1–4, 13 females, 17 males, mean age ± SD = 63.9 ± 13.1 years) were evaluated on a 3T MR scanner using a spin-lock-based 3D GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echo (FSE) images in sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage and meniscus Whole-organ MR imaging score (WORMS) grading. Wilcoxon rank sum test was performed to determine whether there were any statistically significant differences between subregional and whole T1rho values of femorotibial cartilage and menisci in subjects with doubtful to severe OA. Results: Lateral (72 ± 10 ms, median ± interquartile range) and medial (65 ± 10 ms) femoral anterior cartilage subregions in moderate–severe OA subjects had significantly higher T1rho values (P < 0.05) than cartilage subregions and whole femorotibial cartilage in doubtful–minimal OA subjects. There were statistically significant differences in meniscus T1rho values of the medial posterior subregion of subjects with moderate–severe OA and T1rho values of all subregions and the whole meniscus in subjects with doubtful–minimal OA. When evaluated based on WORMS, statistically significant differences were identified in T1rho values between the lateral femoral anterior cartilage subregion in patients with WORMS5–6 (advanced degeneration) and whole femorotibial cartilage and all cartilage subregions in patients with WORMS0–1 (normal). Conclusion: T1rho values are higher in specific meniscus and femorotibial cartilage subregions. These findings suggest that regional damage of both femorotibial hyaline cartilage and menisci may be associated with

  11. Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty infiltration following rotator cuff tears.

    Science.gov (United States)

    Davies, Michael R; Lee, Lawrence; Feeley, Brian T; Kim, Hubert T; Liu, Xuhui

    2017-07-01

    Previous studies have suggested that macrophage-mediated chronic inflammation is involved in the development of rotator cuff muscle atrophy and degeneration following massive tendon tears. Increased RhoA signaling has been reported in chronic muscle degeneration, such as muscular dystrophy. However, the role of RhoA signaling in macrophage infiltration and rotator muscle degeneration remains unknown. Using a previously established rat model of massive rotator cuff tears, we found RhoA signaling is upregulated in rotator cuff muscle following a massive tendon-nerve injury. This increase in RhoA expression is greatly potentiated by the administration of a potent RhoA activator, lysophosphatidic acid (LPA), and is accompanied by increased TNFα and TGF-β1 expression in rotator cuff muscle. Boosting RhoA signaling with LPA significantly worsened rotator cuff muscle atrophy, fibrosis, and fatty infiltration, accompanied with massive monocytic infiltration of rotator cuff muscles. Co-staining of RhoA and the tissue macrophage marker CD68 showed that CD68+ tissue macrophages are the dominant cell source of increased RhoA signaling in rotator cuff muscles after tendon tears. Taken together, our findings suggest that LPA-mediated RhoA signaling in injured muscle worsens the outcomes of atrophy, fibrosis, and fatty infiltration by increasing macrophage infiltraion in rotator cuff muscle. Clinically, inhibiting RhoA signaling may represent a future direction for developing new treatments to improve muscle quality following massive rotator cuff tears. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1539-1547, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  12. Effect of the piston top contour on the tumble flow and combustion features of a GDI engine with a CMCV: a CFD study

    Directory of Open Access Journals (Sweden)

    Congbo Yin

    2016-01-01

    Full Text Available In spite of much progress in the development of gasoline direct injection (GDI engines, choosing an appropriate piston top contour to obtain desirable combustion efficiency is still an arduous process for engineers. This study investigates the combined effects of piston bowl geometry and a charge motion control valve (CMCV on tumble flow and combustion features in GDI engines. Based on the model validation, the processes of intake, spray, mixture formation and combustion at different engine speeds are simulated and analyzed for different piston shapes for the two cases of opening and closing the CMCV. The results show that the bowl on the top of piston is beneficial for the formation and development of tumble flow. The flat top piston with the CMCV closed is able to achieve acceptable combustion pressure. However, with the increase of engine speed and load, the advantages of the flat top pistons gradually disappear; the dual offset bowl piston has a minimum tumble ratio and turbulence kinetic energy (TKE at the end of the compression stroke because of the projection in the middle of the piston top surface which leads to a lower pressure rise rate and a reduced flame propagation speed at high load. The closed CMCV contributes to a faster evaporation rate and a more uniform mixture at lower speeds. It is not recommended for use at high speeds due to lower intake air mass and reduced combustion pressure. The research provides an effective way for engineers to choose an appropriate piston top contour combined with a CMCV to obtain desirable combustion efficiency.

  13. Inclusive photoproduction of rho and ω in the photon energy range 20 to 70 GeV

    International Nuclear Information System (INIS)

    Atkinson, M.; Laberrigue, J.; Levy, J.M.; La Vaissiere, C. de; Yiou, T.P.; Lassalle, J.C.; Patrick, G.N.; Storr, K.M.; Axon, T.J.; Barberis, D.; Brodbeck, T.J.; Brookes, G.R.; Bunn, J.J.; Bussey, P.J.; Clegg, A.B.; Dainton, J.B.; Davenport, M.; Dickinson, B.; Diekmann, B.; Donnachie, A.; Ellison, R.J.; Flower, P.; Hughes-Jones, R.E.; Hutton, J.S.; Ibbotson, M.; Jakob, H.P.; Jung, M.; Kemp, M.A.R.; Kumar, B.R.; Lafferty, G.D.; Lane, J.B.; Liebenau, V.; McClatchey, R.H.; Mercer, D.; Morris, J.A.G.; Morris, J.V.; Newton, D.; Paterson, C.; Paul, E.; Raine, C.; Reidenbach, M.; Rotscheidt, H.; Schloesser, A.; Sharp, P.H.; Skillicorn, I.O.; Smith, K.M.; Thompson, R.J.; Waite, A.P.; Worsell, M.F.

    1984-01-01

    Inclusive production of rho 0 , ω, and rhosup(+-) at low transverse momentum has been measured in γp collisions with photons of energy 20 to 70 GeV. The vector mesons have been studied as functions of the Feynman variable chisub(F), varying between -0.2 and 0.95, i.e. excluding the 'elastic' peaks of rho 0 and ω photoproduction. For chisub(F) 0 ) approx.= sigma (ω) approx.= 1/2[sigma(p + ) + sigma(p - )]. For chisub(F) > 0.6, it is observed that sigma(p 0 ) > sigma(ω) >=1/2[sigma(rho + )+sigma(rho - )] and the differences increase with increasing chisub(F). Over the rhosub(F) range -0.2 0 and ω production. (orig.)

  14. Measurement of the spin density matrix for the $\\rho^0$, $K^{*0}(892)$ and $\\phi$ produced in $Z^0$ Decays

    CERN Document Server

    Abreu, P; Adye, T; Alekseev, G D; Alemany, R; Allport, P P; Almehed, S; Amaldi, Ugo; Amato, S; Andersson, P; Andreazza, A; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barbi, M S; Barbiellini, Guido; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Bärring, O; Bates, M J; Battaglia, Marco; Baubillier, M; Baudot, J; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Billoir, P; Bizouard, M A; Bloch, D; Blume, M; Bonesini, M; Bonivento, W; Booth, P S L; Borgland, A W; Borisov, G; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Bozzo, M; Branchini, P; Brand, K D; Brenke, T; Brenner, R A; Bricman, C; Brown, R C A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Cabrera, S; Caccia, M; Calvi, M; Camacho-Rozas, A J; Camporesi, T; Canale, V; Canepa, M; Cao, F; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Chapkin, M M; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chen, M; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cindro, V; Collins, P; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Dahm, J; D'Almagne, B; Dam, M; Damgaard, G; Dauncey, P D; Davenport, Martyn; Da Silva, W; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Brabandere, S; De Clercq, C; La Vaissière, C de; De Lotto, B; De Min, A; De Paula, L S; Dijkstra, H; Di Ciaccio, Lucia; Di Diodato, A; Djannati, A; Dolbeau, J; Doroba, K; Dracos, M; Drees, J; Drees, K A; Dris, M; Durand, J D; Edsall, D M; Ehret, R; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fanourakis, G K; Fassouliotis, D; Feindt, Michael; Fenyuk, A; Ferrari, P; Ferrer, A; Fichet, S; Filippas-Tassos, A; Firestone, A; Fischer, P A; Föth, H; Fokitis, E; Fontanelli, F; Formenti, F; Franek, B J; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gandelman, M; García, C; García, J; Gaspar, C; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerber, J P; Gerdyukov, L N; Gokieli, R; Golob, B; Gonçalves, P; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Graziani, E; Green, C; Grefrath, A; Gris, P; Grosdidier, G; Grzelak, K; Günther, M; Guy, J; Hahn, F; Hahn, S; Hajduk, Z; Hallgren, A; Hamacher, K; Harris, F J; Hedberg, V; Henriques, R P; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Heuser, J M; Higón, E; Holmgren, S O; Holt, P J; Holthuizen, D J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, L B; Jönsson, P E; Joram, Christian; Juillot, P; Kaiser, M; Kapusta, F; Karafasoulis, K; Katsanevas, S; Katsoufis, E C; Keränen, R; Khokhlov, Yu A; Khomenko, B A; Khovanskii, N N; King, B J; Kjaer, N J; Klapp, O; Klein, H; Kluit, P M; Knoblauch, D; Kokkinias, P; Koratzinos, M; Korcyl, K; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kreuter, C; Kronkvist, I J; Krstic, J; Krumshtein, Z; Krupinski, W; Kubinec, P; Kucewicz, W; Kurvinen, K L; Lacasta, C; Laktineh, I; Lamsa, J; Lanceri, L; Lane, D W; Langefeld, P; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Legan, C K; Leisos, A; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Libby, J; Liko, D; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Maehlum, G; Mahon, J R; Maio, A; Malmgren, T G M; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Masik, J; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; McPherson, G; Medbo, J; Meroni, C; Meyer, S; Meyer, W T; Myagkov, A; Michelotto, M; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Møller, R; Mönig, K; Monge, M R; Morettini, P; Müller, H; Münich, K; Mulders, M; Mundim, L M; Murray, W J; Muryn, B; Myatt, Gerald; Myklebust, T; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neumann, W; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nieuwenhuizen, M; Nikolaenko, V; Nikolenko, M; Niss, P; Nomerotski, A; Normand, Ainsley; Nygren, A; Oberschulte-Beckmann, W; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Orazi, G; Österberg, K; Ouraou, A; Paganini, P; Paganoni, M; Pain, R; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Pegoraro, M; Peralta, L; Pernegger, H; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Piana, G; Pierre, F; Pimenta, M; Podobnik, T; Podobrin, O; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Ratoff, P N; Read, A L; Reale, M; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Reinhardt, R; Renton, P B; Resvanis, L K; Richard, F; Rídky, J; Rinaudo, G; Røhne, O M; Romero, A; Ronchese, P; Roos, L; Rosenberg, E I; Rosinsky, P; Roudeau, Patrick; Rovelli, T; Ruhlmann-Kleider, V; Ruiz, A; Rybicki, K; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sannino, M; Schneider, H; Schwickerath, U; Schyns, M A E; Sciolla, G; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Seitz, A; Sekulin, R L; Serbelloni, L; Shellard, R C; Sheridan, A; Siegrist, P; Silvestre, R; Simonetto, F; Sissakian, A N; Skaali, T B; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sokolov, A; Solovyanov, O; Sosnowski, R; Souza-Santos, D; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stampfer, D; Stanescu, C; Stanic, S; Stapnes, Steinar; Stavitski, I; Stevenson, K; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tavernet, J P; Tegenfeldt, F; Terranova, F; Thomas, J; Tilquin, A; Timmermans, J; Tkatchev, L G; Todorov, T; Todorova, S; Toet, D Z; Tomaradze, A G; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Tristram, G; Trombini, A; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tyndel, M; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; van Apeldoorn, G W; van Dam, P; Van Eldik, J; Van Lysebetten, A; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Vilanova, D; Vincent, P; Vitale, L; Vlasov, E; Vodopyanov, A S; Vrba, V; Wahlen, H; Walck, C; Weiser, C; Wetherell, Alan M; Wicke, D; Wickens, J H; Wielers, M; Wilkinson, G R; Williams, W S C; Winter, M; Witek, M; Wlodek, T; Yi, J; Yip, K; Yushchenko, O P; Zach, F; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zucchelli, G C; Zumerle, G

    1997-01-01

    The spin density matrix elements for the $\\rho^0$, K$^{*0}(892)$ and $\\phi$ produced in hadronic Z$^0$ decays are measured in the DELPHI detector. There is no evidence for spin alignment of the K$^{*0}(892)$ and $\\phi$ in the region $x_p \\leq 0.3$ ($x_p = p/p_{beam}$), where $\\rho_{00} = 0.33 \\pm 0.05$ and $\\rho_{00} = 0.30 \\pm 0.04$, respectively. In the fragmentation region, $x_p \\geq 0.4$, there is some indication for spin alignment of the $\\rho^0$ and K$^{*0}(892)$, since $\\rho_{00} = 0.43 \\pm 0.05$ and $\\rho_{00} = 0.46 \\pm 0.08$, respectively. These values are compared with those found in meson-induced hadronic reactions. For the $\\phi$, $\\rho_{00} = 0.30 \\pm 0.04$ for $x_p \\geq 0.4$ and $0.55 \\pm 0.10$ for $x_p \\geq 0.7$. The off-diagonal spin density matrix element $\\rho_{1-1}$ is consistent with zero in all cases.

  15. Measurement of Branching Fractions and CP-Violating Asymmetries in B -> rho+/-h-/+

    CERN Document Server

    Höcker, A

    2003-01-01

    We present measurements of branching fractions and CP-violating asymmetries in B sup 0 -> rho sup+- pi sup+- and B sup 0 -> rho sup - K sup + decays. The results are obtained from a data sample of 88.9 x 10 sup 6 UPSILON(4S) -> B(bar B) decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. From a time-dependent maximum likelihood fit we measure the charge-averaged branching fractions BETA(B sup 0 -> rho sup+- pi sup+-) = (22.6 +- 1.8 (stat) +- 2.2 (syst)) x 10 sup - sup 6 and BETA(B sup 0 -> rho sup - K sup +) = (7.3 sub - sub 1 sub . sub 2 sup + sup 1 sup . sup 3 +- 1.3) x 10 sup - sup 6; and the CP-violating charge asymmetries A sub C sub P suprho suppi = -0.18 +- 0.08 +- 0.03 and A sub C sub P suprho sup K = 0.28 +- 0.17 +- 0.08; the direct CP violation parameter C subrho subpi = 0.36 +- 0.18 +- 0.04 and the mixing-induced CP violation parameter S subrho subpi = 0.19 +- 0.24 +- 0.03; and the dilution parameters DELTA C subrho subpi = 0.28 sub - sub 0 sub . sub 1 sub 9 ...

  16. PHASE-RESOLVED TIMING ANALYSIS OF GRS 1915+105 IN ITS {rho} STATE

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Shu-Ping; Wang, Na; Ding, Guo-Qiang [Xinjiang Astronomical Observatory, Chinese Academy of Sciences, 150 Science 1-Street, Urumqi, Xinjiang 830011 (China); Qu, Jin-Lu, E-mail: yanshup@xao.ac.cn, E-mail: na.wang@xao.ac.cn [Key Laboratory for Particle Astrophysics, Institute of High Energy Physics, Chinese Academy of Sciences, 19B Yuquan Road, Beijing 100049 (China)

    2013-04-10

    We made a phase-resolved timing analysis of GRS 1915+105 in its {rho} state and obtained detailed {rho} cycle evolutions of the frequency, amplitude, and coherence of the low-frequency quasi-periodic oscillation (LFQPO). We combined our timing results with the spectral study by Neilsen et al. to perform an elaborate comparison analysis. Our analyses show that the LFQPO frequency does not scale with the inner disk radius, but it is related to the spectral index, indicating a possible correlation between the LFQPO and the corona. The LFQPO amplitude spectrum and other results are naturally explained by tying the LFQPO to the corona. The similarities of the spectra of variability parameters between the LFQPOs from {rho} state and those from more steady states indicate that the LFQPOs of GRS 1915+105 in very different states seem to share the same origin.

  17. RhoA/Rho kinase signaling regulates transforming growth factor-β1-induced chondrogenesis and actin organization of synovium-derived mesenchymal stem cells through interaction with the Smad pathway.

    Science.gov (United States)

    Xu, Ting; Wu, Mengjie; Feng, Jianying; Lin, Xinping; Gu, Zhiyuan

    2012-11-01

    Recent studies have suggested that synovium-derived mesenchymal stem cells (SMSCs) may be promising candidates for tissue engineering and play an important role in cartilage regeneration. However, the mechanisms of SMSC chondrogenesis remain to be identified and characterized. The aim of this study was to evaluate the activation of the RhoA/Rho kinase (ROCK) pathway, as well as the manner by which it may contribute to chondrogenesis and the actin cytoskeletal organization of rat temporomandibular SMSCs in response to transforming growth factor-β1 (TGF-β1). Primary isolated SMSCs were treated with TGF-β1, and their actin organization was examined by fluorescein isothiocyanate-phalloidin staining. The specific biochemical inhibitors, C3 transferase, Y27632 and SB431542, were employed to evaluate the function of RhoA/ROCK and Smads. The effect of C3 transferase and Y27632 on the gene expression of chondrocyte-specific markers was evaluated by quantitative real-time polymerase chain reaction. To examine the effect of Y27632 on Smad2/3 phosphorylation induced by TGF-β1, western blot analysis was also performed. The stimulation of TGF-β1 in SMSCs resulted in the activation of the RhoA/ROCK pathway and concomitantly induced cytoskeletal reorganization, which was specifically blocked by C3 transferase and Y27632. The TGF-β-induced gene expression of Sox9, type I collagen, type II collagen and aggrecan was also inhibited by both C3 transferase and Y27632, at different levels. Y27632 treatment reduced the phosphorylation of Smad2/3 in a concentration-dependent manner. These results demonstrate the RhoA/ROCK activation regulates chondrocyte-specific gene transcription and cytoskeletal organization induced by TGF-β1 by interacting with the Smad pathway. This may have significant implications for the successful utilization of SMSCs as a cell source for articular cartilage tissue engineering.

  18. RhoA, Rac1 and Cdc42 differentially regulate aSMA and collagen I expression in mesenchymal stem cells.

    Science.gov (United States)

    Ge, Jianfeng; Burnier, Laurent; Adamopoulou, Maria; Kwa, Mei Qi; Schaks, Matthias; Rottner, Klemens; Brakebusch, Cord

    2018-04-26

    Mesenchymal stem cells (MSC) are suggested to be important progenitors of myofibroblasts in fibrosis. To understand the role of Rho GTPase signaling in TGFβ-induced myofibroblast differentiation of MSC, we generated a novel MSC line and descendants of it lacking functional Rho GTPases and Rho GTPase signaling components. Unexpectedly, our data revealed that Rho GTPase signaling is required for TGFβ-induced expression of αSMA, but not of collagen I α1 (col1a1). While loss of RhoA and Cdc42 reduced αSMA expression, ablation of the Rac1 gene had the opposite effect. Although actin polymerization and MRTFa were crucial for TGFβ-induced αSMA expression, neither Arp2/3 dependent actin polymerization nor cofilin dependent severing and depolymerization of F-actin were required. Instead, F-actin levels were dependent on cell contraction and TGFβ-induced actin polymerisation correlated with increased cell contraction mediated by RhoA and Cdc42. Finally, we observed impaired collagen I secretion in MSC lacking RhoA or Cdc42. These data give novel molecular insights into the role of Rho GTPases in TGFβ signaling and have implications for our understanding of MSC function in fibrosis. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Hougaard, Charlotte; Hoffmann, Else K

    2006-01-01

    swollen cells, this reduction was prevented by cholesterol depletion, which also increased isotonic Rho activity. Thrombin, which stimulates Rho and causes actin polymerization, potentiated VRAC in modestly swollen cells. VRAC activity was unaffected by inclusion of a water-soluble PtdIns(4,5)P(2......) analogue or a PtdIns(4,5)P(2)-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P(2). It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part......The mechanisms controlling the volume-regulated anion current (VRAC) are incompletely elucidated. Here, we investigate the modulation of VRAC by cellular cholesterol and the potential involvement of F-actin, Rho, Rho kinase, and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P(2...

  20. Identification of potential small molecule binding pockets on Rho family GTPases.

    Directory of Open Access Journals (Sweden)

    Juan Manuel Ortiz-Sanchez

    Full Text Available Rho GTPases are conformational switches that control a wide variety of signaling pathways critical for eukaryotic cell development and proliferation. They represent attractive targets for drug design as their aberrant function and deregulated activity is associated with many human diseases including cancer. Extensive high-resolution structures (>100 and recent mutagenesis studies have laid the foundation for the design of new structure-based chemotherapeutic strategies. Although the inhibition of Rho signaling with drug-like compounds is an active area of current research, very little attention has been devoted to directly inhibiting Rho by targeting potential allosteric non-nucleotide binding sites. By avoiding the nucleotide binding site, compounds may minimize the potential for undesirable off-target interactions with other ubiquitous GTP and ATP binding proteins. Here we describe the application of molecular dynamics simulations, principal component analysis, sequence conservation analysis, and ensemble small-molecule fragment mapping to provide an extensive mapping of potential small-molecule binding pockets on Rho family members. Characterized sites include novel pockets in the vicinity of the conformationaly responsive switch regions as well as distal sites that appear to be related to the conformations of the nucleotide binding region. Furthermore the use of accelerated molecular dynamics simulation, an advanced sampling method that extends the accessible time-scale of conventional simulations, is found to enhance the characterization of novel binding sites when conformational changes are important for the protein mechanism.

  1. RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Hoban PR

    2006-06-01

    Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression. Methods Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies. Results Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p Conclusion These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation.

  2. Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats.

    Science.gov (United States)

    Shiotani, Satoko; Shimada, Mitsuo; Suehiro, Taketoshi; Soejima, Yuji; Yosizumi, Tomoharu; Shimokawa, Hiroaki; Maehara, Yoshihiko

    2004-08-15

    Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.

  3. Rho A Regulates Epidermal Growth Factor-Induced Human Osteosarcoma MG63 Cell Migration

    Directory of Open Access Journals (Sweden)

    Jinyang Wang

    2018-05-01

    Full Text Available Osteosarcoma, the most common primary bone tumor, occurs most frequently in children and adolescents and has a 5-year survival rate, which is unsatisfactory. As epidermal growth factor receptor (EGFR positively correlates with TNM (tumor-node-metastasis stage in osteosarcoma, EGFR may play an important role in its progression. The purpose of this study was to explore potential mechanisms underlying this correlation. We found that EGF promotes MG63 cell migration and invasion as well as stress fiber formation via Rho A activation and that these effects can be reversed by inhibiting Rho A expression. In addition, molecules downstream of Rho A, including ROCK1, LIMK2, and Cofilin, are activated by EGF in MG63 cells, leading to actin stress fiber formation and cell migration. Moreover, inhibition of ROCK1, LIMK2, or Cofilin in MG63 cells using known inhibitors or short hairpin RNA (shRNA prevents actin stress fiber formation and cell migration. Thus, we conclude that Rho A/ROCK1/LIMK2/Cofilin signaling mediates actin microfilament formation in MG63 cells upon EGFR activation. This novel pathway provides a promising target for preventing osteosarcoma progression and for treating this cancer.

  4. Role of the Small GTPase Rho3 in Golgi/Endosome trafficking through functional interaction with adaptin in Fission Yeast.

    Directory of Open Access Journals (Sweden)

    Ayako Kita

    Full Text Available BACKGROUND: We had previously identified the mutant allele of apm1(+ that encodes a homolog of the mammalian µ1A subunit of the clathrin-associated adaptor protein-1 (AP-1 complex, and we demonstrated the role of Apm1 in Golgi/endosome trafficking, secretion, and vacuole fusion in fission yeast. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we isolated rho3(+, which encodes a Rho-family small GTPase, an important regulator of exocystosis, as a multicopy-suppressor of the temperature-sensitive growth of the apm1-1 mutant cells. Overexpression of Rho3 suppressed the Cl(- sensitivity and immunosuppressant sensitivity of the apm1-1 mutant cells. Overexpression of Rho3 also suppressed the fragmentation of vacuoles, and the accumulation of v-SNARE Syb1 in Golgi/endosomes and partially suppressed the defective secretion associated with apm1-deletion cells. Notably, electron microscopic observation of the rho3-deletion cells revealed the accumulation of abnormal Golgi-like structures, vacuole fragmentation, and accumulation of secretory vesicles; these phenotypes were very similar to those of the apm1-deletion cells. Furthermore, the rho3-deletion cells and apm1-deletion cells showed very similar phenotypic characteristics, including the sensitivity to the immunosuppressant FK506, the cell wall-damaging agent micafungin, Cl(-, and valproic acid. Green fluorescent protein (GFP-Rho3 was localized at Golgi/endosomes as well as the plasma membrane and division site. Finally, Rho3 was shown to form a complex with Apm1 as well as with other subunits of the clathrin-associated AP-1 complex in a GTP- and effector domain-dependent manner. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings reveal a novel role of Rho3 in the regulation of Golgi/endosome trafficking and suggest that clathrin-associated adaptor protein-1 and Rho3 co-ordinate in intracellular transport in fission yeast. To the best of our knowledge, this study provides the first evidence

  5. Cdc42 and RhoA reveal different spatio-temporal dynamics upon local stimulation with Semaphorin-3A

    Directory of Open Access Journals (Sweden)

    Federico eIseppon

    2015-08-01

    Full Text Available Small RhoGTPases, such as Cdc42 and RhoA, are key players in integrating external cues and intracellular signaling pathways that regulate growth cone (GC motility. Indeed, Cdc42 is involved in actin polymerization and filopodia formation, whereas RhoA induces GC collapse and neurite retraction through actomyosin contraction. In this study we employed Förster Resonance Energy Transfer (FRET microscopy to study the spatio-temporal dynamics of Cdc42 and RhoA in GCs in response to local Semaphorin-3A stimulation obtained with lipid vesicles filled with Semaphorin-3A and positioned near the selected GC using optical tweezers. We found that Cdc42 and RhoA were activated at the leading edge of NG108-15 neuroblastoma cells during spontaneous cycles of protrusion and retraction, respectively. The release of Semaphorin-3A brought to a progressive activation of RhoA within 30 seconds from the stimulus in the central region of the GC that collapsed and retracted. In contrast, the same stimulation evoked waves of Cdc42 activation propagating away from the stimulated region. A more localized stimulation obtained with Sema3A coated beads placed on the GC, led to Cdc42 active waves that propagated in a retrograde manner with a mean period of 70 seconds, and followed by GC retraction. Therefore, Semaphorin-3A activates both Cdc42 and RhoA with a complex and different spatial-temporal dynamics.

  6. ROCK and RHO Playlist for Preimplantation Development: Streaming to HIPPO Pathway and Apicobasal Polarity in the First Cell Differentiation.

    Science.gov (United States)

    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.

  7. Induction of human microsomal prostaglandin E synthase 1 by activated oncogene RhoA GTPase in A549 human epithelial cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hye Jin [Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Lee, Dong-Hyung [Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Busan (Korea, Republic of); Park, Seong-Hwan; Kim, Juil; Do, Kee Hun [Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); An, Tae Jin; Ahn, Young Sup; Park, Chung Berm [Department of Herbal Crop Research, NIHHS, RDA, Eumseong (Korea, Republic of); Moon, Yuseok, E-mail: moon@pnu.edu [Laboratory of Systems Mucosal Biomodulation, Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Medical Research Institute and Research Institute for Basic Sciences, Pusan National University, Busan (Korea, Republic of)

    2011-09-30

    Highlights: {yields} As a target of oncogene RhoA-linked signal, a prostaglandin metabolism is assessed. {yields} RhoA activation increases PGE{sub 2} levels and its metabolic enzyme mPGES-1. {yields} RhoA-activated NF-{kappa}B and EGR-1 are positively involved in mPGES-1 induction. -- Abstract: Oncogenic RhoA GTPase has been investigated as a mediator of pro-inflammatory responses and aggressive carcinogenesis. Among the various targets of RhoA-linked signals, pro-inflammatory prostaglandin E{sub 2} (PGE{sub 2}), a major prostaglandin metabolite, was assessed in epithelial cancer cells. RhoA activation increased PGE{sub 2} levels and gene expression of the rate-limiting PGE{sub 2} producing enzymes, cyclooxygenase-2 and microsomal prostaglandin E synthase 1 (mPGES-1). In particular, human mPGES-1 was induced by RhoA via transcriptional activation in control and interleukin (IL)-1{beta}-activated cancer cells. To address the involvement of potent signaling pathways in RhoA-activated mPGES-1 induction, various signaling inhibitors were screened for their effects on mPGES-1 promoter activity. RhoA activation enhanced basal and IL-1{beta}-mediated phosphorylated nuclear factor-{kappa}B and extracellular signal-regulated kinase1/2 proteins, all of which were positively involved in RhoA-induced gene expression of mPGES-1. As one potent down-stream transcription factor of ERK1/2 signals, early growth response gene 1 product also mediated RhoA-induced gene expression of mPGES-1 by enhancing transcriptional activity. Since oncogene-triggered PGE{sub 2} production is a critical modulator of epithelial tumor cells, RhoA-associated mPGES-1 represents a promising chemo-preventive or therapeutic target for epithelial inflammation and its associated cancers.

  8. A Salmonella typhimurium-translocated Glycerophospholipid:Cholesterol Acyltransferase Promotes Virulence by Binding to the RhoA Protein Switch Regions

    Energy Technology Data Exchange (ETDEWEB)

    LaRock, Doris L.; Brzovic, Peter S.; Levin, Itay; Blanc, Marie-Pierre; Miller, Samuel I.

    2012-08-24

    Salmonella enterica serovar typhimurium translocates a glycerophospholipid: cholesterol acyltransferase (SseJ) into the host cytosol after its entry into mammalian cells. SseJ is recruited to the cytoplasmic face of the host cell phagosome membrane where it is activated upon binding the small GTPase, RhoA. SseJ is regulated similarly to cognate eukaryotic effectors, as only the GTP-bound form of RhoA family members stimulates enzymatic activity. Using NMR and biochemistry, this work demonstrates that SseJ competes effectively with Rhotekin, ROCK, and PKN1 in binding to a similar RhoA surface. The RhoA surface that binds SseJ includes the regulatory switch regions that control activation of mammalian effectors. These data were used to create RhoA mutants with altered SseJ binding and activation. This structure-function analysis supports a model in which SseJ activation occurs predominantly through binding to residues within switch region II. We further defined the nature of the interaction between SseJ and RhoA by constructing SseJ mutants in the RhoA binding surface. These data indicate that SseJ binding to RhoA is required for recruitment of SseJ to the endosomal network and for full Salmonella virulence for inbred susceptible mice, indicating that regulation of SseJ by small GTPases is an important virulence strategy of this bacterial pathogen. The dependence of a bacterial effector on regulation by a mammalian GTPase defines further how intimately host pathogen interactions have coevolved through similar and divergent evolutionary strategies.

  9. RPO41-independent maintenance of [rho-] mitochondrial DNA in Saccharomyces cerevisiae.

    Science.gov (United States)

    Fangman, W L; Henly, J W; Brewer, B J

    1990-01-01

    A subset of promoters in the mitochondrial DNA (mtDNA) of the yeast Saccharomyces cerevisiae has been proposed to participate in replication initiation, giving rise to a primer through site-specific cleavage of an RNA transcript. To test whether transcription is essential for mtDNA maintenance, we examined two simple mtDNA deletion ([rho-]) genomes in yeast cells. One genome (HS3324) contains a consensus promoter (ATATAAGTA) for the mitochondrial RNA polymerase encoded by the nuclear gene RPO41, and the other genome (4a) does not. As anticipated, in RPO41 cells transcripts from the HS3324 genome were more abundant than were transcripts from the 4a genome. When the RPO41 gene was disrupted, both [rho-] genomes were efficiently maintained. The level of transcripts from HS3324 mtDNA was decreased greater than 400-fold in cells carrying the RPO41 disrupted gene; however, the low-level transcripts from 4a mtDNA were undiminished. These results indicate that replication of [rho-] genomes can be initiated in the absence of wild-type levels of the RPO41-encoded RNA polymerase.

  10. Diffractive Photoproduction of Rho Mesons with Large Momentum Transfer at HERA

    CERN Document Server

    Aktas, A.; Anthonis, T.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Babaev, A.; Backovic, S.; Baghdasaryan, A.; Baranov, P.; Barrelet, E.; Bartel, W.; Baudrand, S.; Baumgartner, S.; Becker, J.; Beckingham, M.; Behnke, O.; Behrendt, O.; Belousov, A.; Berger, N.; Bizot, J.C.; Boenig, M.-O.; Boudry, V.; Bracinik, J.; Brandt, G.; Brisson, V.; Bruncko, D.; Busser, F.W.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Contreras, J.G.; Coughlan, J.A.; Cox, B.E.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Dau, W.D.; Daum, K.; de Boer, Y.; Delcourt, B.; Del Degan, M.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dubak, A.; Eckerlin, Guenter; Efremenko, V.; Egli, S.; Eichler, R.; Eisele, F.; Eliseev, A.; Elsen, E.; Essenov, S.; Falkewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Finke, L.; Fleischer, M.; Fleischmann, P.; Flucke, G.; Fomenko, A.; Franke, G.; Frisson, T.; Gabathuler, E.; Garutti, E.; Gayler, J.; Gerlich, C.; Ghazaryan, Samvel; Ginzburgskaya, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Goettlich, M.; Gogitidze, N.; Gorbounov, S.; Grab, C.; Greenshaw, T.; Gregori, M.; Grell, B.R.; Grindhammer, G.; Gwilliam, C.; Haidt, D.; Hajduk, L.; Hansson, M.; Heinzelmann, G.; Henderson, R.C.W.; Henschel, H.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hovhannisyan, A.; Hreus, T.; Hussain, S.; Ibbotson, M.; Ismail, M.; Jacquet, M.; Janauschek, L.; Janssen, X.; Jemanov, V.; Jonsson, L.; Johnson, D.P.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, Christian M.; Klein, M.; Kleinwort, C.; Klimkovich, T.; Kluge, T.; Knies, G.; Knutsson, A.; Korbel, V.; Kostka, P.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Landon, M.P.J.; Lange, W.; Lastovicka, T.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Lindfeld, L.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Lobodzinska, E.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lucaci-Timoce, A.-I.; Lueders, H.; Luke, D.; Lux, T.; Lytkin, L.; Makankine, A.; Malden, N.; Malinovski, E.; Mangano, S.; Marage, P.; Marshall, R.; Martisikova, M.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Milstead, D.; Mladenov, D.; Mohamed, A.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Muller, K.; Murin, P.; Nankov, K.; Naroska, B.; Naumann, Th.; Newman, Paul R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Oganezov, R.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Papadopoulou, T.; Pascaud, C.; Patel, G.D.; Peng, H.; Perez, E.; Perez-Astudillo, D.; Perieanu, A.; Petrukhin, A.; Pitzl, D.; Placakyte, R.; Portheault, B.; Povh, B.; Prideaux, P.; Rahmat, A.J.; Raicevic, N.; Reimer, P.; Rimmer, A.; Risler, C.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rurikova, Z.; Rusakov, S.; Salvaire, F.; Sankey, D.P.C.; Sauvan, E.; Schatzel, S.; Schmidt, S.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Sloan, T.; Smirnov, P.; Soloviev, Y.; South, D.; Spaskov, V.; Specka, Arnd E.; Steder, M.; Stella, B.; Stiewe, J.; Straumann, U.; Sunar, D.; Tchoulakov, V.; Thompson, Graham; Thompson, P.D.; Toll, T.; Tomasz, F.; Traynor, D.; Truol, P.; Tsakov, I.; Tsipolitis, G.; Tsurin, I.; Turnau, J.; Tzamariudaki, E.; Urban, K.; Urban, Marcel; Usik, A.; Utkin, D.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vazdik, Ya.; Veelken, C.; Vinokurova, S.; Volchinski, V.; Wacker, K.; Weber, G.; Weber, R.; Wegener, D.; Werner, C.; Wessels, M.; Wessling, B.; Wissing, Ch.; Wolf, R.; Wunsch, E.; Xella, S.; Yan, W.; Yeganov, V.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhelezov, A.; Zhokin, A.; Zhu, Y.C.; Zimmermann, J.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

    2006-01-01

    The diffractive photoproduction of rho mesons, e p \\to e rho Y, with large momentum transfer squared at the proton vertex, |t|, is studied with the H1 detector at HERA using an integrated luminosity of 20.1 pb^{-1}. The photon-proton centre of mass energy spans the range 75 < W < 95 GeV, the photon virtuality is restricted to Q^2 < 0.01 GeV^2 and the mass M_Y of the proton remnant is below 5 GeV. The t dependence of the cross section is measured for the range 1.5 < |t| < 10.0 GeV^2 and is well described by a power law, dsigma/ d|t| \\propto |t|^{-n}. The spin density matrix elements, which provide information on the helicity structure of the interaction, are extracted using measurements of angular distributions of the rho decay products. The data indicate a violation of s-channel helicity conservation, with contributions from both single and double helicity-flip being observed. The results are compared to the predictions of perturbative QCD models.

  11. A Study of Spin Alignment of $\\rho(770)^{\\pm}$ and $\\omega(782)$ Mesons in Hadronic $Z^{0}$ Decays

    CERN Document Server

    Abbiendi, G.; Alexander, G.; Allison, John; Altekamp, N.; Anderson, K.J.; Anderson, S.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Batley, J.R.; Baumann, S.; Bechtluft, J.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bellerive, A.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bloodworth, I.J.; Bock, P.; Bohme, J.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couchman, J.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Davis, R.; De Jong, S.; De Roeck, A.; Dervan, P.; Desch, K.; Dienes, B.; Dixit, M.S.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Estabrooks, P.G.; Etzion, E.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Feld, L.; Fiedler, F.; Fierro, M.; Fleck, I.; Frey, A.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gascon, J.; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Gibson, V.; Gibson, W.R.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Graham, K.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Harder, K.; Harel, A.; Hargrove, C.K.; Harin-Dirac, M.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hobson, P.R.; Hocker, James Andrew; Hoffman, Kara Dion; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klier, A.; Kobayashi, T.; Kobel, M.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kyberd, P.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lauber, J.; Lawson, I.; Layter, J.G.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Lu, J.; Ludwig, J.; Lui, D.; Macchiolo, A.; Macpherson, A.; Mader, W.; Mannelli, M.; Marcellini, S.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Merritt, F.S.; Mes, H.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poffenberger, P.; Poli, B.; Polok, J.; Przybycien, M.; Quadt, A.; Rembser, C.; Rick, H.; Robertson, S.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rosati, S.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Sittler, A.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Sproston, M.; Stahl, A.; Stephens, K.; Steuerer, J.; Stoll, K.; Strom, David M.; Strohmer, R.; Surrow, B.; Talbot, S.D.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomas, J.; Thomson, M.A.; Torrence, E.; Towers, S.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Voss, H.; Wackerle, F.; Wagner, A.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wermes, N.; Wetterling, D.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Zacek, V.; Zer-Zion, D.

    2000-01-01

    The helicity density matrix elements rho[00] of rho(770)+- and omega(782) mesons produced in Z decays have been measured using the OPAL detector at LEP. Over the measured meson energy range, the values are compatible with 1/3, corresponding to a statistical mix of helicity -1, 0 and +1 states. For the highest accessible scaled energy range 0.3 < x_E < 0.6, the measured rho[00] values of the rho(770)+- and the omega are 0.373 +- 0.052 and 0.142 +- 0.114, respectively. These results are compared to measurements of other vector mesons.

  12. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

    International Nuclear Information System (INIS)

    Hwang, Melissa; Peddibhotla, Sirisha; McHenry, Peter; Chang, Peggy; Yochum, Zachary; Park, Ko Un; Sears, James Cooper; Vargo-Gogola, Tracy

    2012-01-01

    Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis

  13. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Melissa [Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617 (United States); Peddibhotla, Sirisha [Department of Molecular and Human Genetics, Baylor College of Medicine, John P. McGovern Campus, NABS-0250, Houston, TX 77030 (United States); McHenry, Peter [Department of Biology, Southwestern Adventist University, 100 W. Hillcrest, Keene, TX 76059 (United States); Chang, Peggy; Yochum, Zachary; Park, Ko Un; Sears, James Cooper; Vargo-Gogola, Tracy, E-mail: vargo-gogola.1@nd.edu [Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617 (United States)

    2012-04-25

    Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis.

  14. Comparisons of actin filament disruptors and Rho kinase inhibitors as potential antiglaucoma medications

    OpenAIRE

    Tian, Baohe; Kaufman, Paul L

    2012-01-01

    Dynamics of the actin cytoskeleton in the trabecular meshwork play a crucial role in the regulation of trabecular outflow resistance. The actin filament disruptors and Rho kinase inhibitors affect the dynamics of the actomyosin system by either disrupting the actin filaments or inhibiting the Rho kinase-activated cellular contractility. Both approaches induce similar morphological changes and resistance decreases in the trabecular outflow pathway, and thus both have potential as antiglaucoma ...

  15. QCD and resonance physics. The rho-ω mixing

    International Nuclear Information System (INIS)

    Shifman, M.A.; Vainshtein, A.I.; Zakharov, V.I.

    1978-01-01

    The QCD-based approach to the resonance physics proposed earlier is extended to cover the rho-ω mixing problem. A two-point function relevant to the problem with account of nonperturbative contributions is considered. The sum rules are derived and related phenomenology is introduced. The rho-ω interference is found to be due to the relatively strong isotopic symmetry breaking in the quark masses, and a solution with msub(u) = 0, msub(d) not equal to 0 seems to be ruled out. It is shown that virtual photon exchanges alone can not explain the observed value of the mixing parameter. The phenomenon gets a natural explanation if one assumes a large isotopic symmetry violation in the mechanical quark masses, (msub(d) - msub(u))/(msub(d) + msub(u)) approximately 0.3. This number is close to that resulting from the well-known pseudoscalar meson analysis. Unlike the latter, the result, however, does not assume an exact SU(3)sub(flavor) symmetry in vacuum-to-vacuum matrix elements

  16. Increased RhoA prenylation in the loechrig (loe mutant leads to progressive neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Mandy Cook

    Full Text Available The Drosophila mutant loechrig (loe shows age-dependent degeneration of the nervous system and is caused by the loss of a neuronal isoform of the AMP-activated protein kinase (AMPK γ-subunit (also known as SNF4Aγ. The trimeric AMPK complex is activated by low energy levels and metabolic insults and regulates multiple important signal pathways that control cell metabolism. A well-known downstream target of AMPK is hydroxyl-methylglutaryl-CoA reductase (HMGR, a key enzyme in isoprenoid synthesis, and we have previously shown that HMGR genetically interacts with loe and affects the severity of the degenerative phenotype. Prenylation of proteins like small G-proteins is an important posttranslational modification providing lipid moieties that allow the association of these proteins with membranes, thereby facilitating their subsequent activation. Rho proteins have been extensively studied in neuronal outgrowth, however, much less is known about their function in neuronal maintenance. Here we show that the loe mutation interferes with isoprenoid synthesis, leading to increased prenylation of the small GTPase Rho1, the fly orthologue of vertebrate RhoA. We also demonstrate that increased prenylation and Rho1 activity causes neurodegeneration and aggravates the behavioral and degenerative phenotypes of loe. Because we cannot detect defects in the development of the central nervous system in loe, this suggests that loe only interferes with the function of the RhoA pathway in maintaining neuronal integrity during adulthood. In addition, our results show that alterations in isoprenoids can result in progressive neurodegeneration, supporting findings in vertebrates that prenylation may play a role in neurodegenerative diseases like Alzheimer's Disease.

  17. Measurement of the CKM Angle Alpha at the BABAR Detector Using B Meson Decays to Rho Final States

    Energy Technology Data Exchange (ETDEWEB)

    Mihalyi, Attila; /Wisconsin U., Madison

    2006-10-16

    This thesis contains the results of an analysis of B{sup 0} {yields} {rho}{sup +}{rho}{sup -} using 232 million {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. From a fitted signal yield of 617 {+-} 52 events, the longitudinal polarizations fraction, f{sub L}, of the decay is measured to be 0.978 {+-} 0.014(stat){sub -0.029}{sup +0.021}(syst). The nearly fully longitudinal dominance of the B{sup 0} {yields} {rho}{sup +}{rho}{sup -} decay allows for a measurement of the time dependent CP parameters S{sub L} and C{sub L}, where the first parameter is sensitive to mixing induced CP violation and the second one to direct CP violation. From the same signal yield, these values are found to be S{sub L} = -0.33 {+-} 0.24(stat){sub -0.14}{sup +0.08}(syst) and C{sub L} = - 0.03 {+-} 0.18(stat) {+-} 0.09(syst). The CKM angle {alpha} is then determined, using these results and the branching fractions and polarizations of the decays B{sup 0} {yields} {rho}{sup 0}{rho}{sup 0} and B{sup +} {yields} {rho}{sup +}{rho}{sup 0}. This measurement is done with an isospin analysis, in which a triangle is constructed from the isospin amplitudes of these three decay modes. A {chi}{sup 2} expression that includes the measured quantities expressed as the lengths of the sides of the isospin triangles is constructed and minimized to determine a confidence level on {alpha}. Selecting the solution compatible with the Standard Model, one obtains {alpha} = 100{sup o} {+-} 13{sup o}.

  18. Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis.

    Science.gov (United States)

    Wang, S; Duan, H; Zhang, Y; Sun, F Q

    2016-03-01

    Adenomyosis (ADS) is a common estrogen-dependent gynecological disease with unknown etiology. The RhoA/Rho-kinase (ROCK) signaling pathway is involved in various cellular functions, including migration, proliferation, and smooth muscle contraction. Here we examined the potential role of this pathway in junctional zone (JZ) contraction in women with and without ADS. We demonstrated that in the normal JZ, RhoA and ROCK-I messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. Expression of RhoA and ROCK-I in the JZ from women with ADS was significantly higher than in the control women and showed no significant differences across the menstrual cycle. Treatment of JZ smooth muscle cells (JZSMCs) with estrogen at 0, 1, 10, or 100 nmol/L for 24 hours resulted in increased expression of RhoA, ROCK-I, and myosin light-chain (MLC) phosphorylation (p-MLC) in a dose-dependent manner. In parallel to its effects on p-MLC, estrogen-mediated, dose-dependent contraction responses in JZSMCs. Estrogen-mediated contraction in the ADS group was significantly higher than in the controls and also showed no significant differences across the menstrual cycle. These effects were suppressed in the presence of ICI 182780 or Y27632, supporting an estrogen receptor-dependent and RhoA activation-dependent mechanism. Our results indicate that the level of RhoA and ROCK-I increases in patients with ADS and the cyclic change is lost. Estrogen may affect uterine JZ contraction of ADS by enhancing RhoA/ ROCK-I signaling. © The Author(s) 2015.

  19. The rho-exchange isovector parity-violating potential

    International Nuclear Information System (INIS)

    McKellar, B.H.J.

    1979-01-01

    It is shown that the rho-exchange isovector parity-violating potential is constrained by PCAC to be much weaker than the π-exchange potential and much weaker than recently proposed by Galic et al (J. Phys. G.; 5: L113 (1979)). This potential does not therefore provide a mechanism for suppressing enhanced neutral-current effects in the π-exchange potential. (author)

  20. Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension.

    Science.gov (United States)

    Su, Hao; Yan, Ji; Xu, Jian; Fan, Xi-Zhen; Sun, Xian-Lin; Chen, Kang-Yu

    2015-08-01

    Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC50 = 0.22 and 0.95 μM, respectively. Structural examination suggested that complicated networks of non-bonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.

  1. Fabrication and non-covalent modification of highly oriented thin films of a zeolite-like metal-organic framework (ZMOF) with rho topology

    KAUST Repository

    Shekhah, Osama

    2015-01-01

    Here we report the fabrication of the first thin film of a zeolite-like metal-organic framework (ZMOF) with rho topology (rho-ZMOF-1, ([In48(HImDC)96]48-)n) in a highly oriented fashion on a gold-functionalized substrate. The oriented rho-ZMOF-1 film was functionalized by non-covalent modification via post-synthetic exchange of different probe molecules, such as acridine yellow, methylene blue, and Nile red. In addition, encapsulation of a porphyrin moiety was achieved via in situ synthesis and construction of the rho-ZMOF. Adsorption kinetics of volatile organic compounds on rho-ZMOF-1 thin films was also investigated. This study suggests that rho-ZMOF-1 thin films can be regarded as a promising platform for various applications such as sensing and catalysis. This journal is

  2. Study on Surface Structure of U1-yGdyO2-x Using Raman Spectroscopy

    International Nuclear Information System (INIS)

    Lee, Jeong Mook; Kim, Jan Dee; Youn, Young Sang; Kim, Jong Goo; Ha, Yeong Keong; Kim, Jong Yun

    2016-01-01

    To understand the structural character of the spent nuclear fuel, rare earth element (REE) doped UO 2±x have been studied as simulated spent fuel. The REE doping effect has influence on the phase stability in U-FP-O system, thermal conductivity and the relevant fuel performance. Raman spectroscopy has been used to investigate surface structure of the nuclear fuel materials, because of its sensitivity, convenience and non-destructive sample preparation. The Raman studies on trivalent-doped UO 2 directly show the defect due to oxygen vacancy that could be created by loss of oxygen for charge compensation. This defect has significant effect on the kinetics of fuel oxidation. In this study, we have been investigated the effect on Gd-doping on the UO 2 structure with Raman spectroscopy to characterize the defect structure of nuclear fuel material. The oxygen deficiencies of pellets were estimated by the relation between the doping concentration and a lattice parameter evaluated from XRD spectra. The Raman spectra of U 1-y GdyO 2-x solid solution pellets show the distorted fluorite structure with defect structure due to oxygen vacancies with increasing Gd contents.

  3. Study on Surface Structure of U1-yGdyO2-x Using Raman Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Mook; Kim, Jan Dee; Youn, Young Sang; Kim, Jong Goo; Ha, Yeong Keong; Kim, Jong Yun [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    To understand the structural character of the spent nuclear fuel, rare earth element (REE) doped UO{sub 2±x} have been studied as simulated spent fuel. The REE doping effect has influence on the phase stability in U-FP-O system, thermal conductivity and the relevant fuel performance. Raman spectroscopy has been used to investigate surface structure of the nuclear fuel materials, because of its sensitivity, convenience and non-destructive sample preparation. The Raman studies on trivalent-doped UO{sub 2} directly show the defect due to oxygen vacancy that could be created by loss of oxygen for charge compensation. This defect has significant effect on the kinetics of fuel oxidation. In this study, we have been investigated the effect on Gd-doping on the UO{sub 2} structure with Raman spectroscopy to characterize the defect structure of nuclear fuel material. The oxygen deficiencies of pellets were estimated by the relation between the doping concentration and a lattice parameter evaluated from XRD spectra. The Raman spectra of U{sub 1-y}GdyO{sub 2-x} solid solution pellets show the distorted fluorite structure with defect structure due to oxygen vacancies with increasing Gd contents.

  4. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Science.gov (United States)

    Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru

    2013-01-01

    The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  5. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshinori Kagawa

    Full Text Available The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP, was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  6. Relative Proper Motions in the Rho Ophiuchi Cluster

    Science.gov (United States)

    2016-01-06

    identified as YSOs and may be newly identified cluster members. Key words: ISM: individual objects (Rho Ophiuchi cloud) – stars: formation – stars: pre-main...sequence 1. INTRODUCTION The majority of stars in the Galaxy form in clusters that once the binding mass of the molecular gas is removed, disperse into

  7. HAWC+/SOFIA observations of Rho Oph A: far-infrared polarization spectrum

    Science.gov (United States)

    Santos, Fabio; Dowell, Charles D.; Houde, Martin; Looney, Leslie; Lopez-Rodriguez, Enrique; Novak, Giles; Ward-Thompson, Derek; HAWC+ Science Team

    2018-01-01

    In this work, we present preliminary results from the HAWC+ far-infrared polarimeter that operates on the SOFIA airborne observatory. The densest portions of the Rho Ophiuchi molecular complex, known as Rho Oph A, have been mapped using HAWC+ bands C (89 microns) and D (155 microns). Rho Oph A is a well known nearby star forming region. At the target's distance of approximately 130 pc, our observations provide excellent spatial resolution (~5 mpc in band C).The magnetic field map suggests a compressed and distorted field morphology around Oph S1, a massive B3 star that is the main heat source of Rho Oph A. We compute the ratio p(D)/p(C), where p(C) and p(D) are the polarization degree maps at bands C and D, respectively. This ratio estimates the slope of the polarization spectrum in the far-infrared. Although the slope is predicted to be positive by dust grain models, previous observations of other molecular clouds have revealed that negative slopes are common. In Rho Oph A, we find that there is a smooth gradient of p(D)/p(C) across the mapped field. The change in p(D)/p(C) is well correlated with the integrated NH3 (1,1) emission. A positive slope dominates the lower density and well illuminated portions of the cloud, whereas a transition to a negative slope is observed at the denser and less evenly illuminated cloud core.We interpret the positive to negative slope transition as being consistent with the radiative torques (RATs) grain alignment theory. For the sight lines of higher column density, polarized emission from the warmer outer cloud layers is added to emission from the colder inner well-shielded layers lying along the same line-of-sight. Given that the outer layers receive more radiation from Oph S1, their grain alignment efficiency is expected to be higher according to RATs. The combination of warmer, well aligned grains with cooler, poorly aligned grains is what causes the negative slope. This effect is not present in the sight lines of lower column

  8. Maturation and integration of adult born hippocampal neurons: signal convergence onto small Rho GTPases

    Directory of Open Access Journals (Sweden)

    Krishna eVadodaria

    2013-08-01

    Full Text Available Adult neurogenesis, restricted to specific regions in the mammalian brain, represents one of the most interesting forms of plasticity in the mature nervous system. Adult-born hippocampal neurons play important roles in certain forms of learning and memory, and altered hippocampal neurogenesis has been associated with a number of neuropsychiatric diseases such as major depression and epilepsy. Newborn neurons go through distinct developmental steps from a dividing neurogenic precursor to a synaptically integrated mature neuron. Previous studies have uncovered several molecular signaling pathways involved in distinct steps of this maturational process. In this context, the small Rho GTPases, Cdc42, Rac1 and RhoA have recently been shown to regulate the morphological and synaptic maturation of adult-born dentate granule cells in vivo. Distinct upstream regulators, including several growth factors that modulate maturation and integration of newborn neurons have been shown to also recruit the small Rho GTPases. Here we review recent findings and highlight the possibility that small Rho GTPases may act as central assimilators, downstream of critical input onto adult-born hippocampal neurons contributing to their maturation and integration into the existing dentate gyrus circuitry.

  9. UNC-73/trio RhoGEF-2 activity modulates Caenorhabditis elegans motility through changes in neurotransmitter signaling upstream of the GSA-1/Galphas pathway.

    Science.gov (United States)

    Hu, Shuang; Pawson, Tony; Steven, Robert M

    2011-09-01

    Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Gαq and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments. We found that UNC-73E acts within peptidergic neurons of mature animals to regulate locomotion rate. Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology and weak resistance to the acetylcholinesterase inhibitor aldicarb, they are significantly hypersensitive to the acetylcholine receptor agonist levamisole, indicating alterations in acetylcholine neurotransmitter signaling. Consistent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropeptide release from motor neuron dense core vesicles (DCVs). The unc-73 locomotory phenotype is similar to those of rab-2 and unc-31, genes with distinct roles in the DCV-mediated secretory pathway. We observed that constitutively active Gαs pathway mutations, which compensate for DCV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes. Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitter signaling and may function in the DCV-mediated neuromodulatory regulation of locomotion rate.

  10. Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations

    Science.gov (United States)

    Verboon, Jeffrey M.; Rahe, Travis K.; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

    2015-01-01

    Drosophila immune cells, the hemocytes, undergo four stereotypical developmental migrations to populate the embryo, where they provide immune reconnoitering, as well as a number of non–immune-related functions necessary for proper embryogenesis. Here, we describe a role for Rho1 in one of these developmental migrations in which posteriorly located hemocytes migrate toward the head. This migration requires the interaction of Rho1 with its downstream effector Wash, a Wiskott–Aldrich syndrome family protein. Both Wash knockdown and a Rho1 transgene harboring a mutation that prevents Wash binding exhibit the same developmental migratory defect as Rho1 knockdown. Wash activates the Arp2/3 complex, whose activity is needed for this migration, whereas members of the WASH regulatory complex (SWIP, Strumpellin, and CCDC53) are not. Our results suggest a WASH complex–independent signaling pathway to regulate the cytoskeleton during a subset of hemocyte developmental migrations. PMID:25739458

  11. p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Singh, Nikhlesh K; Janjanam, Jagadeesh; Rao, Gadiparthi N

    2017-08-25

    Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2-G i/o -Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Double-spin asymmetries in the cross section of rho sup 0 and phi production at intermediate energies

    CERN Document Server

    Airapetian, A; Akopov, Z; Amarian, M

    2003-01-01

    Double-spin asymmetries in the cross section of electroproduction of rho sup 0 and phi mesons on the proton and deuteron are measured at the HERMES experiment. The photoabsorption asymmetry in exclusive rho sup 0 electroproduction on the proton exhibits a positive tendency. This is consistent with theoretical predictions that the exchange of an object with unnatural parity contributes to exclusive rho sup 0 electroproduction by transverse photons. The photoabsorption asymmetry on the deuteron is found to be consistent with zero. Double-spin asymmetries in rho sup 0 and phi meson electroproduction by quasi-real photons were also found to be consistent with zero; the asymmetry in the case of the phi meson is compatible with a theoretical prediction which involves s anti s knockout from the nucleon. (orig.)

  13. Structure directing agents induced morphology evolution and phase transition from indium-based rho- to sod-ZMOF

    KAUST Repository

    Shi, Yanshu; Cairns, Amy; Liu, Yunling; Belmabkhout, Youssef; Cai, Xuechao; Pang, Maolin; Eddaoudi, Mohamed

    2017-01-01

    In this report, indium-based rho-and sod-ZMOFs with different morphologies and sizes were prepared. Simultaneous morphology evolution and phase transformation from porous rho-to nonporous sod-ZMOFs were reported for the first time by simply varying the concentration of structure directing agents (SDAs).

  14. Structure directing agents induced morphology evolution and phase transition from indium-based rho- to sod-ZMOF

    KAUST Repository

    Shi, Yanshu

    2017-06-23

    In this report, indium-based rho-and sod-ZMOFs with different morphologies and sizes were prepared. Simultaneous morphology evolution and phase transformation from porous rho-to nonporous sod-ZMOFs were reported for the first time by simply varying the concentration of structure directing agents (SDAs).

  15. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

    Science.gov (United States)

    Kutys, Matthew L; Yamada, Kenneth M

    2014-09-01

    Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

  16. Measurements of Branching Ratios And Search for CP Violation in the Modes B0 to Rho Pi, Rho K

    Energy Technology Data Exchange (ETDEWEB)

    Laplace, Sandrine; /Paris U., VI-VII

    2006-09-18

    The BABAR experiment, at the PEP-II collider at SLAC, has been studying since 1999 CP violation in the B meson system. After the precise measurement of sin2{beta}, one is now concentrating on measuring the angles {alpha} and {gamma} of the unitarity triangle. The work presented in this thesis concerns the measurement of the angle {alpha} in the B{sup 0} {yields} {rho}{pi} mode.

  17. Methanol conversion to lower olefins over RHO type zeolite

    KAUST Repository

    Masih, Dilshad; Imai, Hiroyuki; Yokoi, Toshiyuki; Kondo, Junkonomura; Tatsumi, Takashi

    2013-01-01

    Eight-membered ring small-pore zeolite of RHO-type topology has been synthesized, characterized and tested for methanol-to-olefin (MTO) reaction. The zeolite was hydrothermally crystallized from the gel with Si/Al ratio of 5.0. It showed a high BET

  18. Regulation of mitotic spindle formation by the RhoA guanine nucleotide exchange factor ARHGEF10

    Directory of Open Access Journals (Sweden)

    Satoh Takaya

    2009-07-01

    Full Text Available Abstract Background The Dbl family guanine nucleotide exchange factor ARHGEF10 was originally identified as the product of the gene associated with slowed nerve-conduction velocities of peripheral nerves. However, the function of ARHGEF10 in mammalian cells is totally unknown at a molecular level. ARHGEF10 contains no distinctive functional domains except for tandem Dbl homology-pleckstrin homology and putative transmembrane domains. Results Here we show that RhoA is a substrate for ARHGEF10. In both G1/S and M phases, ARHGEF10 was localized in the centrosome in adenocarcinoma HeLa cells. Furthermore, RNA interference-based knockdown of ARHGEF10 resulted in multipolar spindle formation in M phase. Each spindle pole seems to contain a centrosome consisting of two centrioles and the pericentriolar material. Downregulation of RhoA elicited similar phenotypes, and aberrant mitotic spindle formation following ARHGEF10 knockdown was rescued by ectopic expression of constitutively activated RhoA. Multinucleated cells were not increased upon ARHGEF10 knockdown in contrast to treatment with Y-27632, a specific pharmacological inhibitor for the RhoA effector kinase ROCK, which induced not only multipolar spindle formation, but also multinucleation. Therefore, unregulated centrosome duplication rather than aberration in cytokinesis may be responsible for ARHGEF10 knockdown-dependent multipolar spindle formation. We further isolated the kinesin-like motor protein KIF3B as a binding partner of ARHGEF10. Knockdown of KIF3B again caused multipolar spindle phenotypes. The supernumerary centrosome phenotype was also observed in S phase-arrested osteosarcoma U2OS cells when the expression of ARHGEF10, RhoA or KIF3B was abrogated by RNA interference. Conclusion Collectively, our results suggest that a novel RhoA-dependent signaling pathway under the control of ARHGEF10 has a pivotal role in the regulation of the cell division cycle. This pathway is not involved in

  19. Role of contractile prostaglandins and Rho-kinase in growth factor-induced airway smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2005-07-01

    Full Text Available Abstract Background In addition to their proliferative and differentiating effects, several growth factors are capable of inducing a sustained airway smooth muscle (ASM contraction. These contractile effects were previously found to be dependent on Rho-kinase and have also been associated with the production of eicosanoids. However, the precise mechanisms underlying growth factor-induced contraction are still unknown. In this study we investigated the role of contractile prostaglandins and Rho-kinase in growth factor-induced ASM contraction. Methods Growth factor-induced contractions of guinea pig open-ring tracheal preparations were studied by isometric tension measurements. The contribution of Rho-kinase, mitogen-activated protein kinase (MAPK and cyclooxygenase (COX to these reponses was established, using the inhibitors Y-27632 (1 μM, U-0126 (3 μM and indomethacin (3 μM, respectively. The Rho-kinase dependency of contractions induced by exogenously applied prostaglandin F2α (PGF2α and prostaglandin E2 (PGE2 was also studied. In addition, the effects of the selective FP-receptor antagonist AL-8810 (10 μM and the selective EP1-antagonist AH-6809 (10 μM on growth factor-induced contractions were investigated, both in intact and epithelium-denuded preparations. Growth factor-induced PGF2α-and PGE2-release in the absence and presence of Y-27632, U-0126 and indomethacin, was assessed by an ELISA-assay. Results Epidermal growth factor (EGF-and platelet-derived growth factor (PDGF-induced contractions of guinea pig tracheal smooth muscle preparations were dependent on Rho-kinase, MAPK and COX. Interestingly, growth factor-induced PGF2α-and PGE2-release from tracheal rings was significantly reduced by U-0126 and indomethacin, but not by Y-27632. Also, PGF2α-and PGE2-induced ASM contractions were largely dependent on Rho-kinase, in contrast to other contractile agonists like histamine. The FP-receptor antagonist AL-8810 (10 μM significantly

  20. T^{\\sigma}_{\\rho}(G) Theories and Their Hilbert Series

    CERN Document Server

    Cremonesi, Stefano; Mekareeya, Noppadol; Zaffaroni, Alberto

    2015-01-01

    We give an explicit formula for the Higgs and Coulomb branch Hilbert series for the class of 3d N=4 superconformal gauge theories T^{\\sigma}_{\\rho}(G) corresponding to a set of D3 branes ending on NS5 and D5-branes, with or without O3 planes. Here G is a classical group, \\sigma is a partition of G and \\rho a partition of the dual group G^\\vee. In deriving such a formula we make use of the recently discovered formula for the Hilbert series of the quantum Coulomb branch of N=4 superconformal theories. The result can be expressed in terms of a generalization of a class of symmetric functions, the Hall-Littlewood polynomials, and can be interpreted in mathematical language in terms of localization. We mainly consider the case G=SU(N) but some interesting results are also given for orthogonal and symplectic groups.

  1. Involvement of Rho kinase in the pathogenesis of acute pulmonary embolism-induced polystyrene microspheres in rats.

    Science.gov (United States)

    Toba, M; Nagaoka, T; Morio, Y; Sato, K; Uchida, K; Homma, N; Takahashi, K

    2010-03-01

    Acute pulmonary embolism (PE) is a life-threatening disease, and several vasoconstrictors, including endothelin-1 (ET-1), play a key role in vasoconstriction and hypoxemia during the development of PE. Rho kinase is activated by various vasoconstrictors resulting in vascular contraction and remodeling. Recent evidence has revealed an important role of Rho kinase in the pathogenesis of systemic and pulmonary vascular diseases. However, contribution of Rho kinase in PE remains unclear. We thus investigated the role of Rho kinase in the PE rat model induced by intrajugular administration of polystyrene microspheres (mean diameter, 26 microm). At 6 h following the administration of microspheres (1.5 ml/kg), right ventricular systolic pressure (RVSP) was higher in the PE than in the control rats (15.8 +/- 1.6 vs. 32.9 +/- 7.5 mmHg). Arterial oxygen tension was lower (92.3 +/- 12.5 vs. 66.0 +/- 17.7 Torr), and alveolar-arterial difference in oxygen partial pressure was higher (3.9 +/- 3.8 vs. 36.5 +/- 26.9 Torr) in the PE rats. Western blotting analysis revealed upregulation and downregulation in expression of vascular cell adhesion molecule-1 and endothelial nitric oxide synthase in lungs from the PE rats, respectively, and radioimmunoassay demonstrated an increase in plasma ET-1 levels. Lung Rho kinase alpha expression was greater in the PE rats. At 5 h following administration of microspheres (0.75 ml/kg), intravenous Rho kinase inhibitors HA1077 and Y27632 (3 mg/kg each) attenuated elevation of RVSP (22.0 +/- 3.7, 17.1 +/- 3.2, 14.3 +/- 2.6 mmHg, PE, PE+HA1077, PE+Y27632) and the severity of hypoxemia (66.3 +/- 16.2, 94.9 +/- 23.0, 89.1 +/- 8.5 Torr, PE, PE+HA1077, PE+Y27632) in the PE rats. These results suggest that pulmonary endothelial dysfunction and activation of Rho kinase may contribute to the potentiation of vasoconstriction and hypoxemia in the PE rats.

  2. Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

    Science.gov (United States)

    Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

    2015-04-01

    Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Rho0 production and possible modification in Au+Au and p+p collisions at square root [sNN] = 200 GeV.

    Science.gov (United States)

    Adams, J; Adler, C; Aggarwal, M M; Ahammed, Z; Amonett, J; Anderson, B D; Arkhipkin, D; Averichev, G S; Badyal, S K; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Bekele, S; Belaga, V V; Bellwied, R; Berger, J; Bezverkhny, B I; Bhardwaj, S; Bhati, A K; Bichsel, H; Billmeier, A; Bland, L C; Blyth, C O; Bonner, B E; Botje, M; Boucham, A; Brandin, A; Bravar, A; Cadman, R V; Cai, X Z; Caines, H; Calderón de la Barca Sánchez, M; Carroll, J; Castillo, J; Cebra, D; Chaloupka, P; Chattopadhyay, S; Chen, H F; Chen, Y; Chernenko, S P; Cherney, M; Chikanian, A; Christie, W; Coffin, J P; Cormier, T M; Cramer, J G; Crawford, H J; Das, D; Das, S; Derevschikov, A A; Didenko, L; Dietel, T; Dong, W J; Dong, X; Draper, J E; Du, F; Dubey, A K; Dunin, V B; Dunlop, J C; Dutta Majumdar, M R; Eckardt, V; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Estienne, M; Fachini, P; Faine, V; Faivre, J; Fatemi, R; Filimonov, K; Filip, P; Finch, E; Fisyak, Y; Flierl, D; Foley, K J; Fu, J; Gagliardi, C A; Gagunashvili, N; Gans, J; Ganti, M S; Gaudichet, L; Geurts, F; Ghazikhanian, V; Ghosh, P; Gonzalez, J E; Grachov, O; Grebenyuk, O; Gronstal, S; Grosnick, D; Guertin, S M; Gupta, A; Gutierrez, T D; Hallman, T J; Hamed, A; Hardtke, D; Harris, J W; Heinz, M; Henry, T W; Heppelmann, S; Hippolyte, B; Hirsch, A; Hjort, E; Hoffmann, G W; Horsley, M; Huang, H Z; Huang, S L; Hughes, E; Humanic, T J; Igo, G; Ishihara, A; Jacobs, P; Jacobs, W W; Janik, M; Jiang, H; Johnson, I; Jones, P G; Judd, E G; Kabana, S; Kaplan, M; Keane, D; Khodyrev, V Yu; Kiryluk, J; Kisiel, A; Klay, J; Klein, S R; Klyachko, A; Koetke, D D; Kollegger, T; Kopytine, M; Kotchenda, L; Kovalenko, A D; Kramer, M; Kravtsov, P; Kravtsov, V I; Krueger, K; Kuhn, C; Kulikov, A I; Kumar, A; Kunde, G J; Kunz, C L; Kutuev, R Kh; Kuznetsov, A A; Lamont, M A C; Landgraf, J M; Lange, S; Lasiuk, B; Laue, F; Lauret, J; Lebedev, A; Lednický, R; LeVine, M J; Li, C; Li, Q; Lindenbaum, S J; Lisa, M A; Liu, F; Liu, L; Liu, Z; Liu, Q J; Ljubicic, T; Llope, W J; Long, H; Longacre, R S; Lopez-Noriega, M; Love, W A; Ludlam, T; Lynn, D; Ma, J; Ma, Y G; Magestro, D; Mahajan, S; Mangotra, L K; Mahapatra, D P; Majka, R; Manweiler, R; Margetis, S; Markert, C; Martin, L; Marx, J; Matis, H S; Matulenko, Yu A; McClain, C J; McShane, T S; Meissner, F; Melnick, Yu; Meschanin, A; Miller, M L; Milosevich, Z; Minaev, N G; Mironov, C; Mischke, A; Mishra, D; Mitchell, J; Mohanty, B; Molnar, L; Moore, C F; Mora-Corral, M J; Morozov, D A; Morozov, V; De Moura, M M; Munhoz, M G; Nandi, B K; Nayak, S K; Nayak, T K; Nelson, J M; Netrakanti, P K; Nikitin, V A; Nogach, L V; Norman, B; Nurushev, S B; Odyniec, G; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Paic, G; Pal, S K; Panebratsev, Y; Panitkin, S Y; Pavlinov, A I; Pawlak, T; Peitzmann, T; Perevoztchikov, V; Perkins, C; Peryt, W; Petrov, V A; Phatak, S C; Picha, R; Planinic, M; Pluta, J; Porile, N; Porter, J; Poskanzer, A M; Potekhin, M; Potrebenikova, E; Potukuchi, B V K S; Prindle, D; Pruneau, C; Putschke, J; Rai, G; Rakness, G; Raniwala, R; Raniwala, S; Ravel, O; Ray, R L; Razin, S V; Reichhold, D; Reid, J G; Renault, G; Retiere, F; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevski, O V; Romero, J L; Rose, A; Roy, C; Ruan, L J; Sahoo, R; Sakrejda, I; Salur, S; Sandweiss, J; Savin, I; Schambach, J; Scharenberg, R P; Schmitz, N; Schroeder, L S; Schweda, K; Seger, J; Seyboth, P; Shahaliev, E; Shao, M; Shao, W; Sharma, M; Shestermanov, K E; Shimanskii, S S; Singaraju, R N; Simon, F; Skoro, G; Smirnov, N; Snellings, R; Sood, G; Sorensen, P; Sowinski, J; Speltz, J; Spinka, H M; Srivastava, B; Stanislaus, T D S; Stock, R; Stolpovsky, A; Strikhanov, M; Stringfellow, B; Struck, C; Suaide, A A P; Sugarbaker, E; Suire, C; Sumbera, M; Surrow, B; Symons, T J M; Szanto de Toledo, A; Szarwas, P; Tai, A; Takahashi, J; Tang, A H; Thein, D; Thomas, J H; Timoshenko, S; Tokarev, M; Tonjes, M B; Trainor, T A; Trentalange, S; Tribble, R E; Tsai, O; Ullrich, T; Underwood, D G; Van Buren, G; VanderMolen, A M; Varma, R; Vasilevski, I; Vasiliev, A N; Vernet, R; Vigdor, S E; Viyogi, Y P; Voloshin, S A; Vznuzdaev, M; Waggoner, W; Wang, F; Wang, G; Wang, G; Wang, X L; Wang, Y; Wang, Z M; Ward, H; Watson, J W; Webb, J C; Wells, R; Westfall, G D; Whitten, C; Wieman, H; Willson, R; Wissink, S W; Witt, R; Wood, J; Wu, J; Xu, N; Xu, Z; Xu, Z Z; Yamamoto, E; Yepes, P; Yurevich, V I; Yuting, B; Zanevski, Y V; Zhang, H; Zhang, W M; Zhang, Z P; Zhaomin, Z P; Zizong, Z P; Zołnierczuk, P A; Zoulkarneev, R; Zoulkarneeva, J; Zubarev, A N

    2004-03-05

    We report results on rho(770)(0)-->pi(+)pi(-) production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[s(NN)]=200 GeV. This is the first direct measurement of rho(770)(0)-->pi(+)pi(-) in heavy-ion collisions. The measured rho(0) peak in the invariant mass distribution is shifted by approximately 40 MeV/c(2) in minimum bias p+p interactions and approximately 70 MeV/c(2) in peripheral Au+Au collisions. The rho(0) mass shift is dependent on transverse momentum and multiplicity. The modification of the rho(0) meson mass, width, and shape due to phase space and dynamical effects are discussed.

  4. Renoprotective Effects of Atorvastatin in Diabetic Mice: Downregulation of RhoA and Upregulation of Akt/GSK3

    Science.gov (United States)

    Bruder-Nascimento, Thiago; Callera, Glaucia; Montezano, Augusto Cesar; Antunes, Tayze T.; He, Ying; Cat, Aurelie Nguyen Dinh; Ferreira, Nathanne S.; Barreto, Pedro A.; Olivon, Vânia C.; Tostes, Rita C.; Touyz, Rhian M.

    2016-01-01

    Potential benefits of statins in the treatment of chronic kidney disease beyond lipid-lowering effects have been described. However, molecular mechanisms involved in renoprotective actions of statins have not been fully elucidated. We questioned whether statins influence development of diabetic nephropathy through reactive oxygen species, RhoA and Akt/GSK3 pathway, known to be important in renal pathology. Diabetic mice (db/db) and their control counterparts (db/+) were treated with atorvastatin (10 mg/Kg/day, p.o., for 2 weeks). Diabetes-associated renal injury was characterized by albuminuria (albumin:creatinine ratio, db/+: 3.2 ± 0.6 vs. db/db: 12.5 ± 3.1*; *Patorvastatin-treated db/db mice. Increased ROS generation in the renal cortex of db/db mice was also inhibited by atorvastatin. ERK1/2 phosphorylation was increased in the renal cortex of db/db mice. Increased renal expression of Nox4 and proliferating cell nuclear antigen, observed in db/db mice, were abrogated by statin treatment. Atorvastatin also upregulated Akt/GSK3β phosphorylation in the renal cortex of db/db mice. Our findings suggest that atorvastatin attenuates diabetes-associated renal injury by reducing ROS generation, RhoA activity and normalizing Akt/GSK3β signaling pathways. The present study provides some new insights into molecular mechanisms whereby statins may protect against renal injury in diabetes. PMID:27649495

  5. Rho meson decay width in SU(2) gauge theories with 2 fundamental flavours

    CERN Document Server

    Janowski, Tadeusz; Pica, Claudio

    2016-01-01

    SU(2) gauge theories with two quark flavours in the fundamental representation are among the most promising theories of composite dynamics describing the electroweak sector. Three out of five Goldstone bosons in these models become the longitudinal components of the W and Z bosons giving them mass. Like in QCD, we expect a spectrum of excitations which appear as resonances in vector boson scattering, in particular the vector resonance corresponding to the rho-meson in QCD. In this talk I will present the preliminary results of the first calculation of the rho-meson decay width in this theory, which is analogous to rho to two pions decay calculation in QCD. The results presented were calculated in a moving frame with total momentum (0,0,1) on two ensembles. Future plans include using 3 moving frames on a larger set of ensembles to extract the resonance parameters more reliably and also take the chiral and continuum limits.

  6. UNC-73/Trio RhoGEF-2 Activity Modulates Caenorhabditis elegans Motility Through Changes in Neurotransmitter Signaling Upstream of the GSA-1/Gαs Pathway

    Science.gov (United States)

    Hu, Shuang; Pawson, Tony; Steven, Robert M.

    2011-01-01

    Rho-family GTPases play regulatory roles in many fundamental cellular processes. Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migration, muscle arm extension, phagocytosis, and neurotransmission by activating either Rac or Rho GTPase subfamilies. Multiple differentially expressed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains. The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit Gαq and is required for normal rates of locomotion; however, mechanisms of UNC-73 and Rho pathway regulation of locomotion are not clear. To better define UNC-73 function in the regulation of motility we used cell-specific and inducible promoters to examine the temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments. We found that UNC-73E acts within peptidergic neurons of mature animals to regulate locomotion rate. Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology and weak resistance to the acetylcholinesterase inhibitor aldicarb, they are significantly hypersensitive to the acetylcholine receptor agonist levamisole, indicating alterations in acetylcholine neurotransmitter signaling. Consistent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropeptide release from motor neuron dense core vesicles (DCVs). The unc-73 locomotory phenotype is similar to those of rab-2 and unc-31, genes with distinct roles in the DCV-mediated secretory pathway. We observed that constitutively active Gαs pathway mutations, which compensate for DCV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes. Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitter signaling and may function in the DCV-mediated neuromodulatory regulation of locomotion rate. PMID:21750262

  7. Crucial role of rho-kinase in pressure overload-induced right ventricular hypertrophy and dysfunction in mice.

    Science.gov (United States)

    Ikeda, Shohei; Satoh, Kimio; Kikuchi, Nobuhiro; Miyata, Satoshi; Suzuki, Kota; Omura, Junichi; Shimizu, Toru; Kobayashi, Kenta; Kobayashi, Kazuto; Fukumoto, Yoshihiro; Sakata, Yasuhiko; Shimokawa, Hiroaki

    2014-06-01

    Right ventricular (RV) failure is the leading cause of death in various cardiopulmonary diseases, including pulmonary hypertension. It is generally considered that the RV is vulnerable to pressure overload as compared with the left ventricle (LV). However, as compared with LV failure, the molecular mechanisms of RV failure are poorly understood, and hence therapeutic targets of the disorder remain to be elucidated. Thus, we aimed to identify molecular therapeutic targets for RV failure in a mouse model of pressure overload. To induce pressure overload to respective ventricles, we performed pulmonary artery constriction or transverse aortic constriction in mice. We first performed microarray analysis and found that the molecules related to RhoA/Rho-kinase and integrin pathways were significantly upregulated in the RV with pulmonary artery constriction compared with the LV with transverse aortic constriction. Then, we examined the responses of both ventricles to chronic pressure overload in vivo. We demonstrated that compared with transverse aortic constriction, pulmonary artery constriction caused greater extents of mortality, Rho-kinase expression (especially ROCK2 isoform), and oxidative stress in pressure-overloaded RV, reflecting the weakness of the RV in response to pressure overload. Furthermore, mice with myocardial-specific overexpression of dominant-negative Rho-kinase showed resistance to pressure overload-induced hypertrophy and dysfunction associated with reduced oxidative stress. Finally, dominant-negative Rho-kinase mice showed a significantly improved long-term survival in both pulmonary artery constriction and transverse aortic constriction as compared with littermate controls. These results indicate that the Rho-kinase pathway plays a crucial role in RV hypertrophy and dysfunction, suggesting that the pathway is a novel therapeutic target of RV failure in humans. © 2014 American Heart Association, Inc.

  8. Fabrication and non-covalent modification of highly oriented thin films of a zeolite-like metal-organic framework (ZMOF) with rho topology

    KAUST Repository

    Shekhah, Osama; Cadiau, Amandine; Eddaoudi, Mohamed

    2015-01-01

    Here we report the fabrication of the first thin film of a zeolite-like metal-organic framework (ZMOF) with rho topology (rho-ZMOF-1, ([In48(HImDC)96]48-)n) in a highly oriented fashion on a gold-functionalized substrate. The oriented rho-ZMOF-1

  9. Serine34 phosphorylation of RHO guanine dissociation inhibitor (RHOGDI{alpha}) links signaling from conventional protein kinase C to RHO GTPase in cell adhesion

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Choi, Youngsil; Yoneda, Atsuko

    2010-01-01

    . Phosphospecific antibodies reveal endogenous phosphorylation in several cell types that is sensitive to adhesion events triggered, for example, by hepatocyte growth factor. Phosphorylation is also sensitive to PKC inhibition. Together with FRET microscopy sensing GTP-RhoA levels, the data reveal a common pathway...

  10. Effect of QSKL on MAPK and RhoA Pathways in a Rat Model of Heart Failure

    Directory of Open Access Journals (Sweden)

    Kai Xia

    2017-01-01

    Full Text Available Qishenkeli (QSKL is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA and mitogen activated protein kinase (MAPK pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery. Cardiac functions were measured by echocardiography and collagen deposition was assessed by Masson staining. Expressions of the key molecules involved in the RhoA and MAPK pathways were also measured. Twenty-one days after surgery, cardiac functions were severely impaired and collagen deposition was remarkable, while QSKL treatment could improve heart functions and alleviate collagen deposition. Further results demonstrated that the effects may be mediated by suppressing expressions of extracellular signal-regulated kinase (ERK and c-Jun N-terminal kinase (JNK. Moreover, expressions of RhoA, Rho-associated protein kinase 1/2 (ROCK1/2, and phosphorylated myosin light chain (p-MLC were also downregulated by QSKL compared with the model group. The cardioprotective mechanism of QSKL on heart failure is probably mediated by regulating both the MAPK and RhoA signaling pathways.

  11. Raf-1/CK2 and RhoA/ROCK signaling promote TNF-α-mediated endothelial apoptosis via regulating vimentin cytoskeleton.

    Science.gov (United States)

    Yang, Lifeng; Tang, Lian; Dai, Fan; Meng, Guoliang; Yin, Runting; Xu, Xiaole; Yao, Wenjuan

    2017-08-15

    Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α. Both RhoA deficiency and ROCK activity inhibition (Y-27632) greatly inhibited endothelial apoptosis and preserved cell viability in TNF-α-induced human umbilical vein endothelial cells (HUVECs). Also vimentin phosphorylation and the remodeling of vimentin or phospho-vimentin induced by TNF-α were obviously attenuated by RhoA suppression and ROCK inhibition. TNF-α-mediated vimentin cleavage was significantly inhibited by RhoA suppression and ROCK inhibition through decreasing the activation of caspase3 and 8. Furthermore, TNF-α treatment greatly enhanced the activation of Raf-1. Suppression of Raf-1 or CK2 by its inhibitor (GW5074 or TBB) blocked vimentin phosphorylation, remodeling and endothelial apoptosis, and preserved cell viability in TNF-α-induced HUVECs. However, Raf-1 inhibition showed no significant effect on TNF-α-induced ROCK expression and activation, suggesting that the regulation of Raf-1/CK2 signaling on vimentin was independent of ROCK. Taken together, these results indicate that both RhoA/ROCK and Raf-1/CK2 pathway are responsible for TNF-α-mediated endothelial cytotoxicity via regulating vimentin cytoskeleton. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Inverse relationship between TCTP/RhoA and p53/ /cyclin A/actin expression in ovarian cancer cells Inverse relationship between TCTP/RhoA and p53/ /cyclin A/actin expression in ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Malgorzata Kloc

    2012-10-01

    Full Text Available The translationally controlled tumor protein (TCTP plays a role in cell growth, cell cycle and cancer
    progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the
    cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased
    migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,
    a key regulator of cell cycle, controls actin organization and negatively regulates cell motility via regulation of RhoA
    expression. We studied the organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,
    cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 (expressing
    low level of inducible p53 ovarian epithelial cancer cells with different metastatic potential. Immunostaining
    and ultrastructural analyses illustrated a dramatic difference in the organization of the cytokeratin and actin
    filaments in non-transformed versus cancer cell lines. We also determined that there is an inverse relationship between
    the level of TCTP/RhoA and actin/p53/cyclin A expression in ovarian cancer cell lines. This previously unidentified
    negative relationship between TCTP/RhoA and actin/p53/cyclin A may suggest that this interaction is linked
    with the high aggressiveness of ovarian cancers.The translationally controlled tumor protein (TCTP plays a role in cell growth, cell cycle and cancer
    progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the
    cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased
    migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,
    a key regulator of cell cycle, controls actin organization

  13. Rho proteins − the key regulators of cytoskeleton in the progression of mitosis and cytokinesis

    Directory of Open Access Journals (Sweden)

    Anna Klimaszewska

    2011-11-01

    Full Text Available The Rho proteins are members of the Ras superfamily of small GTPases. They are thought to be crucial regulators of multiple signal transduction pathways that influence a wide range of cellular functions, including migration, membrane trafficking, adhesion, polarity and cell shape changes. Thanks to their ability to control the assembly and organization of the actin and microtubule cytoskeletons, Rho GTPases are known to regulate mitosis and cytokinesis progression. These proteins are required for formation and rigidity of the cortex during mitotic cell rounding, mitotic spindle formation and attachment of the spindle microtubules to the kinetochore. In addition, during cytokinesis, they are involved in promoting division plane determination, contractile ring and cleavage furrow formation and abscission. They are also known as regulators of cell cycle progression at the G1/S and G2/M transition. Thus, the signal transduction pathways in which Rho proteins participate, appear to connect dynamics of actin and microtubule cytoskeletons to cell cycle progression. We review the current state of knowledge concerning the molecular mechanisms by which Rho GTPase signaling regulates remodeling of actin and microtubule cytoskeletons in order to control cell division progression.

  14. Exclusive {rho}{sup 0} meson cross section ratios on deuterium and hydrogen targets

    Energy Technology Data Exchange (ETDEWEB)

    Osborne, A.G.S.

    2006-08-15

    The HERMES experiment is a large forward angle spectrometer located at the HERA accelerator ring at DESY, Hamburg. This thesis presents the analysis of the kinematic dependencies of {rho}{sup 0} vector meson production on hydrogen and deuterium targets. The relative gluon and quark contribution to the {rho}{sup 0} production amplitude is expected to depend on the kinematical variable x{sub Bj}, and by measuring the ratio of {rho}{sup 0} electroproduction cross sections on deuterium and hydrogen from HERMES data this dependence is confirmed. This thesis describes the methods used to extract the cross section ratio from the HERMES data taken between the years 1996 and 2000 and compares the results with the theoretical predictions. Until 2005 the missing mass resolution of the HERMES spectrometer was only sufficient to allow exclusivity at the level of a data sample. The HERMES Recoil Detector, installed in early 2006, is an upgrade which will augment the HERMES spectrometer by establishing exclusivity at the event level and therefore improving the resolution to which various kinematical variables may be reconstructed. Additionally, the Recoil Detector will contribute to the overall background suppression capability of the HERMES spectrometer. These improvements will provide a strong reduction in the statistical uncertainties present in the {rho}{sup 0}-analysis and other analyses at HERMES. The Recoil Detector critically relies on its track reconstruction software to enable its capability to provide event level exclusive measurements. This tracking code is presented in detail. (orig.)

  15. Reduction of Fibrogenesis by Selective Delivery of a Rho Kinase Inhibitor to Hepatic Stellate Cells in Mice

    NARCIS (Netherlands)

    van Beuge, M. M.; Prakash, J.; Lacombe, M.; Gosens, R.; Post, E.; Reker-Smit, C.; Beljaars, L.; Poelstra, K.

    One of the pathways activated during liver fibrosis is the Rho kinase pathway, which regulates activation, migration, and contraction of hepatic stellate cells (HSC). Inhibition of this kinase by the Rho kinase inhibitor Y27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide

  16. Coherent rho+ production in neutrino-neon interactions

    International Nuclear Information System (INIS)

    Ballagh, H.C.; Bingham, H.H.; Lawry, T.J.

    1988-01-01

    Coherent rho + production on neon nuclei has been observed in charged-current events in a neutrino bubble-chamber experiment. The incident neutrino energy was 10--320 GeV, with a median event energy of 80 GeV. The rate per charged-current event was (0.28 +- 0.10)%. Comparison was made to vector-meson-dominance predictions; agreement with the overall rate, but disagreement at high neutrino energies and at high Q 2 , was found

  17. Structural determinants for antagonist pharmacology that distinguish the rho1 GABAC receptor from GABAA receptors.

    Science.gov (United States)

    Zhang, Jianliang; Xue, Fenqin; Chang, Yongchang

    2008-10-01

    GABA receptor (GABAR) types C (GABACR) and A (GABAAR) are both GABA-gated chloride channels that are distinguished by their distinct competitive antagonist properties. The structural mechanism underlying these distinct properties is not well understood. In this study, using previously identified binding residues as a guide, we made individual or combined mutations of nine binding residues in the rho1 GABACR subunit to their counterparts in the alpha1beta2gamma2 GABAAR or reverse mutations in alpha1 or beta2 subunits. The mutants were expressed in Xenopus laevis oocytes and tested for sensitivities of GABA-induced currents to the GABAA and GABAC receptor antagonists. The results revealed that bicuculline insensitivity of the rho1 GABACR was mainly determined by Tyr106, Phe138 and Phe240 residues. Gabazine insensitivity of the rho1 GABACR was highly dependent on Tyr102, Tyr106, and Phe138. The sensitivity of the rho1 GABACR to 3-aminopropyl-phosphonic acid and its analog 3-aminopropyl-(methyl)phosphinic acid mainly depended on residues Tyr102, Val140, FYS240-242, and Phe138. Thus, the residues Tyr102, Tyr106, Phe138, and Phe240 in the rho1 GABACR are major determinants for its antagonist properties distinct from those in the GABAAR. In addition, Val140 in the GABACR contributes to 3-APA binding. In conclusion, we have identified the key structural elements underlying distinct antagonist properties for the GABACR. The mechanistic insights were further extended and discussed in the context of antagonists docking to the homology models of GABAA or GABAC receptors.

  18. Inhibition of Rho-associated kinases disturbs the collective cell migration of stratified TE-10 cells

    Directory of Open Access Journals (Sweden)

    Taro Mikami

    2015-01-01

    Full Text Available BACKGROUND: The collective cell migration of stratified epithelial cells is considered to be an important phenomenon in wound healing, development, and cancer invasion; however, little is known about the mechanisms involved. Furthermore, whereas Rho family proteins, including RhoA, play important roles in cell migration, the exact role of Rho-associated coiled coil-containing protein kinases (ROCKs in cell migration is controversial and might be cell-type dependent. Here, we report the development of a novel modified scratch assay that was used to observe the collective cell migration of stratified TE-10 cells derived from a human esophageal cancer specimen. RESULTS: Desmosomes were found between the TE-10 cells and microvilli of the surface of the cell sheet. The leading edge of cells in the cell sheet formed a simple layer and moved forward regularly; these rows were followed by the stratified epithelium. ROCK inhibitors and ROCK small interfering RNAs (siRNAs disturbed not only the collective migration of the leading edge of this cell sheet, but also the stratified layer in the rear. In contrast, RhoA siRNA treatment resulted in more rapid migration of the leading rows and disturbed movement of the stratified portion. CONCLUSIONS: The data presented in this study suggest that ROCKs play an important role in mediating the collective migration of TE-10 cell sheets. In addition, differences between the effects of siRNAs targeting either RhoA or ROCKs suggested that distinct mechanisms regulate the collective cell migration in the simple epithelium of the wound edge versus the stratified layer of the epithelium.

  19. Rho Ophiuchi Cloud Core Extinction Map

    Science.gov (United States)

    Gibson, D. J.; Rudolph, A.; Barsony, M.

    1997-12-01

    We present an extinction map of a one square degree region ( ~ 2.2pc square) of the core of the star-forming region rho Ophiuchi derived by the method of star counts. Photometry from the near-infrared J, H, and K band images of Barsony et al. (1997) provided the stellar catalog for this study. From this map an estimate of the mass of the region is made and compared with previous estimates from other methods. Reference Barsony, M., Kenyon, S.J., Lada, E.A., & Teuben, P.J. 1997, ApJS, 112, 109

  20. Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer.

    Science.gov (United States)

    Assao, Agnes; Nonogaki, Suely; Lauris, José Roberto Pereira; Carvalho, André Lopes; Pinto, Clóvis Antônio Lopes; Soares, Fernando Augusto; Kowalski, Luiz Paulo; Oliveira, Denise Tostes

    2017-06-01

    Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas. The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient's prognosis. The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer's exact test and Spearman's test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test. A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip. Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion. Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.

  1. The Rho kinases I and II regulate different aspects of myosin II activity

    DEFF Research Database (Denmark)

    Yoneda, Atsuko; Multhaupt, Hinke A B; Couchman, John R

    2005-01-01

    The homologous mammalian rho kinases (ROCK I and II) are assumed to be functionally redundant, based largely on kinase construct overexpression. As downstream effectors of Rho GTPases, their major substrates are myosin light chain and myosin phosphatase. Both kinases are implicated in microfilament...... bundle assembly and smooth muscle contractility. Here, analysis of fibroblast adhesion to fibronectin revealed that although ROCK II was more abundant, its activity was always lower than ROCK I. Specific reduction of ROCK I by siRNA resulted in loss of stress fibers and focal adhesions, despite...

  2. Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

    Science.gov (United States)

    Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

    2016-10-01

    Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form

  3. A bacterial cytotoxin identifies the RhoA exchange factor Net1 as a key effector in the response to DNA damage.

    Directory of Open Access Journals (Sweden)

    Lina Guerra

    Full Text Available BACKGROUND: Exposure of adherent cells to DNA damaging agents, such as the bacterial cytolethal distending toxin (CDT or ionizing radiations (IR, activates the small GTPase RhoA, which promotes the formation of actin stress fibers and delays cell death. The signalling intermediates that regulate RhoA activation and promote cell survival are unknown. PRINCIPAL FINDINGS: We demonstrate that the nuclear RhoA-specific Guanine nucleotide Exchange Factor (GEF Net1 becomes dephosphorylated at a critical inhibitory site in cells exposed to CDT or IR. Expression of a dominant negative Net1 or Net1 knock down by iRNA prevented RhoA activation, inhibited the formation of stress fibers, and enhanced cell death, indicating that Net1 activation is required for this RhoA-mediated responses to genotoxic stress. The Net1 and RhoA-dependent signals involved activation of the Mitogen-Activated Protein Kinase p38 and its downstream target MAPK-activated protein kinase 2. SIGNIFICANCE: Our data highlight the importance of Net1 in controlling RhoA and p38 MAPK mediated cell survival in cells exposed to DNA damaging agents and illustrate a molecular pathway whereby chronic exposure to a bacterial toxin may promote genomic instability.

  4. The ionizing radiation inducible gene PARX/ARAP2 participates in Rho and ARF signaling

    International Nuclear Information System (INIS)

    Wong, J.A.; Chen, Z.; Zhao, Y.; Vallis, K.A.; Marignani, P.A.; Randazzo, P.A.

    2003-01-01

    Full text: PARX/ARAP2 is a novel protein that we identified in a gene trap screen for ionizing radiation (IR)-regulated genes. It belongs to a recently described family of proteins that link Rho, ADP-ribosilation factor (ARF) and phosphoinositide 3-kinase (PI3-K) signaling. We have cloned the full length human PARX. Domain analysis of the predicted protein revealed a sterile-alpha motif, five pleckstrin homology domains, a RhoGTPase activating domain (RhoGAP) and an ARF activating domain (ARFGAP). PARX is early inducible by IR in a dose-dependent manner in murine ES cells and in several human B-cell lymphoma lines with up to six-fold induction at the mRNA level at 2 hours (10 Gy). Thus, the kinetics of PARX induction follows the pattern of the rapid response typical of many stress-induced immediate-early genes. PARX expression is also induced in response to other cellular stressors including sorbitol and bleomycin. PARX induction is dependent on PI3-K activity and can be suppressed by the PI3-K inhibitor LY294002. Induction of PARX in response to IR has been observed in cell lines that are p53 mutant indicating up-regulation independent of normal p53 function. The role of p53 in PARX induction is currently being studied using cell lines expressing temperature sensitive p53. Biochemical studies reveal that human PARX has in vivo RhoGAP activity for Rac1 and phosphatidylinositol 3,4,5-trisphosphate dependent ARFGAP activity for ARF1, ARF5 and ARF6. Also, temporal changes in PARX cellular localization following IR are currently being investigated using confocal microscopy. PARX is a gene with a potential role in the cellular response to genotoxic stress, and may illuminate the currently unclear role the small GTPases Rho and ARF play in the radiation response

  5. Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

    Science.gov (United States)

    Goedhart, Joachim; van Unen, Jakobus; Adjobo-Hermans, Merel J W; Gadella, Theodorus W J

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Gαq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined to the cytoplasm. Live-cell imaging studies yielded quantitative information on diffusion coefficients, association rates and encounter times of GEFT and p63RhoGEF. Calcium signaling was examined as a measure of the signal transmission, revealing more efficient signaling through the membrane-associated p63RhoGEF. A rapamycin dependent recruitment system was used to dynamically alter the subcellular location and concentration of GEFT, showing efficient signaling through GEFT only upon membrane recruitment. Together, our results show efficient signal transmission through membrane located effectors, and highlight a role for increased concentration rather than increased encounter times due to membrane localization in the Gαq mediated pathways to p63RhoGEF and PLCβ.

  6. RhoA Activation Sensitizes Cells to Proteotoxic Stimuli by Abrogating the HSF1-Dependent Heat Shock Response.

    Directory of Open Access Journals (Sweden)

    Roelien A M Meijering

    Full Text Available The heat shock response (HSR is an ancient and highly conserved program of stress-induced gene expression, aimed at reestablishing protein homeostasis to preserve cellular fitness. Cells that fail to activate or maintain this protective response are hypersensitive to proteotoxic stress. The HSR is mediated by the heat shock transcription factor 1 (HSF1, which binds to conserved heat shock elements (HSE in the promoter region of heat shock genes, resulting in the expression of heat shock proteins (HSP. Recently, we observed that hyperactivation of RhoA conditions cardiomyocytes for the cardiac arrhythmia atrial fibrillation. Also, the HSR is annihilated in atrial fibrillation, and induction of HSR mitigates sensitization of cells to this disease. Therefore, we hypothesized active RhoA to suppress the HSR resulting in sensitization of cells for proteotoxic stimuli.Stimulation of RhoA activity significantly suppressed the proteotoxic stress-induced HSR in HL-1 atrial cardiomyocytes as determined with a luciferase reporter construct driven by the HSF1 regulated human HSP70 (HSPA1A promoter and HSP protein expression by Western Blot analysis. Inversely, RhoA inhibition boosted the proteotoxic stress-induced HSR. While active RhoA did not preclude HSF1 nuclear accumulation, phosphorylation, acetylation, or sumoylation, it did impair binding of HSF1 to the hsp genes promoter element HSE. Impaired binding results in suppression of HSP expression and sensitized cells to proteotoxic stress.These results reveal that active RhoA negatively regulates the HSR via attenuation of the HSF1-HSE binding and thus may play a role in sensitizing cells to proteotoxic stimuli.

  7. Aging-associated oxidative stress leads to decrease in IAS tone via RhoA/ROCK downregulation.

    Science.gov (United States)

    Singh, Jagmohan; Kumar, Sumit; Krishna, Chadalavada Vijay; Rattan, Satish

    2014-06-01

    Internal anal sphincter (IAS) tone plays an important role in rectoanal incontinence (RI). IAS tone may be compromised during aging, leading to RI in certain patients. We examined the influence of oxidative stress in the aging-associated decrease in IAS tone (AADI). Using adult (4-6 mo old) and aging (24-30 mo old) rats, we determined the effect of oxidative stress on IAS tone and the regulatory RhoA/ROCK signal transduction cascade. We determined the effect of the oxidative stress inducer LY83583, which produces superoxide anions (O2 (·-)), on basal and stimulated IAS tone before and after treatment of intact smooth muscle strips and smooth muscle cells with the O2 (·-) scavenger SOD. Our data showed that AADI was associated with a decrease in RhoA/ROCK expression at the transcriptional and translational levels. Oxidative stress with a LY83583-mediated decrease in IAS tone and relaxation of IAS smooth muscle cells was associated with a decrease in RhoA/ROCK signal transduction, which was reversible by SOD. In addition, LY83583 caused a significant decrease in IAS contraction produced by the RhoA activator and a known RhoA/ROCK agonist, U46619, that was also reversible by SOD. The inhibitory effects of LY83583 and the ROCK inhibitor Y27632 on the U46619-induced increase in IAS tone were similar. We conclude that an increase in oxidative stress plays an important role in AADI in the elderly and may be one of the underlying mechanisms of RI in certain aging patients. Copyright © 2014 the American Physiological Society.

  8. Lipid peroxidation regulates podocyte migration and cytoskeletal structure through redox sensitive RhoA signaling

    Directory of Open Access Journals (Sweden)

    Claudia Kruger

    2018-06-01

    Full Text Available Early podocyte loss is characteristic of chronic kidney diseases (CKD in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes. We found that lipid radicals govern changes in podocyte homeostasis through redox sensitive RhoA signaling: lipid radicals inhibit migration and cause loss of F-actin fibers. These effects were prevented by mutating the redox sensitive cysteines of RhoA. We therefore suggest that in diseases associated with increased lipid peroxidation, lipid radicals can determine podocyte function with potentially pathogenic consequences for kidney physiology. Keywords: Lipid peroxidation, Reactive lipids, Podocyte, RhoA, Cysteine, Chronic kidney disease

  9. RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton.

    Science.gov (United States)

    Tang, Lian; Dai, Fan; Liu, Yan; Yu, Xiaoqiang; Huang, Chao; Wang, Yuqin; Yao, Wenjuan

    2018-05-20

    The RhoA/ROCK signaling pathway regulates cell morphology, adhesion, proliferation, and migration. In this study, we investigated the regulatory role of RhoA/ROCK signaling on PDGF-BB-mediated smooth muscle phenotypic modulation and vascular remodeling and clarified the molecular mechanisms behind these effects. PDGF-BB treatment induced the activation of RhoA, ROCK, PDGF-Rβ, and the expression of PDGF-Rβ in HA-VSMCs (human aortic vascular smooth muscle cells). PDGF-Rβ inhibition and RhoA suppression blocked PDGF-BB-induced RhoA activation and ROCK induction. In addition, PDGF-BB-mediated cell proliferation and migration were suppressed by PDGF-Rβ inhibition, RhoA suppression, and ROCK inhibition, suggesting that PDGF-BB promotes phenotypic modulation of HA-VSMCs by activating the RhoA/ROCK pathway via the PDGF receptor. Moreover, suppressing both ROCK1 and ROCK2 blocked cell cycle progression from G0/G1 to S phase by decreasing the transcription and protein expression of cyclin D1, CDK2, and CDK4 via JNK/c-Jun pathway, thus reducing cell proliferation in PDGF-BB-treated HA-VSMCs. ROCK1 deletion, rather than ROCK2 suppression, significantly inhibited PDGF-BB-induced migration by reducing the expression of vimentin and preventing the remodeling of vimentin and phospho-vimentin. Furthermore, ROCK1 deletion suppressed vimentin by inhibiting the phosphorylation of Smad2/3 and the nuclear translocation of Smad4. These findings suggested that ROCK1 and ROCK2 might play different roles in PDGF-BB-mediated cell proliferation and migration in HA-VSMCs. In addition, PDGF-BB and its receptor participated in neointima formation and vascular remodeling by promoting cell cycle protein expression via the JNK pathway and enhancing vimentin expression in a rat balloon injury model; effects that were inhibited by treatment with fasudil. Together, the results of this study reveal a novel mechanism through which RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and

  10. Color transparency in incoherent electroproduction of {rho} mesons off nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Nemchik, J. [Institute of Experimental Physics SAS, Watsonova 47, 04001 Kosice, Slovakia and Czech Technical University, FNSPE, Brehova 7, 11519 Praque (Czech Republic); Kopeliovich, B. Z.; Potashnikova, I. K. [Departamento de Fisica y Centro de Estudios Subatomicos, Universidad Tecnica Federico Santa Maria, Casilla 110-V, Valparaiso (Chile)

    2013-04-15

    Color transparency (CT) phenomena in elastic electroproduction of vector mesons off nuclei are usually infected by the onset of coherence length (CL) effects. However, at low energies corresponding to the CLAS experiment at Jefferson Lab (JLab), one can study practically the net CT effects, since CL is much shorter than the nuclear radius. We investigate various manifestations of CT effects using rigorous quantum mechanical approach based on the path integral technique. We include also the effects of {rho} meson decay inside the nucleus leading to a rise of the nuclear suppression towards small values of Q{sup 2}. Motivated by the last CLAS data we predict the A, Q{sup 2} and l{sub c} dependence of nuclear transparency for {rho}{sup 0} mesons produced incoherently off nuclei. We also perform predictions for expected signal of CT corresponding to the planned JLab upgrade to 12 GeV electron beam.

  11. 1α,25-Dihydroxyvitamin D3 Ameliorates Seawater Aspiration-Induced Lung Injury By Inhibiting The Translocation Of NF-κB and RhoA.

    Science.gov (United States)

    Zhang, Minlong; Jin, Faguang

    2017-06-01

    Our previous study have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses seawater aspiration-induced ALI in vitro and in vivo. We also have confirmed that treatment with calcitriol ameliorates seawater aspiration-induced inflammation and pulmonary edema via the inhibition of NF-κB and RhoA/Rho kinase pathway activation. In our further work, we investigated the effect of calcitriol on nuclear translocation of NF-κB and membrane translocation of RhoA in vitro. A549 cells and rat pulmonary microvascular endothelial cells (RPMVECs) were cultured with calcitriol or not for 48 h and then stimulated with 25% seawater for 40 min. After these treatments, cells were collected and performed with immunofluorescent staining to observe the translocation of NF-κB and RhoA and the cytoskeleton remodeling. In vitro, seawater stimulation activates nuclear translocation of NF-κB and membrane translocation of RhoA in A549 cells. In addition, seawater administration also induced cytoskeleton remodeling in A549 cells and RPMVECs. However, pretreatment with calcitriol significantly inhibited the activation of NF-κB and RhoA/Rho kinase pathways, as demonstrated by the reduced nuclear translocation of NF-κB and membrane translocation of RhoA in A549 cells. Meanwhile, treatment of calcitriol also regulated the cytoskeleton remodeling in both A549 cells and RPMVECs. These results demonstrated that treatment with calcitriol ameliorates seawater aspiration-induced ALI via inhibition of nuclear translocation of NF-κB and membrane translocation of RhoA and protection of alveolar epithelial and pulmonary microvascular endothelial barrier.

  12. Restoration of uridine 5′-triphosphate-suppressed delayed rectifying K+ currents by an NO activator KMUP-1 involves RhoA/Rho kinase signaling in pulmonary artery smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Zen-Kong Dai

    2016-12-01

    Full Text Available We have demonstrated that KMUP-1 (7-[2-[4-(2-chlorobenzenepiperazinyl]ethyl]-1,3-dimethylxanthine blunts monocrotaline-induced pulmonary arterial hypertension by altering Ca2+ sensitivity, K+-channel function, endothelial nitric oxide synthase activity, and RhoA/Rho kinase (ROCK expression. This study further investigated whether KMUP-1 impedes uridine 5′-triphosphate (UTP-inhibited delayed rectifying K+ (KDR current in rat pulmonary arteries involved the RhoA/ROCK signaling. Pulmonary artery smooth muscle cells (PASMCs were enzymatically dissociated from rat pulmonary arteries. KMUP-1 (30μM attenuated UTP (30μM-mediated membrane depolarization and abolished UTP-enhanced cytosolic Ca2+ concentration. Whole-cell patch-clamp electrophysiology was used to monitor KDR currents. A voltage-dependent KDR current was isolated and shown to consist of a 4-aminopyridine (5mM-sensitive component and an insensitive component. The 4-aminopyridine sensitive KDR current was suppressed by UTP (30μM. The ROCK inhibitor Y27632 (30μM abolished the ability of UTP to inhibit the KDR current. Like Y27632, KMUP-1 (30μM similarly abolished UTP-inhibited KDR currents. Superfused protein kinase A and protein kinase G inhibitors (KT5720, 300nM and KT5823, 300nM did not affect UTP-inhibited KDR currents, but the currents were restored by adding KMUP-1 (30μM to the superfusate. KMUP-1 reversal of KDR current inhibition by UTP predominantly involves the ROCK inhibition. The results indicate that the RhoA/ROCK signaling pathway plays a key role in eliciting PASMCs depolarization caused by UTP, which would result in pulmonary artery constriction. KMUP-1 blocks UTP-mediated PASMCs depolarization, suggesting that it would prevent abnormal pulmonary vasoconstriction.

  13. Tetraspanin CD9 regulates cell contraction and actin arrangement via RhoA in human vascular smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Michael J Herr

    Full Text Available The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided. We utilized a human model of aortic smooth muscle cells to understand the consequences of CD9 deficiency on VSMC phenotypes. Upon knocking down CD9, the cells developed an abnormally small and rounded morphology. We determined that this morphological change was due to a lack of typical parallel actin arrangement. We also found similar total RhoA but decreased GTP-bound (active RhoA levels in CD9 deficient cells. As a result, cells lacking a full complement of CD9 were less contractile than their control treated counterparts. Upon restoration of RhoA activity in the CD9 deficient cells, the phenotype was reversed and cell contraction was restored. Conversely, inhibition of RhoA activity in the control cells mimicked the CD9-deficient cell phenotype. Thus, alteration in CD9 expression was sufficient to profoundly disrupt cellular actin arrangement and endogenous cell contraction by interfering with RhoA signaling. This study provides insight into how CD9 may regulate previously described vascular smooth muscle cell pathophysiology.

  14. Diffractive Electroproduction of rho and phi Mesons at HERA

    CERN Document Server

    Aaron, F.D.; Alexa, C.; Andreev, V.; Antunovic, B.; Asmone, A.; Backovic, S.; Baghdasaryan, A.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Belousov, A.; Bizot, J.C.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J.G.; Coughlan, J.A.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Daum, K.; Deak, M.; de Boer, Y.; Delcourt, B.; Del Degan, M.; Delvax, J.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Falkiewicz, A.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D.J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, S.; Glazov, A.; Glushkov, I.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Helebrant, C.; Henderson, R.C.W.; Hennekemper, E.; Henschel, H.; Herbst, M.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Jacquet, M.; Janssen, M.E.; Janssen, X.; Jonsson, L.; Jung, A.W.; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kluge, T.; Knutsson, A.; Kogler, R.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Kutak, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.U.; Maxfield, S.J.; Mehta, A.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, M.U.; Mudrinic, M.; Muller, K.; Murin, P.; Naumann, Th.; Newman, P.R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G.D.; Pejchal, O.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Placakyte, R.; Pokorny, B.; Polifka, R.; Povh, B.; Preda, T.; Radescu, V.; Rahmat, A.J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J.E.; Rurikova, Z.; Rusakov, S.; Salek, D.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.C.; Sefkow, F.; Shaw-West, R.N.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Smiljanic, I.; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Staykova, Z.; Steder, M.; Stella, B.; Stoicea, G.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P.D.; Toll, T.; Tomasz, F.; Tran, T.H.; Traynor, D.; Trinh, T.N.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Urban, K.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; von den Driesch, M.; Wegener, D.; Wissing, Ch.; Wunsch, E.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.; Zus, R.

    2010-01-01

    Diffractive electroproduction of rho and phi mesons is measured at HERA with the H1 detector in the elastic and proton dissociative channels. The data correspond to an integrated luminosity of 51 pb^-1. About 10500 rho and 2000 phi events are analysed in the kinematic range of squared photon virtuality 2.5 < Q^2 < 60 GeV^2, photon-proton centre of mass energy 35 < W < 180 GeV and squared four-momentum transfer to the proton |t| < 3 GeV^2. The total, longitudinal and transverse cross sections are measured as a function of Q^2, W and |t|. The measurements show a transition to a dominantly "hard" behaviour, typical of high gluon densities and small q\\bar{q} dipoles, for Q^2 larger than 10 to 20 GeV^2. They support flavour independence of the diffractive exchange, expressed in terms of the scaling variable (Q^2 + M_V^2)/4, and proton vertex factorisation. The spin density matrix elements are measured as a function of kinematic variables. The ratio of the longitudinal to transverse cross sections, t...

  15. Study of Branching Fractions and CP-Violating Asymmetries in B Meson Decays to Rho And Pion Final State with the BABAR Detector

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Jinwei; /Wisconsin U., Madison

    2006-03-22

    We present measurements of branching fractions and CP-violating asymmetries in B-meson decays to {rho}{sup +}{pi}{sup 0}, {rho}{sup 0}{pi}{sup +} and {rho}{sup 0}{pi}{sup 0}. The data sample comprises 89 x 10{sup 6} {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We find the charge-averaged branching fractions {Beta}(B{sup +} {yields} {rho}{sup +}{pi}{sup 0}) = (10.9 {+-} 1.9(stat) {+-} 1.9(syst)) x 10{sup -6} and {Beta}(B{sup 0} {yields} {rho}{sup 0}{pi}{sup +}) = (9.5 {+-} 1.1 {+-} 0.9) x 10{sup -6}, and we set a 90% confidence-level upper limit {Beta}(B{sup 0} {yields} {rho}{sup 0}{pi}{sup 0}) < 2.9 x 10{sup -6}. We measure the charge asymmetries A{sub CP}{rho}{sup +}{pi}{sup 0} = 0.24 {+-} 0.16 {+-} 0.06 and {Alpha}{sub CP}{sup {rho}{sup 0}{pi}{sup +}} = -0.19 {+-} 0.11 {+-} 0.02. We also present the preliminary measurement of CP-violating asymmetries in B{sup 0} {yields} ({rho}{pi}){sup 0} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup 0} decays using a time-dependent Dalitz plot analysis. The results are obtained from a data sample of 213 million {Upsilon}(4S) {yields} B{bar B} decays, collected by the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. This analysis extends the narrow-{rho} quasi-two-body approximation used in the previous analysis, by taking into account the interference between the {rho} resonances of the three charges. We measure 16 coefficients of the bilinear form factor terms occurring in the time-dependent decay rate of the B{sup 0} meson with the use of a maximum-likelihood fit. We derive the physically relevant quantities from these coefficients. We measure the direct CP-violation parameters {Alpha}{sub {rho}{pi}} = -0.088 {+-} 0.049 {+-} 0.013 and C = 0.34 {+-} 0.11 {+-} 0.05, where the first errors are statistical and the second systematic. For the mixing-induced CP-violation parameter we find S = -0.10 {+-} 0.14 {+-} 0.04, and for the dilution and

  16. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    Science.gov (United States)

    Zhang, Xun E; Adderley, Shaquria P; Breslin, Jerome W

    2016-01-01

    Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P)-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC) or human dermal microvascular endothelial cells (HDMEC) were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER) using an electrical cell-substrate impedance sensor (ECIS). The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET) biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

  17. Activation of RhoA, but Not Rac1, Mediates Early Stages of S1P-Induced Endothelial Barrier Enhancement.

    Directory of Open Access Journals (Sweden)

    Xun E Zhang

    Full Text Available Compromised endothelial barrier function is a hallmark of inflammation. Rho family GTPases are critical in regulating endothelial barrier function, yet their precise roles, particularly in sphingosine-1-phosphate (S1P-induced endothelial barrier enhancement, remain elusive. Confluent cultures of human umbilical vein endothelial cells (HUVEC or human dermal microvascular endothelial cells (HDMEC were used to model the endothelial barrier. Barrier function was assessed by determining the transendothelial electrical resistance (TER using an electrical cell-substrate impedance sensor (ECIS. The roles of Rac1 and RhoA were tested in S1P-induced barrier enhancement. The results show that pharmacologic inhibition of Rac1 with Z62954982 failed to block S1P-induced barrier enhancement. Likewise, expression of a dominant negative form of Rac1, or knockdown of native Rac1 with siRNA, failed to block S1P-induced elevations in TER. In contrast, blockade of RhoA with the combination of the inhibitors Rhosin and Y16 significantly reduced S1P-induced increases in TER. Assessment of RhoA activation in real time using a fluorescence resonance energy transfer (FRET biosensor showed that S1P increased RhoA activation primarily at the edges of cells, near junctions. This was complemented by myosin light chain-2 phosphorylation at cell edges, and increased F-actin and vinculin near intercellular junctions, which could all be blocked with pharmacologic inhibition of RhoA. The results suggest that S1P causes activation of RhoA at the cell periphery, stimulating local activation of the actin cytoskeleton and focal adhesions, and resulting in endothelial barrier enhancement. S1P-induced Rac1 activation, however, does not appear to have a significant role in this process.

  18. Meniscal T1rho and T2 measured with 3.0T MRI increases directly after running a marathon

    Energy Technology Data Exchange (ETDEWEB)

    Stehling, Christoph [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of Muenster, Department of Clinical Radiology, Muenster (Germany); Luke, Anthony [University of California, Department of Orthopedic Surgery, San Francisco, CA (United States); Stahl, Robert [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Ludwig Maximilians University of Munich, Department of Clinical Radiology, Munich (Germany); Baum, Thomas; Joseph, Gabby; Pan, Judong; Link, Thomas M. [University of California, Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2011-06-15

    To prospectively evaluate changes in T1rho and T2 relaxation time in the meniscus using 3.0 T MRI in asymptomatic knees of marathon runners and to compare these findings with those of age-matched healthy subjects. Thirteen marathon runners underwent 3.0 T MRI including T1rho and T2 mapping sequences before, 48-72 h after, and 3 months after competition. Ten controls were examined at baseline and after 3 months. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous. and other knee abnormalities with WORMS scores. Meniscal segmentation was performed to generate T1rho and T2 maps in six compartments. No differences in morphological knee abnormalities were found before and after the marathon. However, all marathon runners showed a significant increase in T1rho and T2 values after competition in all meniscus compartments (p < 0.0001), which may indicate changes in the biochemical composition of meniscal tissue. While T2 values decreased after 3 months T1rho values remained at a high level, indicating persisting changes in the meniscal matrix composition after a marathon. T2 values in menisci have the potential to be used as biomarkers for identifying reversible meniscus matrix changes indicating potential tissue damage. T1rho values need further study, but may be a valuable marker for diagnosing early, degenerative changes in the menisci following exercise. (orig.)

  19. Gα12/13 signaling promotes cervical cancer invasion through the RhoA/ROCK-JNK signaling axis

    International Nuclear Information System (INIS)

    Yuan, Bo; Cui, Jinquan; Wang, Wuliang; Deng, Kehong

    2016-01-01

    Several reports have indicated a role for the members of the G12 family of heterotrimeric G proteins (Gα12 and Gα13) in oncogenesis and tumor cell growth. The aims of the present study were to evaluate the role of G12 signaling in cervical cancer. We demonstrated that expression of the G12 proteins was highly upregulated in cervical cancer cells. Additionally, expression of the activated forms of Gα12/Gα13 but not expression of activated Gαq induced cell invasion through the activation of the RhoA family of G proteins, but had no effect on cell proliferation in the cervical cancer cells. Inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) blocked thrombin-stimulated cell invasion, but did not inhibit cell proliferation in cervical cells, whereas the inhibition of Gαq (RGS2) had no effect. Furthermore, G12 signaling was able to activate Rho proteins, and this stimulation was inhibited by p115-RGS, and Gα12-induced invasion was blocked by an inhibitor of RhoA/B/C (C3 toxin). Pharmacological inhibition of JNK remarkably decreased G12-induced JNK activation. Both a JNK inhibitor (SP600125) and a ROCK inhibitor (Y27632) reduced G12-induced JNK and c-Jun activation, and markedly inhibited G12-induced cellular invasion. Collectively, these findings demonstrate that stimulation of G12 proteins is capable of promoting invasion through RhoA/ROCK-JNK activation. -- Highlights: •Gα12/Gα13 is upregulated in cervical cancer cell lines. •Gα12/Gα13 is not involved in cervical cancer cell proliferation. •Gα12/Gα13 promotes cervical cancer cell invasion. •The role of Rho G proteins in G12-promoted cervical cancer cell invasion. •G12 promotes cell invasion through activation of the ROCK-JNK signaling axis.

  20. The small GTPase RhoA is required to maintain spinal cord neuroepithelium organization and the neural stem cell pool

    DEFF Research Database (Denmark)

    Herzog, Dominik; Loetscher, Pirmin; van Hengel, Jolanda

    2011-01-01

    ablation. We show that, in the spinal cord neuroepithelium, RhoA is essential to localize N-cadherin and ß-catenin to AJs and maintain apical-basal polarity of neural progenitor cells. Ablation of RhoA caused the loss of AJs and severe abnormalities in the organization of cells within the neuroepithelium......Dia1), does not localize to apical AJs in which it likely stabilizes intracellular adhesion by promoting local actin polymerization and microtubule organization. Furthermore, expressing a dominant-negative form of mDia1 in neural stem/progenitor cells results in a similar phenotype compared...... with that of the RhoA conditional knock-out, namely the loss of AJs and apical polarity. Together, our data show that RhoA signaling is necessary for AJ regulation and for the maintenance of mammalian neuroepithelium organization preventing precocious cell-cycle exit and differentiation....

  1. Hydrostatic pressure promotes the proliferation and osteogenic/chondrogenic differentiation of mesenchymal stem cells: The roles of RhoA and Rac1

    Directory of Open Access Journals (Sweden)

    Yin-Hua Zhao

    2015-05-01

    Full Text Available Our previous studies have shown that hydrostatic pressure can serve as an active regulator for bone marrow mesenchymal stem cells (BMSCs. The current work further investigates the roles of cytoskeletal regulatory proteins Ras homolog gene family member A (RhoA and Ras-related C3 botulinum toxin substrate 1 (Rac1 in hydrostatic pressure-related effects on BMSCs. Flow cytometry assays showed that the hydrostatic pressure promoted cell cycle initiation in a RhoA- and Rac1-dependent manner. Furthermore, fluorescence assays confirmed that RhoA played a positive and Rac1 displayed a negative role in the hydrostatic pressure-induced F-actin stress fiber assembly. Western blots suggested that RhoA and Rac1 play central roles in the pressure-inhibited ERK phosphorylation, and Rac1 but not RhoA was involved in the pressure-promoted JNK phosphorylation. Finally, real-time polymerase chain reaction (PCR experiments showed that pressure promoted the expression of osteogenic marker genes in BMSCs at an early stage of osteogenic differentiation through the up-regulation of RhoA activity. Additionally, the PCR results showed that pressure enhanced the expression of chondrogenic marker genes in BMSCs during chondrogenic differentiation via the up-regulation of Rac1 activity. Collectively, our results suggested that RhoA and Rac1 are critical to the pressure-induced proliferation and differentiation, the stress fiber assembly, and MAPK activation in BMSCs.

  2. Hydrostatic pressure promotes the proliferation and osteogenic/chondrogenic differentiation of mesenchymal stem cells: The roles of RhoA and Rac1.

    Science.gov (United States)

    Zhao, Yin-Hua; Lv, Xin; Liu, Yan-Li; Zhao, Ying; Li, Qiang; Chen, Yong-Jin; Zhang, Min

    2015-05-01

    Our previous studies have shown that hydrostatic pressure can serve as an active regulator for bone marrow mesenchymal stem cells (BMSCs). The current work further investigates the roles of cytoskeletal regulatory proteins Ras homolog gene family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac1) in hydrostatic pressure-related effects on BMSCs. Flow cytometry assays showed that the hydrostatic pressure promoted cell cycle initiation in a RhoA- and Rac1-dependent manner. Furthermore, fluorescence assays confirmed that RhoA played a positive and Rac1 displayed a negative role in the hydrostatic pressure-induced F-actin stress fiber assembly. Western blots suggested that RhoA and Rac1 play central roles in the pressure-inhibited ERK phosphorylation, and Rac1 but not RhoA was involved in the pressure-promoted JNK phosphorylation. Finally, real-time polymerase chain reaction (PCR) experiments showed that pressure promoted the expression of osteogenic marker genes in BMSCs at an early stage of osteogenic differentiation through the up-regulation of RhoA activity. Additionally, the PCR results showed that pressure enhanced the expression of chondrogenic marker genes in BMSCs during chondrogenic differentiation via the up-regulation of Rac1 activity. Collectively, our results suggested that RhoA and Rac1 are critical to the pressure-induced proliferation and differentiation, the stress fiber assembly, and MAPK activation in BMSCs. Copyright © 2015. Published by Elsevier B.V.

  3. Longitudinal assessment of bone marrow edema-like lesions and cartilage degeneration in osteoarthritis using 3 T MR T1rho quantification

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jian [University of California, San Francisco (UCSF), Musculoskeletal and Quantitative Imaging Research (MQIR) Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Radiology Department of The Third Hospital of Hebei Medical University, Shijiazhuang (China); Li, Xiaojuan [University of California, San Francisco (UCSF), Musculoskeletal and Quantitative Imaging Research (MQIR) Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); University of California at San Francisco, Department of Radiology, San Francisco, CA (United States); Bolbos, Radu I.; Link, Thomas M.; Majumdar, Sharmila [University of California, San Francisco (UCSF), Musculoskeletal and Quantitative Imaging Research (MQIR) Group, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States)

    2010-06-15

    To quantitatively assess the relationship between bone marrow edema-like lesions (BMELs) and the associated cartilage in knee osteoarthritis (OA) using T{sub 1{rho}} quantification at 3 T MRI. Twenty-four patients with knee OA and 14 control subjects underwent 3 T MRI. Nineteen patients and all control subjects had 1-year follow-up studies. The volume and signal intensity difference of BMELs were calculated. Cartilage degeneration was graded using the cartilage subscore of Whole-Organ MRI Score (WORMS) analysis. Cartilage T{sub 1{rho}} values were calculated in each compartment as well as in cartilage overlying BMELs (OC) and surrounding cartilage (SC). At baseline, 25 BMELs were found in 16 out of 24 patients. The overall T{sub 1{rho}} values were significantly higher in patients with BMELs than in those without BMELs. At baseline and follow-up, both T{sub 1{rho}} values and WORMS cartilage subscore grading were significantly higher in OC than SC. Cartilage T{sub 1{rho}} increase from baseline to follow-up in OC was significantly higher than that in SC. An increase in T{sub 1{rho}} values in OC was correlated with signal intensity of BMEL at both baseline and follow-up, but was not correlated with BMEL volume. The results of this study suggest a local spatial correlation between BMELs and more advanced and accelerated cartilage degeneration. MRI T{sub 1{rho}} quantification in cartilage provides a sensitive tool for evaluating such correlations. (orig.)

  4. NADPH oxidase complex-derived reactive oxygen species, the actin cytoskeleton, and rho GTPases in cell migration

    DEFF Research Database (Denmark)

    Stanley, Alanna; Thompson, Kerry; Hynes, Ailish

    2014-01-01

    Abstract Significance: Rho GTPases are historically known to be central regulators of actin cytoskeleton reorganization. This affects many processes including cell migration. In addition, members of the Rac subfamily are known to be involved in reactive oxygen species (ROS) production through...... mediating cytoskeletal reorganization. Critical Issues: The role of the actin cytoskeleton in providing a scaffold for components of the Nox complex needs to be examined in the light of these new advances. During cell migration, Rho GTPases, ROS, and cytoskeletal organization appear to function as a complex...... compartments. This in conjunction with the analysis of tissues lacking specific Rho GTPases, and Nox components will facilitate a detailed examination of the interactions of these structures with the actin cytoskeleton. In combination with the analysis of ROS production, including its subcellular location...

  5. MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance.

    Science.gov (United States)

    Ogata, Takehiro; Ueyama, Tomomi; Isodono, Koji; Tagawa, Masashi; Takehara, Naofumi; Kawashima, Tsuneaki; Harada, Koichiro; Takahashi, Tomosaburo; Shioi, Tetsuo; Matsubara, Hiroaki; Oh, Hidemasa

    2008-05-01

    We identified a novel muscle-restricted putative coiled-coil protein, MURC, which is evolutionarily conserved from frog to human. MURC was localized to the cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult heart. MURC mRNA expression in the heart increased during the developmental process from the embryonic stage to adulthood. In response to pressure overload, MURC mRNA expression increased in the hypertrophied heart. Using the yeast two-hybrid system, we identified the serum deprivation response (SDPR) protein, a phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced activation of the RhoA/ROCK pathway, which modulated serum response factor-mediated atrial natriuretic peptide (ANP) expression and myofibrillar organization. SDPR augmented MURC-induced transactivation of the ANP promoter in cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC) exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction disturbances with atrial chamber enlargement, reduced thickness of the ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial fibrillation and AV block were observed in Tg-MURC mice. These findings indicate that MURC modulates RhoA signaling and that MURC plays an important role in the development of cardiac dysfunction and conduction disturbance with increased vulnerability to atrial arrhythmias.

  6. MURC, a Muscle-Restricted Coiled-Coil Protein That Modulates the Rho/ROCK Pathway, Induces Cardiac Dysfunction and Conduction Disturbance▿

    Science.gov (United States)

    Ogata, Takehiro; Ueyama, Tomomi; Isodono, Koji; Tagawa, Masashi; Takehara, Naofumi; Kawashima, Tsuneaki; Harada, Koichiro; Takahashi, Tomosaburo; Shioi, Tetsuo; Matsubara, Hiroaki; Oh, Hidemasa

    2008-01-01

    We identified a novel muscle-restricted putative coiled-coil protein, MURC, which is evolutionarily conserved from frog to human. MURC was localized to the cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult heart. MURC mRNA expression in the heart increased during the developmental process from the embryonic stage to adulthood. In response to pressure overload, MURC mRNA expression increased in the hypertrophied heart. Using the yeast two-hybrid system, we identified the serum deprivation response (SDPR) protein, a phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced activation of the RhoA/ROCK pathway, which modulated serum response factor-mediated atrial natriuretic peptide (ANP) expression and myofibrillar organization. SDPR augmented MURC-induced transactivation of the ANP promoter in cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC) exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction disturbances with atrial chamber enlargement, reduced thickness of the ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial fibrillation and AV block were observed in Tg-MURC mice. These findings indicate that MURC modulates RhoA signaling and that MURC plays an important role in the development of cardiac dysfunction and conduction disturbance with increased vulnerability to atrial arrhythmias. PMID:18332105

  7. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    Science.gov (United States)

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  8. Distinctive G Protein-Dependent Signaling by Protease-Activated Receptor 2 (PAR2 in Smooth Muscle: Feedback Inhibition of RhoA by cAMP-Independent PKA.

    Directory of Open Access Journals (Sweden)

    Wimolpak Sriwai

    Full Text Available We examined expression of protease-activated receptors 2 (PAR2 and characterized their signaling pathways in rabbit gastric muscle cells. The PAR2 activating peptide SLIGRL (PAR2-AP stimulated Gq, G13, Gi1, PI hydrolysis, and Rho kinase activity, and inhibited cAMP formation. Stimulation of PI hydrolysis was partly inhibited in cells expressing PAR2 siRNA, Gaq or Gai minigene and in cells treated with pertussis toxin, and augmented by expression of dominant negative regulator of G protein signaling (RGS4(N88S. Stimulation of Rho kinase activity was abolished by PAR-2 or Ga13 siRNA, and by Ga13 minigene. PAR2-AP induced a biphasic contraction; initial contraction was selectively blocked by the inhibitor of PI hydrolysis (U73122 or MLC kinase (ML-9, whereas sustained contraction was selectively blocked by the Rho kinase inhibitor (Y27632. PAR2-AP induced phosphorylation of MLC20, MYPT1 but not CPI-17. PAR2-AP also caused a decrease in the association of NF-kB and PKA catalytic subunit: the effect of PAR2-AP was blocked by PAR2 siRNA or phosphorylation-deficient RhoA (RhoA(S188A. PAR2-AP-induced degradation of IkBa and activation of NF-kB were abolished by the blockade of RhoA activity by Clostridium botulinum C3 exoenzyme suggesting RhoA-dependent activation of NF-kB. PAR2-AP-stimulated Rho kinase activity was significantly augmented by the inhibitors of PKA (myristoylated PKI, IKK2 (IKKIV or NF-kB (MG132, and in cells expressing dominant negative mutants of IKK (IKK(K44A, IkBa (IkBa (S32A/S36A or RhoA(S188A, suggesting feedback inhibition of Rho kinase activity via PKA derived from NF-kB pathway. PAR2-AP induced phosphorylation of RhoA and the phosphorylation was attenuated in cells expressing phosphorylation-deficient RhoA(S188A. Our results identified signaling pathways activated by PAR2 to mediate smooth muscle contraction and a novel pathway for feedback inhibition of PAR2-stimulated RhoA. The pathway involves activation of the NF-kB to

  9. The Rho GTPase Effector ROCK Regulates Cyclin A, Cyclin D1, and p27Kip1 Levels by Distinct Mechanisms

    OpenAIRE

    Croft, Daniel R.; Olson, Michael F.

    2006-01-01

    The members of the Rho GTPase family are well known for their regulation of actin cytoskeletal structures. In addition, they influence progression through the cell cycle. The RhoA and RhoC proteins regulate numerous effector proteins, with a central and vital signaling role mediated by the ROCK I and ROCK II serine/threonine kinases. The requirement for ROCK function in the proliferation of numerous cell types has been revealed by studies utilizing ROCK-selective inhibitors such as Y-27632. H...

  10. A model-based gain scheduling approach for controlling the common-rail system for GDI engines

    Science.gov (United States)

    di Gaeta, Alessandro; Montanaro, Umberto; Fiengo, Giovanni; Palladino, Angelo; Giglio, Veniero

    2012-04-01

    The progressive reduction in vehicle emission requirements have forced the automotive industry to invest in research for developing alternative and more efficient control strategies. All control features and resources are permanently active in an electronic control unit (ECU), ensuring the best performance with respect to emissions, fuel economy, driveability and diagnostics, independently from engine working point. In this article, a considerable step forward has been achieved by the common-rail technology which has made possible to vary the injection pressure over the entire engine speed range. As a consequence, the injection of a fixed amount of fuel is more precise and multiple injections in a combustion cycle can be made. In this article, a novel gain scheduling pressure controller for gasoline direct injection (GDI) engine is designed to stabilise the mean fuel pressure into the rail and to track demanded pressure trajectories. By exploiting a simple control-oriented model describing the mean pressure dynamics in the rail, the control structure turns to be simple enough to be effectively implemented in commercial ECUs. Experimental results in a wide range of operating points confirm the effectiveness of the proposed control method to tame efficiently the mean value pressure dynamics of the plant showing a good accuracy and robustness with respect to unavoidable parameters uncertainties, unmodelled dynamics, and hidden coupling terms.

  11. A critical discussion of the extraction of the {rho} - parameter at high energy hadron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Nicolescu, B. [Paris-11 Univ., 91 - Orsay (France). Inst. de Physique Nucleaire

    1996-12-31

    A new and general method is proposed for the extraction of the semi theoretical {rho}-parameter from the raw dN/dt data. By using this method it is shown that the exponential form of the hadron amplitude in the diffraction peak at high energy is doubtful and that the value {rho} = 0.135 {+-} 0.015, extracted from the very precise UA4/2 dN/dt data at {radical}s 541 GeV, is probably wrong. (author) 4 refs.

  12. Measurements of B Meson Decays to omega K* and omega rho

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.

    2005-02-14

    We describe searches for B meson decays to the charmless vector-vector final states {omega}K* and {omega}{rho} in 89 million B{bar B} pairs produced in e{sup +}e{sup -} annihilation at {radical}s = 10.58 GeV.

  13. Distinctive and selective route of PI3K/PKCα-PKCδ/RhoA-Rac1 signaling in osteoclastic cell migration.

    Science.gov (United States)

    Kim, Jin-Man; Kim, Mi Yeong; Lee, Kyunghee; Jeong, Daewon

    2016-12-05

    Cell migration during specialized stages of osteoclast precursors, mononuclear preosteoclasts, and multinucleated mature osteoclasts remain uncertain. M-CSF- and osteopontin-induced osteoclastic cell migration was inhibited by function-blocking monoclonal antibodies specific to the integrin αv and β3 subunits, suggesting that integrin αvβ3 mediates migratory signaling induced by M-CSF and osteopontin. M-CSF and osteopontin stimulation was shown to regulate two branched signaling processes, PI3K/PKCα/RhoA axis and PI3K/PKCδ/Rac1 axis. Interestingly, inactivation of RhoA or Rac1 blocked preosteoclast and mature osteoclast migration but not osteoclast precursor migration in a transwell-based cell migration assay. Moreover, the inhibitory effect on preosteoclast and mature osteoclast migration induced by Rac1 inactivation was more effective than that by RhoA inactivation. Collectively, our findings suggest that osteoclast precursor migration depends on PI3K/PKCα-PKCδ signaling mediated via integrin αvβ3 bypassing RhoA and Rac1, whereas preosteoclast and mature osteoclast migration relies on PI3K/PKCα-PKCδ/RhoA-Rac1 axis signaling mediated via integrin αvβ3 with increased dependency on PKCδ/Rac1 signaling route as differentiation progresses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Opposing roles for RhoH GTPase during T-cell migration and activation

    Science.gov (United States)

    Baker, Christina M.; Comrie, William A.; Hyun, Young-Min; Chung, Hung-Li; Fedorchuk, Christine A.; Lim, Kihong; Brakebusch, Cord; McGrath, James L.; Waugh, Richard E.; Meier-Schellersheim, Martin; Kim, Minsoo

    2012-01-01

    T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients (“go” signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition (“stop” signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1–GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1–GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4+ T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals. PMID:22689994

  15. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  16. Inactivation of the small GTP binding protein Rho induces multinucleate cell formation and apoptosis in murine T lymphoma EL4.

    Science.gov (United States)

    Moorman, J P; Bobak, D A; Hahn, C S

    1996-06-01

    The small G-protein Rho regulates the actin microfilament-dependent cytoskeleton. Exoenzyme C3 of Clostridium botulinum ADP-ribosylates Rho at Asn41, a modification that functionally inactivates Rho. Using a Sindbis virus-based transient gene expression system, we studied the role of Rho in murine EL4 T lymphoma cells. We generated a double subgenomic infectious Sindbis virus (dsSIN:C3) recombinant which expressed C3 in >95% of EL4 cells. This intracellular C3 resulted in modification and inactivation of virtually all endogenous Rho. dsSIN:C3 infection led to the formation of multinucleate cells, likely by inhibiting the actin microfilament-dependent step of cytokinesis. Intriguingly, in spite of the inhibition of cytokinesis, karyokinesis continued, with the result that cells containing a nuclear DNA content as high as 16N (eight nuclei) were observed. In addition, dsSIN:C3-mediated inactivation of Rho was a potent activator of apoptosis in EL4 cells. To discern whether the formation of multinucleate cells was responsible for the activation of apoptosis, 5-fluorouracil (5-FUra) was used to induce cell cycle arrest. As expected, EL4 cells treated with 5-FUra were prevented from forming multinucleate cells upon infection with dsSIN:C3. dsSIN:C3 infection, however, still caused marked apoptosis in 5-FUra-treated cells, indicating that this activation of apoptosis was independent of multinucleate cell formation.

  17. Signaling efficiency of Galphaq through its effectors p63RhoGEF and GEFT depends on their subcellular location

    NARCIS (Netherlands)

    Goedhart, J.; Unen, J. van; Adjobo-Hermans, M.J.W.; Gadella, T.W.

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined

  18. Induction of CTGF by TGF-β1 in normal and radiation enteritis human smooth muscle cells: Smad/Rho balance and therapeutic perspectives

    International Nuclear Information System (INIS)

    Haydont, Valerie; Mathe, Denis; Bourgier, Celine; Abdelali, Jalil; Aigueperse, Jocelyne; Bourhis, Jean; Vozenin-Brotons, Marie-Catherine

    2005-01-01

    Background and purpose: Transforming Growth Factor β1 (TGF-β1) and its downstream effector Connective Tissue Growth Factor (CTGF/CCN2), are well known fibrogenic activators and we previously showed that the Rho/ROCK pathway controls CTGF expression in intestinal smooth muscle cells isolated from patients with delayed radiation enteritis. The aim of the present work was to investigate the balance between Smad and Rho signalling pathways in the TGF-β1 CTGF induction and modulation of radiation-induced fibrogenic differentiation after addition of pravastatin, an inhibitor of Rho isoprenylation. Patients and methods: Primary human smooth muscle cells isolated from normal (N-SMC) or radiation enteritis (RE-SMC) biopsies were incubated with TGF-β1 (10 ng/ml). Induction of CTGF, as well as nucleo-cytoplasmic distribution of phospho-Smad2/3, Smad2/3 and Smad4 were analysed by Western blot and immunocytochemistry. Smad DNA binding was assessed by EMSA and Rho activation was measured by pull-down assay. Results: After TGF-β1 addition, Smads were translocated to the nucleus in both cell types. Nuclear accumulation of Smad as well as their DNA-binding activity were higher in N-SMC than in RE-SMC, whereas the opposite was observed for Rho activation, suggesting a main involvement of Rho pathway in sustained fibrogenic differentiation. This hypothesis was further supported by the antifibrotic effect observed in vitro after cell treatment with pravastatin (i.e. decreased expression of CTGF, TGF-β1 and Collagen Iα2). Conclusions: Our results suggest that TGF-β1-induced CTGF transactivation mainly depends on the Smad pathway in N-SMC, whereas in RE-SMC, Smad and Rho pathways are involved. Inhibition of Rho activity by pravastatin alters fibrogenic differentiation in vitro which opens up new therapeutic perspectives

  19. Rho-Kinase Inhibition Ameliorates Dasatinib-Induced Endothelial Dysfunction and Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Csilla Fazakas

    2018-05-01

    Full Text Available The multi-kinase inhibitor dasatinib is used for treatment of imatinib-resistant chronic myeloid leukemia, but is prone to induce microvascular dysfunction. In lung this can manifest as capillary leakage with pleural effusion, pulmonary edema or even pulmonary arterial hypertension. To understand how dasatinib causes endothelial dysfunction we examined the effects of clinically relevant concentrations of dasatinib on both human pulmonary arterial macro- and microvascular endothelial cells (ECs. The effects of dasatinib was compared to imatinib and nilotinib, two other clinically used BCR/Abl kinase inhibitors that do not inhibit Src. Real three-dimensional morphology and high resolution stiffness mapping revealed softening of both macro- and microvascular ECs upon dasatinib treatment, which was not observed in response to imatinib. In a dose-dependent manner, dasatinib decreased transendothelial electrical resistance/impedance and caused a permeability increase as well as disruption of tight adherens junctions in both cell types. In isolated perfused and ventilated rat lungs, dasatinib increased mean pulmonary arterial pressure, which was accompanied by a gain in lung weight. The Rho-kinase inhibitor Y27632 partly reversed the dasatinib-induced changes in vitro and ex vivo, presumably by acting downstream of Src. Co-administration of the Rho-kinase inhibitor Y27632 completely blunted the increased pulmonary pressure in response to dasatinib. In conclusion, a dasatinib-induced permeability increase in human pulmonary arterial macro- and microvascular ECs might explain many of the adverse effects of dasatinib in patients. Rho-kinase inhibition might be suitable to ameliorate these effects.

  20. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    International Nuclear Information System (INIS)

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  1. Anesthetic Sevoflurane Causes Rho-Dependent Filopodial Shortening in Mouse Neurons.

    Directory of Open Access Journals (Sweden)

    Jeffrey H Zimering

    Full Text Available Early postnatal anesthesia causes long-lasting learning and memory impairment in rodents, however, evidence for a specific neurotoxic effect on early synaptogenesis has not been demonstrated. Drebrin A is an actin binding protein whose localization in dendritic protrusions serves an important role in dendritic spine morphogenesis, and is a marker for early synaptogenesis. We therefore set out to investigate whether clinically-relevant concentrations of anesthetic sevoflurane, widely- used in infants and children, alters dendritic morphology in cultured fetal day 16 mouse hippocampal neurons. After 7 days in vitro, mouse hippocampal neurons were exposed to four hours of 3% sevoflurane in 95% air/5% CO2 or control condition (95% air/5% CO2. Neurons were fixed in 4% paraformaldehyde and stained with Alexa Fluor555-Phalloidin, and/or rabbit anti-mouse drebrin A/E antibodies which permitted subcellular localization of filamentous (F-actin and/or drebrin immunoreactivity, respectively. Sevoflurane caused acute significant length-shortening in filopodia and thin dendritic spines in days-in-vitro 7 neurons, an effect which was completely rescued by co-incubating neurons with ten micromolar concentrations of the selective Rho kinase inhibitor Y27632. Filopodia and thin spine recovered in length two days after sevoflurane exposure. Yet cluster-type filopodia (a precursor to synaptic filopodia were persistently significantly decreased in number on day-in-vitro 9, in part owing to preferential localization of drebrin immunoreactivity to dendritic shafts versus filopodial stalks. These data suggest that sevoflurane induces F-actin depolymerization leading to acute, reversible length-shortening in dendritic protrusions through a mechanism involving (in part activation of RhoA/Rho kinase signaling and impairs localization of drebrin A to filopodia required for early excitatory synapse formation.

  2. Constraining |V(td)|/|V(ts)| Using Radiative Penguin B -> V(K*/rho/omega)gamma Decays

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Ping; /Wisconsin U., Madison

    2006-03-08

    Exclusive radiative penguin B decays, B {yields} (K*{sup 0}/K*{sup +}) and B {yields} ({rho}/{omega}){gamma}, are flavor-changing neutral-current (FCNC) processes. Studies of these decays are of special interest in testing Standard Model (SM) predictions and searching for other beyond-the-SM FCNC interactions. Using 89 x 10{sup 6} B{bar B} pairs from BABAR, we measure the branching fraction ({Beta}), CP-asymmetry ({Alpha}), and isospin asymmetry ({Delta}{sub 0-}) of B {yields} (K*{sup 0}/K*{sup +}){gamma} as follows: {Beta}(B{sup 0} {yields} K*{sup 0}{gamma}) = 3.92 {+-} 0.20(stat.) {+-} 0.24(syst.); {Beta}(B{sup +} {yields} K*{sup +}{gamma}) = 3.87 {+-} 0.28(stat.) {+-} 0.26(syst.); {Alpha}(B {yields} K*{gamma}) = -0.013 {+-} 0.36(stat.) {+-} 0.10(syst.); {Delta}{sub 0-}(B {yields} K*{gamma}) = 0.050 {+-} 0.045(stat.) {+-} 0.028(syst.) {+-} 0.024(R{sup +/0}). The 90% confidence intervals for the CP-asymmetry and the isospin-asymmetry in the B {yields} K*{gamma} decay are given as: -0.074 < {Alpha}(B {yields} K*{gamma}) < 0.049, -0.046 < {Delta}{sub 0-} (B {yields} K*{gamma}) < 0.146. We also search for B {yields} ({rho}/{omega}){gamma} decays using 211 x 10{sup 6} B{bar B} pairs from BABAR. No evidence for these decays is found. We set the upper limits at 90% confidence level for these decays: {Beta}(B{sup 0} {yields} {rho}{sup 0}{gamma}) < 0.4 x 10{sup -6}; {Beta}(B{sup +}{yields} {rho}{sup =}{gamma}) < 1.8 x 10{sup -6}; {Beta}(B{sup 0} {yields} {omega}{gamma}) < 1.0 x 10{sup -6}; {bar {Beta}}(B {yields} ({rho}/{omega}){gamma}) < 1.2 x 10{sup -6}. These results are in good agreement with the SM predictions. The branching fractions of these decays are then used to constrain the ratio |V{sub td}|/|V{sub ts}|.

  3. Double diffractive {rho} -production in {gamma}{sup *}{gamma}{sup *} collisions

    Energy Technology Data Exchange (ETDEWEB)

    Pire, B. [Ecole Polytechnique, CPHT, Palaiseau (France); Szymanowski, L. [Soltan Institute for Nuclear Studies, Warsaw (Poland); Universite de Liege, Liege (Belgium); Wallon, S. [Universite Paris-Sud, LPT, Orsay (France)

    2005-12-01

    We present a first estimate of the cross-section for the exclusive process {gamma}{sup *}{sub L}(Q{sub 1}{sup 2}){gamma}{sup *}{sub L}(Q{sub 2}{sup 2}){yields}{rho}{sub L}{sup 0}{rho}{sub L}{sup 0}, which will be studied in the future high energy e{sup +} e{sup -}-linear collider. As a first step, we calculate the Born order approximation of the amplitude for longitudinally polarized virtual photons and mesons, in the kinematical region s >>-t, Q{sub 1}{sup 2}, Q{sub 2}{sup 2}. This process is completely calculable in the hard region Q{sub 1}{sup 2}, Q{sub 2}{sup 2}>>{lambda}{sup 2}{sub QCD}. We perform most of the steps in an analytical way. The resulting cross-section turns out to be large enough for this process to be measurable with foreseen luminosity and energy, for Q{sub 1}{sup 2} and Q{sub 2}{sup 2} in the range of a few GeV{sup 2}. (orig.)

  4. Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

    NARCIS (Netherlands)

    Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

    2016-01-01

    Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen

  5. Plant Rho-type (Rop) GTPase-dependent activation of receptor-like cytoplasmic kinases in vitro.

    Science.gov (United States)

    Dorjgotov, Dulguun; Jurca, Manuela E; Fodor-Dunai, Csilla; Szucs, Attila; Otvös, Krisztina; Klement, Eva; Bíró, Judit; Fehér, Attila

    2009-04-02

    Plants have evolved distinct mechanisms to link Rho-type (Rop) GTPases to downstream signaling pathways as compared to other eukaryotes. Here, experimental data are provided that members of the Medicago, as well as Arabidopsis, receptor-like cytoplasmic kinase family (RLCK Class VI) were strongly and specifically activated by GTP-bound Rop GTPases in vitro. Deletion analysis indicated that the residues implicated in the interaction might be distributed on various parts of the kinases. Using a chimaeric Rop GTPase protein, the importance of the Rho-insert region in kinase activation could also be verified. These data strengthen the possibility that RLCKs may serve as Rop GTPase effectors in planta.

  6. Anti-RhoC siRNAs inhibit the proliferation and invasiveness of breast cancer cells via modulating the KAI1, MMP9, and CXCR4 expression

    Directory of Open Access Journals (Sweden)

    Xu X

    2017-03-01

    Full Text Available Xu-Dong Xu,1 Han-Bin Shen,1 Li Zhu,2 Jian-Qin Lu,2 Lin Zhang,3 Zhi-Yong Luo,3 Ya-Qun Wu3 1Department of Thyroid and Breast Surgery, The Fifth Hospital of Wuhan, Hanyang District, 2Department of Oncology, 3Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China Abstract: Overexpression of RhoC in breast cancer cells indicates poor prognosis. In the present study, we aim to investigate the possible antitumor effects of anti-RhoC small-interfering RNA (siRNA in inflammatory breast cancer cells. In this study, a specific anti-RhoC siRNA was used to inhibit RhoC synthesis. Transfection of anti-RhoC siRNA into two IBC cells SUM149 and SUM190 induced extensive degradation of target mRNA and led to significant decrease in the synthesis of protein. Anti-RhoC siRNA inhibited cell proliferation and invasion, increased cell apoptosis, and induced cell cycle arrest in vitro. Moreover, the transfection of siRNA increased the expression of KAI1 and decreased the expression of MMP9 and CXCR4 in both mRNA and protein levels. Furthermore, transplantation tumor experiments in BALB/c-nu mice showed that intratumoral injection of anti-RhoC siRNA inhibited tumor growth and increased survival rate. Our results suggested that RhoC gene silencing with specific anti-RhoC siRNA would be a potential therapeutic method for metastatic breast cancer. Keywords: gene silencing, proliferation, apoptosis, cell cycle arrest

  7. RHO Mutations (p.W126L and p.A346P in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Satoshi Katagiri

    2014-01-01

    Full Text Available Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP. Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L and c.1036G>C (p.A346P, one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

  8. Engineering amount of cell-cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton

    International Nuclear Information System (INIS)

    Gray, Darren S.; Liu, Wendy F.; Shen, Colette J.; Bhadriraju, Kiran; Nelson, Celeste M.; Chen, Christopher S.

    2008-01-01

    Endothelial cell-cell contact via VE-cadherin plays an important role in regulating numerous cell functions, including proliferation. However, using different experimental approaches to manipulate cell-cell contact, investigators have observed both inhibition and stimulation of proliferation depending on the adhesive context. In this study, we used micropatterned wells combined with active positioning of cells by dielectrophoresis in order to investigate whether the number of contacting neighbors affected the proliferative response. Varying cell-cell contact resulted in a biphasic effect on proliferation; one contacting neighbor increased proliferation, while two or more neighboring cells partially inhibited this increase. We also observed that cell-cell contact increased the formation of actin stress fibers, and that expression of dominant negative RhoA (RhoN19) blocked the contact-mediated increase in stress fibers and proliferation. Furthermore, examination of heterotypic pairs of untreated cells in contact with RhoN19-expressing cells revealed that intracellular, but not intercellular, tension is required for the contact-mediated stimulation of proliferation. Moreover, engagement of VE-cadherin with cadherin-coated beads was sufficient to stimulate proliferation in the absence of actual cell-cell contact. In all, these results demonstrate that cell-cell contact signals through VE-cadherin, RhoA, and intracellular tension in the actin cytoskeleton to regulate proliferation

  9. Microfilament regulatory protein MENA increases activity of RhoA and promotes metastasis of hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Ling; Yang, Xiao-Mei; Li, Jun; Zhang, Yan-Li; Qin, Wenxin; Zhang, Zhi-Gang

    2014-09-10

    Mammalian enabled (MENA), usually known as a direct regulator of microfilament polymerization and bundling, promotes metastasis in various cancers. Here we focus on the role of MENA in hepatocellular carcinoma (HCC) metastasis and the relevant mechanism from the view of RhoA activity regulation. By HCC tissue microarray analysis, we found that MENA expression was positively associated with satellite lesions (PMENA staining in HCC tissues had significantly higher rates of early recurrence in the intermediate MENA expression group. Knockdown of MENA significantly suppressed HCC cell migration and invasion in vitro, as well as their intrahepatic and distant metastasis in vivo. Knockdown of MENA also decreased filopodia and stress fibers in SMMC-7721 cells. Furthermore, a decrease of RhoA activity was detected by a pull-down assay in SMMC-7721-shMENA cells. The ROCK inhibitor, Y-27632, suppressed migration of both MENA knockdown SMMC-7721 cells and control cells, but diminished their difference. Thus, our findings suggest that MENA promotes HCC cell motility by activating RhoA. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. ADA1 and NET1 Genes of Yeast Mediate Both Chromosome Maintenance and Mitochondrial $\\rho^{-}$ Mutagenesis

    CERN Document Server

    Koltovaya, N A; Tchekhouta, I A; Devin, A B

    2002-01-01

    An increase in the mitochondrial (mt) rho^- mutagenesis is a well-known respose of yeast cells to mutations in the numerous nuclear genes as well as to various kinds of stress. Notwithstanding the extensive studies during several decades the biological significance of this response is not yet fully understood. The genetic approach to solution of this subject includes the study of genes that are required for the high incidence of spontaneous rho^- mutants. Previously we found that mutations in certain nuclear genes including CDC28, the central cell-cycle regulation gene, may decrease the spontaneous rho^- mutability and simultaneously affect maintenance of the yeast chromosomes and plasmids. The present work provides data on identification of two more genes, resembling CDC28 in this respect. These genes NET1 and ADA1 mediate important regulatory protein-protein interactions in the yeast cell. The effects of net1 and ada1 mutations on the maintenance of yeast mt genome, chromosomes and plasmids as well as on ce...

  11. Measurement of CP-Violating Asymmetries in B0 to (rho pi)0 Using a Time-Dependent Dalitz Plot Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wu, J.

    2005-01-14

    We present the preliminary measurement of CP-violating asymmetries in B{sup 0} {yields} ({rho}{pi}){sup 0} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup 0} decays using a time-dependent Dalitz plot analysis. The results are obtained from a data sample of 213 million {Upsilon}(4S) {yields} B{bar B} decays, collected by the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. This analysis extends the narrow-rho quasi-two-body approximation used in the previous analysis, by taking into account the interference between the rho resonances of the three charges. We measure 16 coefficients of the bilinear form factor terms occurring in the time-dependent decay rate of the B{sup 0} meson with the use of a maximum-likelihood fit. We derive the physically relevant quantities from these coefficients. We measure the direct CP-violation parameters A{sub {rho}{pi}} = -0.088 {+-} 0.049 {+-} 0.013 and C = 0.34 {+-} 0.11 {+-} 0.05, where the first errors are statistical and the second systematic. For the mixing-induced CP-violation parameter we find S = -0.10 {+-} 0.14 {+-} 0.04, and for the dilution and strong phase shift parameters respectively, we obtain {Delta}C = 0.15 {+-} 0.11 {+-} 0.03 and {Delta}S = 0.22 {+-} 0.15 {+-} 0.03. For the angle alpha of the Unitarity Triangle we measure (113{sub -17}{sup +27} {+-} 6){sup o}, while only a weak constraint is achieved at the significance level of more than two standard deviations. Finally, for the relative strong phase {delta}{sub {+-}} between the B{sup 0} {yields} {rho}{sup -}{pi}{sup +} and B{sup 0} {yields} {rho}{sup +}{pi}{sup -} transitions we find (-67{sub -31}{sup +28} {+-} 7) deg, with a similarly weak constraint at two standard deviations and beyond.

  12. MicroRNA-122 triggers mesenchymal-epithelial transition and suppresses hepatocellular carcinoma cell motility and invasion by targeting RhoA.

    Directory of Open Access Journals (Sweden)

    Sheng-Chun Wang

    Full Text Available The loss of microRNA-122 (miR-122 expression is strongly associated with increased invasion and metastasis, and poor prognosis of hepatocellular carcinoma (HCC, however, the underlying mechanisms remain poorly understood. In the present study, we observed that miR-122 over-expression in HCC cell lines Sk-hep-1 and Bel-7402 triggered the mesenchymal-epithelial transition (MET, as demonstrated by epithelial-like morphological changes, up-regulated epithelial proteins (E-cadherin, ZO-1, α-catenin, occludin, BVES, and MST4, and down-regulated mesenchymal proteins (vimentin and fibronectin. The over-expression of miRNA-122 also caused cytoskeleton disruption, RhoA/Rock pathway inactivation, enhanced cell adhesion, and suppression of migration and invasion of Sk-hep-1 and Bel-7402 cells, whereas, these effects could be reversed through miR-122 inhibition. Additional studies demonstrated that the inhibition of wild-type RhoA function induced MET and inhibited cell migration and invasion, while RhoA over-expression reversed miR-122-induced MET and inhibition of migration and invasion of HCC cells, suggesting that miR-122 induced MET and suppressed the migration and invasion of HCC cells by targeting RhoA. Moreover, our results demonstrated that HNF4α up-regulated its target gene miR-122 that subsequently induced MET and inhibited cell migration and invasion, whereas miR-122 inhibition reversed these HNF4α-induced phenotypes. These results revealed functional and mechanistic links among the tumor suppressors HNF4α, miR-122, and RhoA in EMT and invasive and metastatic phenotypes of HCC. Taken together, our study provides the first evidence that the HNF4α/miR-122/RhoA axis negatively regulates EMT and the migration and invasion of HCC cells.

  13. Signaling efficiency of Gαq through its effectors p63RhoGEF and GEFT depends on their subcellular location.

    NARCIS (Netherlands)

    Goedhart, J.; van Unen, J.; Adjobo-Hermans, M.J.W.; Gadella (jr.), T.W.J.

    2013-01-01

    The p63RhoGEF and GEFT proteins are encoded by the same gene and both members of the Dbl family of guanine nucleotide exchange factors. These proteins can be activated by the heterotrimeric G-protein subunit Galphaq. We show that p63RhoGEF is located at the plasma membrane, whereas GEFT is confined

  14. Tyrosine Phosphorylation of Rac1: A Role in Regulation of Cell Spreading

    Science.gov (United States)

    Chang, Fumin; Lemmon, Christopher; Lietha, Daniel; Eck, Michael; Romer, Lewis

    2011-01-01

    Rac1 influences a multiplicity of vital cellular- and tissue-level control functions, making it an important candidate for targeted therapeutics. The activity of the Rho family member Cdc42 has been shown to be modulated by tyrosine phosphorylation at position 64. We therefore investigated consequences of the point mutations Y64F and Y64D in Rac1. Both mutations altered cell spreading from baseline in the settings of wild type, constitutively active, or dominant negative Rac1 expression, and were accompanied by differences in Rac1 targeting to focal adhesions. Rac1-Y64F displayed increased GTP-binding, increased association with βPIX, and reduced binding with RhoGDI as compared with wild type Rac1. Rac1-Y64D had less binding to PAK than Rac1-WT or Rac1-64F. In vitro assays demonstrated that Y64 in Rac1 is a target for FAK and Src. Taken together, these data suggest a mechanism for the regulation of Rac1 activity by non-receptor tyrosine kinases, with consequences for membrane extension. PMID:22163037

  15. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation

    International Nuclear Information System (INIS)

    Al-Haidari, Amr A.; Syk, Ingvar; Thorlacius, Henrik

    2014-01-01

    Highlights: • Simvastatin blocked CCL17-induced and CCR4-dependent RhoA activation in HT29 cells. • CCL17/CCR4-mediated migration of colon cancer cells was antagonised by simvastatin. • Cell migration recovered by adding Mevalonate and geranylgeranyl pyrophosphate. • Targeting HMG-CoA reductase might be useful to inhibit colon cancer metastasis. - Abstract: Background: Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects. Aim: The aim of this study was to examine the effect of simvastatin on colon cancer cell migration. Methods: Migration assays were performed to evaluate CCL17-induced colon cancer cell (HT-29) chemotaxis. In vitro tumor growth and apoptosis were assessed using a proliferation assay and annexin V assay, respectively. Active RhoA protein levels in CCL17-stimulated colon cancer cells were quantified using a G-LISA assay. Results: We found that simvastatin dose-dependently decreased CCL17-induced colon cancer cell migration. Simvastatin had no effect on colon cancer cell proliferation or apoptosis. Inhibition of beta chemokine receptor 4, CCR4, reduced CCL17-evoked activation of RhoA in colon cancer cells. Moreover, administration of mevalonate reversed the inhibitory effect of simvastatin on CCL17-induced colon cancer cell migration. Interestingly, co-incubation with geranylgeranyl pyrophosphate (GGPP) antagonized the inhibitory impact of simvastatin on colon cancer cell migration triggered by CCL17. Moreover, we observed that simvastatin decreased CCL17-induced activation of RhoA in colon cancer cells. Administration of mevalonate and GGPP reversed the inhibitory effect of simvastatin on CCL17-provoked RhoA activation in colon cancer cells. Conclusions: Taken together, our findings show for the first time that HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via

  16. The RNA-mediated, asymmetric ring regulatory mechanism of the transcription termination Rho helicase decrypted by time-resolved nucleotide analog interference probing (trNAIP).

    Science.gov (United States)

    Soares, Emilie; Schwartz, Annie; Nollmann, Marcello; Margeat, Emmanuel; Boudvillain, Marc

    2014-08-01

    Rho is a ring-shaped, ATP-dependent RNA helicase/translocase that dissociates transcriptional complexes in bacteria. How RNA recognition is coupled to ATP hydrolysis and translocation in Rho is unclear. Here, we develop and use a new combinatorial approach, called time-resolved Nucleotide Analog Interference Probing (trNAIP), to unmask RNA molecular determinants of catalytic Rho function. We identify a regulatory step in the translocation cycle involving recruitment of the 2'-hydroxyl group of the incoming 3'-RNA nucleotide by a Rho subunit. We propose that this step arises from the intrinsic weakness of one of the subunit interfaces caused by asymmetric, split-ring arrangement of primary RNA tethers around the Rho hexamer. Translocation is at highest stake every seventh nucleotide when the weak interface engages the incoming 3'-RNA nucleotide or breaks, depending on RNA threading constraints in the Rho pore. This substrate-governed, 'test to run' iterative mechanism offers a new perspective on how a ring-translocase may function or be regulated. It also illustrates the interest and versatility of the new trNAIP methodology to unveil the molecular mechanisms of complex RNA-based systems. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. T1rho and T2 relaxation times of the normal adult knee meniscus at 3T: analysis of zonal differences.

    Science.gov (United States)

    Takao, Shoichiro; Nguyen, Tan B; Yu, Hon J; Hagiwara, Shigeo; Kaneko, Yasuhito; Nozaki, Taiki; Iwamoto, Seiji; Otomo, Maki; Schwarzkopf, Ran; Yoshioka, Hiroshi

    2017-05-18

    Prior studies describe histological and immunohistochemical differences in collagen and proteoglycan content in different meniscal zones. The aim of this study is to evaluate horizontal and vertical zonal differentiation of T1rho and T2 relaxation times of the entire meniscus from volunteers without symptom and imaging abnormality. Twenty volunteers age between 19 and 38 who have no knee-related clinical symptoms, and no history of prior knee surgeries were enrolled in this study. Two T1rho mapping (b-FFE T1rho and SPGR T1rho) and T2 mapping images were acquired with a 3.0-T MR scanner. Each meniscus was divided manually into superficial and deep zones for horizontal zonal analysis. The anterior and posterior horns of each meniscus were divided manually into white, red-white and red zones for vertical zonal analysis. Zonal differences of average relaxation times among each zone, and both inter- and intra-observer reproducibility were statistically analyzed. In horizontal zonal analysis, T1rho relaxation times of the superficial zone tended to be higher than those of the deep zone, and this difference was statistically significant in the medial meniscal segments (84.3 ms vs 76.0 ms on b-FFE, p meniscus (88.4 ms vs 77.1 ms on b-FFE, p meniscus, p = 0.011). T2 relaxation times of the white zone were significantly higher than those of the red zone in the medial meniscus posterior horn (96.8 ms vs 84.3 ms, p meniscus anterior horn (104.6 ms vs 84.2 ms, p 0.74) or good (0.60-0.74) in all meniscal segments on both horizontal and vertical zonal analysis, except for inter-class correlation coefficients of the lateral meniscus on SPGR. Compared with SPGR T1rho images, b-FFE T1rho images demonstrated more significant zonal differentiation with higher inter- and intra-observer reproducibility. There are zonal differences in T1rho and T2 relaxation times of the normal meniscus.

  18. Simvastatin induces apoptosis by a Rho-dependent mechanism in cultured cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    Copaja, Miguel; Venegas, Daniel; Aranguiz, Pablo; Canales, Jimena; Vivar, Raul; Catalan, Mabel; Olmedo, Ivonne; Rodriguez, Andrea E.; Chiong, Mario; Leyton, Lisette; Lavandero, Sergio; Diaz-Araya, Guillermo

    2011-01-01

    Several clinical trials have shown the beneficial effects of statins in the prevention of coronary heart disease. Additionally, statins promote apoptosis in vascular smooth muscle cells, in renal tubular epithelial cells and also in a variety of cell lines; yet, the effects of statins on cardiac fibroblast and myofibroblast, primarily responsible for cardiac tissue healing are almost unknown. Here, we investigated the effects of simvastatin on cardiac fibroblast and myofibroblast viability and studied the molecular cell death mechanism triggered by simvastatin in both cell types. Methods: Rat neonatal cardiac fibroblasts and myofibroblasts were treated with simvastatin (0.1-10 μM) up to 72 h. Cell viability and apoptosis were evaluated by trypan blue exclusion method and by flow cytometry, respectively. Caspase-3 activation and Rho protein levels and activity were also determined by Western blot and pull-down assay, respectively. Results: Simvastatin induces caspase-dependent apoptosis of cardiac fibroblasts and myofibroblasts in a concentration- and time-dependent manner, with greater effects on fibroblasts than myofibroblasts. These effects were prevented by mevalonate, farnesylpyrophosphate and geranylgeranylpyrophosphate, but not squalene. These last results suggest that apoptosis was dependent on small GTPases of the Rho family rather than Ras. Conclusion: Simvastatin triggered apoptosis of cardiac fibroblasts and myofibroblasts by a mechanism independent of cholesterol synthesis, but dependent of isoprenilation of Rho protein. Additionally, cardiac fibroblasts were more susceptible to simvastatin-induced apoptosis than cardiac myofibroblasts. Thus simvastatin could avoid adverse cardiac remodeling leading to a less fibrotic repair of the damaged tissues. - Research Highlights: → Simvastatin decreases CF and CMF viability independent of cholesterol synthesis. → Simvastatin induces CF and CMF apoptosis in a caspase-dependent manner being CMF more resistant

  19. Fibroblast activation protein (FAP is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation.

    Directory of Open Access Journals (Sweden)

    Kuei-Min Chung

    Full Text Available BACKGROUND: The ability of human bone marrow mesenchymal stem cells (BM-MSCs to migrate and localize specifically to injured tissues is central in developing therapeutic strategies for tissue repair and regeneration. Fibroblast activation protein (FAP is a cell surface serine protease expressed at sites of tissue remodeling during embryonic development. It is also expressed in BM-MSCs, but not in normal tissues or cells. The function of FAP in BM-MSCs is not known. PRINCIPAL FINDINGS: We found that depletion of FAP proteins significantly inhibited the migration of BM-MSCs in a transwell chemotaxis assay. Such impaired migration ability of BM-MSCs could be rescued by re-expressing FAP in these cells. We then demonstrated that depletion of FAP activated intracellular RhoA GTPase. Consistently, inhibition of RhoA activity using a RhoA inhibitor rescued its migration ability. Inhibition of FAP activity with an FAP-specific inhibitor did not affect the activation of RhoA or the migration of BM-MSCs. Furthermore, the inflammatory cytokines interleukin-1beta (IL-1β and transforming growth factor-beta (TGF-β upregulated FAP expression, which coincided with better BM-MSC migration. CONCLUSIONS: Our results indicate FAP plays an important role in the migration of BM-MSCs through modulation of RhoA GTPase activity. The peptidase activity of FAP is not essential for such migration. Cytokines IL-1β and TGF-β upregulate the expression level of FAP and thus enhance BM-MSC migration.

  20. Calculation of electromagnetic rhoπ formfactor from QCD sum rules

    International Nuclear Information System (INIS)

    Eletskij, V.L.; Kogan, Ya.I.

    1982-01-01

    Electromagnetic rhoπγ form factor at intermediate momentum transfer, 0.7 GeV 2 2 2 , is calculated using QCD sum rules for the vertex function of two vector and one axial-vector currents. In this region the results obtained are consistent within 25% accuracy with the vector meson dominance model predictions and can be regarded as its theoretical ustification

  1. Inhibition of the Rho/ROCK pathway prevents neuronal degeneration in vitro and in vivo following methylmercury exposure

    International Nuclear Information System (INIS)

    Fujimura, Masatake; Usuki, Fusako; Kawamura, Miwako; Izumo, Shuji

    2011-01-01

    Methylmercury (MeHg) is an environmental neurotoxicant which induces neuropathological changes in both the central nervous and peripheral sensory nervous systems. Our recent study demonstrated that down-regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1), which is known to promote neuritic extension, preceded MeHg-induced damage in cultured cortical neurons, suggesting that MeHg-mediated axonal degeneration is due to the disturbance of neuritic extension. Therefore we hypothesized that MeHg-induced axonal degeneration might be caused by neuritic extension/retraction incoordination. This idea brought our attention to the Ras homolog gene (Rho)/Rho-associated coiled coil-forming protein kinase (ROCK) pathway because it has been known to be associated with the development of axon and apoptotic neuronal cell death. Here we show that inhibition of the Rho/ROCK pathway prevents MeHg-intoxication both in vitro and in vivo. A Rho inhibitor, C3 toxin, and 2 ROCK inhibitors, Fasudil and Y-27632, significantly protected against MeHg-induced axonal degeneration and apoptotic neuronal cell death in cultured cortical neuronal cells exposed to 100 nM MeHg for 3 days. Furthermore, Fasudil partially prevented the loss of large pale neurons in dorsal root ganglia, axonal degeneration in dorsal spinal root nerves, and vacuolar degeneration in the dorsal columns of the spinal cord in MeHg-intoxicated model rats (20 ppm MeHg in drinking water for 28 days). Hind limb crossing sign, a characteristic MeHg-intoxicated sign, was significantly suppressed in this model. The results suggest that inhibition of the Rho/ROCK pathway rescues MeHg-mediated neuritic extension/retraction incoordination and is effective for the prevention of MeHg-induced axonal degeneration and apoptotic neuronal cell death.

  2. RhoA/ROCK Signaling Pathway Mediates Shuanghuanglian Injection-Induced Pseudo-allergic Reactions.

    Science.gov (United States)

    Han, Jiayin; Zhao, Yong; Zhang, Yushi; Li, Chunying; Yi, Yan; Pan, Chen; Tian, Jingzhuo; Yang, Yifei; Cui, Hongyu; Wang, Lianmei; Liu, Suyan; Liu, Jing; Deng, Nuo; Liang, Aihua

    2018-01-01

    Background: Shuanghuanglian injection (SHLI) is a famous Chinese medicine used as an intravenous preparation for the treatment of acute respiratory tract infections. In the recent years, the immediate hypersensitivity reactions induced by SHLI have attracted broad attention. However, the mechanism involved in these reactions has not yet been elucidated. The present study aims to explore the characteristics of the immediate hypersensitivity reactions induced by SHLI and deciphers the role of the RhoA/ROCK signaling pathway in these reactions. Methods: SHLI-immunized mice or naive mice were intravenously injected (i.v.) with SHLI (600 mg/kg) once, and vascular leakage in the ears was evaluated. Passive cutaneous anaphylaxis test was conducted using sera collected from SHLI-immunized mice. Naive mice were administered (i.v.) with a single dose of 150, 300, or 600 mg/kg of SHLI, and vascular leakage, histamine release, and histopathological alterations in the ears, lungs, and intestines were tested. In vitro , human umbilical vein endothelial cell (HUVEC) monolayer was incubated with SHLI (0.05, 0.1, or 0.15 mg/mL), and the changes in endothelial permeability and cytoskeleton were observed. Western blot analysis was performed and ROCK inhibitor was employed to investigate the contribution of the RhoA/ROCK signaling pathway in SHLI-induced hypersensitivity reactions, both in HUVECs and in mice. Results: Our results indicate that SHLI was able to cause immediate dose-dependent vascular leakage, edema, and exudates in the ears, lungs, and intestines, and histamine release in mice. These were pseudo-allergic reactions, as SHLI-specific IgE was not elicited during sensitization. In addition, SHLI induced reorganization of actin cytoskeleton and disrupted the endothelial barrier. The administration of SHLI directly activated the RhoA/ROCK signaling pathway both in HUVECs and in the ears, lungs, and intestines of mice. Fasudil hydrochloride, a ROCK inhibitor, ameliorated the

  3. MR T1{rho} as an imaging biomarker for monitoring liver injury progression and regression: an experimental study in rats with carbon tetrachloride intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Feng; Wang, Yi-Xiang J.; Yuan, Jing; Deng, Min; Ahuja, Anil T. [Chinese University of Hong Kong, Department of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong SAR (China); Wong, Hing Lok [School of Public Health and Primary Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Jockey Club Centre for Osteoporosis Care and Control, Hong Kong SAR (China); Chu, Eagle S.H.; Go, Minnie Y.Y.; Yu, Jun [Chinese University of Hong Kong, Institute of Digestive Disease and Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Hong Kong SAR (China); Teng, Gao-Jun [Southeast University, Department of Radiology, Zhongda Hospital, Nanjing (China)

    2012-08-15

    Recently it was shown that the magnetic resonance imaging (MRI) T1{rho} value increased with the severity of liver fibrosis in rats with bile duct ligation. Using a rat carbon tetrachloride (CCl{sub 4}) liver injury model, this study further investigated the merit of T1{rho} relaxation for liver fibrosis evaluation. Male Sprague-Dawley rats received intraperitoneal injection of 2 ml/kg CCl{sub 4} twice weekly for up to 6 weeks. Then CCl{sub 4} was withdrawn and the animals were allowed to recover. Liver T1{rho} MRI and conventional T2-weighted images were acquired. Animals underwent MRI at baseline and at 2 days, 2 weeks, 4 weeks and 6 weeks post CCl{sub 4} injection, and they were also examined at 1 week and 4 weeks post CCl{sub 4} withdrawal. Liver histology was also sampled at these time points. Liver T1{rho} values increased slightly, though significantly, on day 2, and then increased further and were highest at week 6 post CCl{sub 4} insults. The relative liver signal intensity change on T2-weighted images followed a different time course compared with that of T1{rho}. Liver T1{rho} values decreased upon the withdrawal of the CCl{sub 4} insult. Histology confirmed the animals had typical CCl{sub 4} liver injury and fibrosis progression and regression processes. MR T1{rho} imaging can monitor CCl{sub 4}-induced liver injury and fibrosis. (orig.)

  4. A radial glia-specific role of RhoA in double cortex formation

    DEFF Research Database (Denmark)

    Cappello, Silvia; Böhringer, Christian R J; Bergami, Matteo

    2012-01-01

    disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex...

  5. Cobalt-related features of spectral and magnetic properties of RNi4Co (R=Ho, Er)

    International Nuclear Information System (INIS)

    Lukoyanov, A.V.; Knyazev, Yu.V.; Kuz‘min, Yu.I.; Kuchin, A.G.

    2014-01-01

    In this paper we investigate spectral and magnetic properties of RNi 4 Co (R=Ho, Er) intermetallics to reveal the features associated with the presence of Co substituting ion in comparison with the parent HoNi 5 and ErNi 5 compounds. Our ab initio LSDA+U calculations show that in the electronic structure Co states are strongly manifested near the Fermi energy for the case of Co in 2c position, while Co in 3g position results only in weak changes of the total DOS curve. Theoretical optical conductivity calculated assuming Co equally redistributed among 2c or 3g positions agrees well with the experimental optical conductivity. Cobalt ion in RNi 4 Co (R=Ho, Er) is characterized by magnetic moment of 1μ B that increases exchange interaction in the 3d sublattice by several times that contributes to the growth of Curie temperature in comparison with the parent compounds. - Highlights: • Electronic structure of RNi4Co (R=Ho, Er) is calculated in LSDA+U. • Cobalt ion is considered in 2c or 3g position and compared. • Experimental optical conductivity is interpreted based on the calculated one

  6. RhoA Controls Retinoid Signaling by ROCK Dependent Regulation of Retinol Metabolism

    DEFF Research Database (Denmark)

    García-Mariscal, Alberto; Peyrollier, Karine; Basse, Astrid

    2017-01-01

    The ubiquitously expressed small GTPase RhoA is essential for embryonic development and mutated in different cancers. Functionally, it is well described as a regulator of the actin cytoskeleton, but its role in gene regulation is less understood. Using primary mouse keratinocytes with a deletion ...

  7. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

    Directory of Open Access Journals (Sweden)

    Matthew J Spindler

    Full Text Available A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown.To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction.These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  8. Backward production of a spin parity 1/sup +/ rho pi enhancement at 104 GeV

    CERN Document Server

    Gavillet, P; Blokzijl, R; De van de Walle, R; Engeler, J; Ferrando, A; Foster, B; Grossman, P; Hemingway, R J; Holmgren, S O; Jongejans, B; Kittel, E W; Kluyver, J C; Lamb, P; Losty, Michael J; Marin, J C; Massaro, G G G; McDowell, W L; Montanet, Lucien; Pagiola, E; Vergeest, J; Yamdagni, N

    1977-01-01

    A spin-parity 1/sup +/ rho pi enhancement is observed for the 3 pi mass spectrum in the reaction K/sup -/p to Sigma /sup -/ pi /sup +/ pi /sup +/ pi /sup -/ where events with a small (K/sup -/ to Sigma /sup - /) momentum transfer are selected. The mass (1040 MeV) and width (230 MeV) of this enhancement are reminiscent of the A/sub 1/ to rho pi bump which has mainly been observed in the diffractive-like processes. The cross section for this enhancement at 4.15 GeV/c incident K/sup -/ momentum is (3.6+or-0.5) mu b. (16 refs).

  9. Rho GTPasas como blancos terapéuticos relevantes en cáncer y otras enfermedades humanas

    Directory of Open Access Journals (Sweden)

    Pablo Lorenzano Menna

    2010-12-01

    Full Text Available Las Rho GTPasas son una familia de proteínas clave en la transmisión de señales provenientes del exterior celular hacia efectores intracelulares tanto citoplasmáticos como nucleares. En los últimos año ha habido un desarrollo vertiginoso de múltiples herramientas genéticas y farmacológicas, lo que ha permitido establecer de manera mucho más precisa las funciones específicas de estas proteínas. El objetivo de la presente revisión es hacer foco en las múltiples funciones celulares reguladas por las Rho GTPasas, describiendo en detalle el mecanismo molecular involucrado. Se discute además la participación de estas proteínas en diversas enfermedades humanas haciendo énfasis en su vinculación con el cáncer. Por último, se hace una actualización detallada sobre las estrategias terapéuticas en experimentación que tienen a las Rho GTPasas como blancos moleculares.

  10. ADA1 and NET1 genes of yeast mediate both chromosome maintenance and mitochondrial rho- mutagenesis

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Gerasimova, A.S.; Chekhuta, I.A.; Devin, A.B.

    2002-01-01

    An increase in the mitochondrial (mt) rho - mutagenesis is a well-known response of yeast cells to mutations in the numerous nuclear genes as well as to various kinds of stress. Notwithstanding the extensive studies during several decades the biological significance of this response is not yet fully understood. The genetic approach to solution of this subject includes the study of genes that are required for the high incidence of spontaneous rho - mutants. Previously we found that mutations in certain nuclear genes including CDC28, the central cell-cycle regulation gene, may decrease the spontaneous rho - mutability and simultaneously affect maintenance of the yeast chromosomes and plasmids. The present work provides data on identification of two more genes, resembling CDC28 in this respect. These genes NET1 and ADA1 mediate important regulatory protein-protein interactions in the yeast cell. The effects of net1 and ada1 mutations on the maintenance of yeast mt genome, chromosomes and plasmids as well on cell sensitivity to ionizing radiation are also described. (author)

  11. Study of direct Cp violation in B decay into vector mesons including rho zero-omega mixing in the framework of the LHCb experiment; Etude de la violation directe de CP dans la desintegration du meson B en mesons vecteurs incluant le melange {rho}{sup 0} - {omega} dans le cadre de l'experience LHCb

    Energy Technology Data Exchange (ETDEWEB)

    Rimbault, C

    2004-02-01

    {rho}{sub 0} - {omega} mixing effect on direct CP violation in B decay into vector mesons is one of the main studies of this work. The first part is dedicated to the calculation of the decay amplitudes of the channels B {yields} V{rho}{sup 0}({omega}) which have been represented by a model. We have used the helicity formalism. In such a way branching ratios and asymmetries depending on form factor models and other parameters are predicted. Direct CP violation appears at several levels: in branching ratios, in angular distributions and in differential asymmetry as a function of {rho}{sup 0} - {omega} mass. The dominance of the longitudinal polarization in the studied channels is confirmed by Babar and Belle experimental results. We calculated too the strong phase and the ratio of Penguin to Tree amplitudes for each channel. In a second part, was developed an analysis of the channel B{sup 0} {yields} K{sup *0}{rho}{sup 0}({omega}) in the framework of LHCb experiment. It will start in 2007 and is dedicated to b flavor study and CP violation. The realistic analysis which has been performed shows that this channel is not appropriate to observe {rho}{sup 0} - {omega} mixing effect on asymmetry in LHCb, while the {rho}{sup +}{rho}{sup 0}({omega}) channel, for which we have predicted a branching ratio value confirmed by Babar and Belle, is much more promising. (author)

  12. Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

    International Nuclear Information System (INIS)

    Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.; Lee, Benhur; Moncman, Carole L.; McCann, Richard O.; Dutch, Rebecca Ellis

    2006-01-01

    The paramyxovirus fusion protein (F) promotes fusion of the viral envelope with the plasma membrane of target cells as well as cell-cell fusion. The plasma membrane is closely associated with the actin cytoskeleton, but the role of actin dynamics in paramyxovirus F-mediated membrane fusion is unclear. We examined cell-cell fusion promoted by two different paramyxovirus F proteins in three cell types in the presence of constitutively active Rho family GTPases, major cellular coordinators of actin dynamics. Reporter gene and syncytia assays demonstrated that expression of either Rac1 V12 or Cdc42 V12 could increase cell-cell fusion promoted by the Hendra or SV5 glycoproteins, though the effect was dependent on the cell type expressing the viral glycoproteins. In contrast, RhoA L63 decreased cell-cell fusion promoted by Hendra glycoproteins but had little affect on SV5 F-mediated fusion. Also, data suggested that GTPase activation in the viral glycoprotein-containing cell was primarily responsible for changes in fusion. Additionally, we found that activated Cdc42 promoted nuclear rearrangement in syncytia

  13. Comparison of T1rho imaging between spoiled gradient echo (SPGR) and balanced steady state free precession (b-FFE) sequence of knee cartilage at 3 T MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nozaki, Taiki; Kaneko, Yasuhito; Yu, Hon J. [Department of Radiological Sciences, University of California, Irvine, CA (United States); Kaneshiro, Kayleigh [School of Medicine, University of California, Irvine, CA (United States); Schwarzkopf, Ran [Department of Orthopaedic Surgery, University of California, Irvine, CA (United States); Yoshioka, Hiroshi, E-mail: hiroshi@uci.edu [Department of Radiological Sciences, University of California, Irvine, CA (United States)

    2015-07-15

    Highlights: • T1rho values on b-FFE tend to be higher than those on SPGR. • The reproducibility of T1rho cartilage segmentation is higher on SPGR than b-FFE. • There is angular variation of T1rho profiles. • Average T1rho values in the superficial layer are higher than in the deep layer. - Abstract: Purpose: To investigate the difference in T1rho profiles of the entire femoral cartilage between SPGR and b-FFE sequences at 3.0 T. Materials and methods: 20 healthy volunteers were enrolled in this study. T1rho images of each subject were acquired with two types of pulse sequences: SPGR and b-FFE. Femoral cartilage segmentation was performed by two independent raters slice-by-slice using Matlab. Inter- and intra-observer reproducibility between the two imaging protocols was calculated. The relative signal intensity (SI) of cartilage, subchondral bone marrow, joint effusion, and the relative signal contrast between structures of the knee were quantitatively measured. The difference in T1rho values between SPGR and b-FFE sequences was statistically analyzed using the Wilcoxon signed-rank test. Results: The average T1rho value of the entire femoral cartilage with b-FFE was significantly higher compared to SPGR (p < 0.05). The reproducibility of the segmented area and T1rho values was superior with SPGR compared to b-FFE. The inter-class correlation coefficient was 0.846 on SPGR and 0.824 on b-FFE. The intra-class correlation coefficient of T1rho values was 0.878 on SPGR and 0.836 on b-FFE. The two imaging techniques demonstrated different signal and contrast characteristics. The relative SI of fluid was significantly higher on SPGR, while the relative SI of subchondral bone was significantly higher on b-FFE (p < 0.001). There were also significant differences in the relative contrast between fluid–cartilage, fluid–subchondral bone, and cartilage–subchondral bone between the two sequences (all p < 0.001). Conclusion: We need to pay attention to differences in

  14. Small-Molecule Inhibition of Rho/MKL/SRF Transcription in Prostate Cancer Cells: Modulation of Cell Cycle, ER Stress, and Metastasis Gene Networks

    Directory of Open Access Journals (Sweden)

    Chris R. Evelyn

    2016-05-01

    Full Text Available Metastasis is the major cause of cancer deaths and control of gene transcription has emerged as a critical contributing factor. RhoA- and RhoC-induced gene transcription via the actin-regulated transcriptional co-activator megakaryocytic leukemia (MKL and serum response factor (SRF drive metastasis in breast cancer and melanoma. We recently identified a compound, CCG-1423, which blocks Rho/MKL/SRF-mediated transcription and inhibits PC-3 prostate cancer cell invasion. Here, we undertook a genome-wide expression study in PC-3 cells to explore the mechanism and function of this compound. There was significant overlap in the genes modulated by CCG-1423 and Latrunculin B (Lat B, which blocks the Rho/MKL/SRF pathway by preventing actin polymerization. In contrast, the general transcription inhibitor 5,6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole (DRB showed a markedly different pattern. Effects of CCG-1423 and Lat B on gene expression correlated with literature studies of MKL knock-down. Gene sets involved in DNA synthesis and repair, G1/S transition, and apoptosis were modulated by CCG-1423. It also upregulated genes involved in endoplasmic reticulum stress. Targets of the known Rho target transcription factor family E2F and genes related to melanoma progression and metastasis were strongly suppressed by CCG-1423. These results confirm the ability of our compound to inhibit expression of numerous Rho/MKL-dependent genes and show effects on stress pathways as well. This suggests a novel approach to targeting aggressive cancers and metastasis.

  15. T1rho, T{sub 2} and focal knee cartilage abnormalities in physically active and sedentary healthy subjects versus early OA patients - a 3.0-Tesla MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, Robert [University of California, San Francisco, Musculoskeletal and Quantitative Imaging Group, Department of Radiology, San Francisco, CA (United States); University Hospitals-Campus Grosshadern, Ludwig Maximilians University of Munich, Department of Clinical Radiology, Munich (Germany); Luke, Anthony; Ma, C.B. [University of California, San Francisco, Department of Orthopedic Surgery, San Francisco, CA (United States); Li, Xiaojuan; Carballido-Gamio, Julio; Majumdar, Sharmila; Link, Thomas M. [University of California, San Francisco, Musculoskeletal and Quantitative Imaging Group, Department of Radiology, San Francisco, CA (United States)

    2009-01-15

    (1) To assess the degree of focal cartilage abnormalities in physically active and sedentary healthy subjects as well as in patients with early osteoarthritis (OA). (2) To determine the diagnostic value of T2 and T1rho measurements in identifying asymptomatic physically active subjects with focal cartilage lesions. Thirteen asymptomatic physically active subjects, 7 asymptomatic sedentary subjects, and 17 patients with mild OA underwent 3.0-T MRI of the knee joint. T1rho and T2 values, cartilage volume and thickness, as well as the WORMS scores were obtained. Nine out of 13 active healthy subjects had focal cartilage abnormalities. T1rho and T2 values in active subjects with and without focal cartilage abnormalities differed significantly (p<0.05). T1rho and T2 values were significantly higher (p<0.05) in early OA patients compared to healthy subjects. T1rho measurements were superior to T2 in differentiating OA patients from healthy subjects, yet T1rho was moderately age-dependent. (1) Active subjects showed a high prevalence of focal cartilage abnormalities and (2) active subjects with and without focal cartilage abnormalities had different T1rho and T2 composition of cartilage. Thus, T1rho and T2 could be a parameter suited to identify active healthy subjects at higher risk for developing cartilage pathology. (orig.)

  16. Measurement of the e+e- → π+π-π+π- cross section in the rho'(1600) energy region

    International Nuclear Information System (INIS)

    Bacci, C.; De Zorzi, G.; Penso, G.; Stella, B.; Baldini-Celio, R.; Battistoni, G.; Capon, G.; Del Fabbro, R.; Iarocci, E.; Murtas, G.P.

    1980-01-01

    The cross section for the reaction e + e - → π + π - π + π - has been measured at the e + e - storage ring Adone, in the total c.m. energy range 1.42-2.20 GeV. The peak and the following descent of the rho'(1600) resonance is observed. Using also lower energy data, and assuming that only one resonant amplitude contributes to the observed cross section, the parameters of the rho'(1600) are deduced. (orig.)

  17. Inhibition of RhoA GTPase and the subsequent activation of PTP1B protects cultured hippocampal neurons against amyloid β toxicity

    Directory of Open Access Journals (Sweden)

    Rodriguez-Tebar Alfredo

    2011-02-01

    Full Text Available Abstract Background Amyloid beta (Aβ is the main agent responsible for the advent and progression of Alzheimer's disease. This peptide can at least partially antagonize nerve growth factor (NGF signalling in neurons, which may be responsible for some of the effects produced by Aβ. Accordingly, better understanding the NGF signalling pathway may provide clues as to how to protect neurons from the toxic effects of Aβ. Results We show here that Aβ activates the RhoA GTPase by binding to p75NTR, thereby preventing the NGF-induced activation of protein tyrosine phosphatase 1B (PTP1B that is required for neuron survival. We also show that the inactivation of RhoA GTPase and the activation of PTP1B protect cultured hippocampal neurons against the noxious effects of Aβ. Indeed, either pharmacological inhibition of RhoA with C3 ADP ribosyl transferase or the transfection of cultured neurons with a dominant negative form of RhoA protects cultured hippocampal neurons from the effects of Aβ. In addition, over-expression of PTP1B also prevents the deleterious effects of Aβ on cultured hippocampal neurons. Conclusion Our findings indicate that potentiating the activity of NGF at the level of RhoA inactivation and PTP1B activation may represent a new means to combat the noxious effects of Aβ in Alzheimer's disease.

  18. Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1.

    Science.gov (United States)

    Li, Shoushan; Yan, Ting; Deng, Rong; Jiang, Xuesong; Xiong, Huaping; Wang, Yuan; Yu, Qiao; Wang, Xiaohua; Chen, Cheng; Zhu, Yichao

    2017-01-01

    Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates. A low dose of kaempferol (20 μmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells. The low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway.

  19. The invisible hand: regulation of RHO GTPases by RHOGDIs

    OpenAIRE

    Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

    2011-01-01

    The 'invisible hand' is a term originally coined by Adam Smith in the Theory of Moral Sentiments to describe the forces of self-interest, competition, and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, u...

  20. Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.

    Science.gov (United States)

    Scarlett, Kisha A; White, El-Shaddai Z; Coke, Christopher J; Carter, Jada R; Bryant, Latoya K; Hinton, Cimona V

    2018-04-01

    G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro However, the reduced signaling entities responsible for the observed functional outputs remain elusive. This study now delineates the signaling mechanism whereby heterodimeric association between CXCR4 and CB2, induced by simultaneous agonist treatment, results in decreased CXCR4-mediated cell migration, invasion, and adhesion through inhibition of the Gα13/RhoA signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates Gα13 (GNA13), and subsequently, the small GTPase RhoA, which is required for directional cell migration and the metastatic potential of cancer cells. These studies in prostate cancer cells demonstrate decreased protein expression levels of Gα13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation. Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal rearrangement resulting in the attenuation of cell migration and invasion of an endothelial cell barrier. Finally, a reduction was observed in the expression of integrin α5 (ITGA5) upon heterodimerization, supported by decreased cell adhesion to extracellular matrices in vitro Taken together, the data identify a novel pharmacologic mechanism for the modulation of tumor cell migration and invasion in the context of metastatic disease. Implications: This study investigates a signaling mechanism by which GPCR heterodimerization inhibits cancer cell migration. Mol Cancer Res; 16(4); 728-39. ©2018 AACR . ©2018 American Association for Cancer Research.

  1. The rho'(1600) in the reaction γp->π+π-π0π0p at photon energies of 20-70 GeV

    International Nuclear Information System (INIS)

    Atkinson, M.; Davenport, M.; Flower, P.; Hutton, J.S.; Kumar, B.R.; Morris, J.A.G.; Morris, J.V.; Sharp, P.H.; Bussey, P.J.; Dainton, J.B.; Paterson, C.; Raine, C.; Skillicorn, I.O.; Smith, K.M.; Brodbeck, T.J.; Clegg, A.B.; Flynn, P.J.; Henderson, R.C.W.; Newton, D.; Axon, T.J.; Barberis, D.; Dickinson, B.; Donnachie, A.; Ellison, R.J.; Hughes-Jones, R.E.; Ibbotson, M.; Lafferty, G.D.; Lane, J.B.; Mercer, D.; Thompson, R.J.; Waite, A.P.; Worsell, M.F.; Laberrigue, J.; Levy, J.M.; Vaissiere, C. de la; Yiou, T.P.; Brookes, G.R.; Bunn, J.J.; Galbraith, W.; McClatchey, R.

    1985-01-01

    The reaction γp->π + π - π 0 π 0 p (excluding ωπ 0 production) has been studied for photon energies in the range 20-70 GeV. A peak is seen in the 4π mass spectrum at proportional1.66 GeV with a width of proportional0.3 GeV which is identified with the rho'(1600). Maximum likelihood fits show that the peak is dominantly in rhosup(+-)πsup(-+)π 0 with B(rho'->rho 0 π 0 π 0 )/(Brho'->rhosup(+-)πsup(-+)π 0 ) 1 or π'. (orig.)

  2. Nature of extracellular signal that triggers RhoA/ROCK activation for the basal internal anal sphincter tone in humans

    Science.gov (United States)

    Singh, Jagmohan; Kumar, Sumit; Phillips, Benjamin

    2015-01-01

    The extracellular signal that triggers activation of rho-associated kinase (RhoA/ROCK), the major molecular determinant of basal internal anal sphincter (IAS) smooth muscle tone, is not known. Using human IAS tissues, we identified the presence of the biosynthetic machineries for angiotensin II (ANG II), thromboxane A2 (TXA2), and prostaglandin F2α (PGF2α). These end products of the renin-angiotensin system (RAS) (ANG II) and arachidonic acid (TXA2 and PGF2α) pathways and their effects in human IAS vs. rectal smooth muscle (RSM) were studied. A multipronged approach utilizing immunocytochemistry, Western blot analyses, and force measurements was implemented. Additionally, in a systematic analysis of the effects of respective inhibitors along different steps of biosynthesis and those of antagonists, their end products were evaluated either individually or in combination. To further describe the molecular mechanism for the IAS tone via these pathways, we monitored RhoA/ROCK activation and its signal transduction cascade. Data showed characteristically higher expression of biosynthetic machineries of RAS and AA pathways in the IAS compared with the RSM. Additionally, specific inhibition of the arachidonic acid (AA) pathway caused ∼80% decrease in the IAS tone, whereas that of RAS lead to ∼20% decrease. Signal transduction studies revealed that the end products of both AA and RAS pathways cause increase in the IAS tone via activation of RhoA/ROCK. Both AA and RAS (via the release of their end products TXA2, PGF2α, and ANG II, respectively), provide extracellular signals which activate RhoA/ROCK for the maintenance of the basal tone in human IAS. PMID:25882611

  3. Activation of rho is involved in the mechanism of hydrogen-peroxide-induced lung edema in isolated perfused rabbit lung.

    Science.gov (United States)

    Chiba, Y; Ishii, Y; Kitamura, S; Sugiyama, Y

    2001-09-01

    Acute lung injury is attributed primarily to increased vascular permeability caused by reactive oxygen species derived from neutrophils, such as hydrogen peroxide (H2O2). Increased permeability is accompanied by the contraction and cytoskeleton reorganization of endothelial cells, resulting in intercellular gap formation. The Rho family of Ras-like GTPases is implicated in the regulation of the cytoskeleton and cell contraction. We examined the role of Rho in H2O2-induced pulmonary edema with the use of isolated perfused rabbit lungs. To our knowledge, this is the first study to examine the role of Rho in increased vascular permeability induced by H2O2 in perfused lungs. Vascular permeability was evaluated on the basis of the capillary filtration coefficient (Kfc, ml/min/cm H2O/100 g). We found that H2O2 (300 microM) increased lung weight, Kfc, and pulmonary capillary pressure. These effects of H2O2 were abolished by treatment with Y-27632 (50 microM), an inhibitor of the Rho effector p160 ROCK. In contrast, the muscular relaxant papaverine inhibited the H2O2-induced rise in pulmonary capillary pressure, but did not suppress the increases in lung weight and Kfc. These findings indicate that H2O2 causes pulmonary edema by elevating hydrostatic pressure and increasing vascular permeability. Y-27632 inhibited the formation of pulmonary edema by blocking both of these H2O2-induced effects. Our results suggest that Rho-related pathways have a part in the mechanism of H2O2-induced pulmonary edema. Copyright 2001 Academic Press.

  4. Production of the $\\rho(770)^{0}$ meson in pp and Pb–Pb collisions at $\\sqrt{s_{NN}}$ = 2.76 TeV

    CERN Document Server

    Acharya, Shreyasi; The ALICE collaboration; Adamova, Dagmar; Adolfsson, Jonatan; Aggarwal, Madan Mohan; Aglieri Rinella, Gianluca; Agnello, Michelangelo; Agrawal, Neelima; Ahammed, Zubayer; Ahn, Sang Un; Aiola, Salvatore; Akindinov, Alexander; Al-turany, Mohammad; Alam, Sk Noor; Silva De Albuquerque, Danilo; Aleksandrov, Dmitry; Alessandro, Bruno; Alfaro Molina, Jose Ruben; Ali, Yasir; Alici, Andrea; Alkin, Anton; Alme, Johan; Alt, Torsten; Altenkamper, Lucas; Altsybeev, Igor; Andrei, Cristian; Andreou, Dimitra; Andrews, Harry Arthur; Andronic, Anton; Angeletti, Massimo; Anguelov, Venelin; Anson, Christopher Daniel; Anticic, Tome; Antinori, Federico; Antonioli, Pietro; Anwar, Rafay; Apadula, Nicole; Aphecetche, Laurent Bernard; Appelshaeuser, Harald; Arcelli, Silvia; Arnaldi, Roberta; Arnold, Oliver Werner; Arsene, Ionut Cristian; Arslandok, Mesut; Audurier, Benjamin; Augustinus, Andre; Averbeck, Ralf Peter; Azmi, Mohd Danish; Badala, Angela; Baek, Yong Wook; Bagnasco, Stefano; Bailhache, Raphaelle Marie; Bala, Renu; Baldisseri, Alberto; Ball, Markus; Baral, Rama Chandra; Barbano, Anastasia Maria; Barbera, Roberto; Barile, Francesco; Barioglio, Luca; Barnafoldi, Gergely Gabor; Barnby, Lee Stuart; Ramillien Barret, Valerie; Bartalini, Paolo; Barth, Klaus; Bartsch, Esther; Bastid, Nicole; Basu, Sumit; Batigne, Guillaume; Batyunya, Boris; Batzing, Paul Christoph; Bazo Alba, Jose Luis; Bearden, Ian Gardner; Beck, Hans; Bedda, Cristina; Behera, Nirbhay Kumar; Belikov, Iouri; Bellini, Francesca; Bello Martinez, Hector; Bellwied, Rene; Espinoza Beltran, Lucina Gabriela; Belyaev, Vladimir; Bencedi, Gyula; Beole, Stefania; Bercuci, Alexandru; Berdnikov, Yaroslav; Berenyi, Daniel; Bertens, Redmer Alexander; Berzano, Dario; Betev, Latchezar; Bhaduri, Partha Pratim; Bhasin, Anju; Bhat, Inayat Rasool; Bhatt, Himani; Bhattacharjee, Buddhadeb; Bhom, Jihyun; Bianchi, Antonio; Bianchi, Livio; Bianchi, Nicola; Bielcik, Jaroslav; Bielcikova, Jana; Bilandzic, Ante; Biro, Gabor; Biswas, Rathijit; Biswas, Saikat; Blair, Justin Thomas; Blau, Dmitry; Blume, Christoph; Boca, Gianluigi; Bock, Friederike; Bogdanov, Alexey; Boldizsar, Laszlo; Bombara, Marek; Bonomi, Germano; Bonora, Matthias; Borel, Herve; Borissov, Alexander; Borri, Marcello; Botta, Elena; Bourjau, Christian; Bratrud, Lars; Braun-munzinger, Peter; Bregant, Marco; Broker, Theo Alexander; Broz, Michal; Brucken, Erik Jens; Bruna, Elena; Bruno, Giuseppe Eugenio; Budnikov, Dmitry; Buesching, Henner; Bufalino, Stefania; Buhler, Paul; Buncic, Predrag; Busch, Oliver; Buthelezi, Edith Zinhle; Bashir Butt, Jamila; Buxton, Jesse Thomas; Cabala, Jan; Caffarri, Davide; Caines, Helen Louise; Caliva, Alberto; Calvo Villar, Ernesto; Soto Camacho, Rabi; Camerini, Paolo; Capon, Aaron Allan; Carena, Francesco; Carena, Wisla; Carnesecchi, Francesca; Castillo Castellanos, Javier Ernesto; Castro, Andrew John; Casula, Ester Anna Rita; Ceballos Sanchez, Cesar; Chandra, Sinjini; Chang, Beomsu; Chang, Wan; Chapeland, Sylvain; Chartier, Marielle; Chattopadhyay, Subhasis; Chattopadhyay, Sukalyan; Chauvin, Alex; Cheshkov, Cvetan Valeriev; Cheynis, Brigitte; Chibante Barroso, Vasco Miguel; Dobrigkeit Chinellato, David; Cho, Soyeon; Chochula, Peter; Chowdhury, Tasnuva; Christakoglou, Panagiotis; Christensen, Christian Holm; Christiansen, Peter; Chujo, Tatsuya; Chung, Suh-urk; Cicalo, Corrado; Cifarelli, Luisa; Cindolo, Federico; Cleymans, Jean Willy Andre; Colamaria, Fabio Filippo; Colella, Domenico; Collu, Alberto; Colocci, Manuel; Concas, Matteo; Conesa Balbastre, Gustavo; Conesa Del Valle, Zaida; Contreras Nuno, Jesus Guillermo; Cormier, Thomas Michael; Corrales Morales, Yasser; Cortese, Pietro; Cosentino, Mauro Rogerio; Costa, Filippo; Costanza, Susanna; Crkovska, Jana; Crochet, Philippe; Cuautle Flores, Eleazar; Cunqueiro Mendez, Leticia; Dahms, Torsten; Dainese, Andrea; Danisch, Meike Charlotte; Danu, Andrea; Das, Debasish; Das, Indranil; Das, Supriya; Dash, Ajay Kumar; Dash, Sadhana; De, Sudipan; De Caro, Annalisa; De Cataldo, Giacinto; De Conti, Camila; De Cuveland, Jan; De Falco, Alessandro; De Gruttola, Daniele; De Marco, Nora; De Pasquale, Salvatore; Derradi De Souza, Rafael; Franz Degenhardt, Hermann; Deisting, Alexander; Deloff, Andrzej; Delsanto, Silvia; Deplano, Caterina; Dhankher, Preeti; Di Bari, Domenico; Di Mauro, Antonio; Di Ruzza, Benedetto; Arteche Diaz, Raul; Dietel, Thomas; Dillenseger, Pascal; Ding, Yanchun; Divia, Roberto; Djuvsland, Oeystein; Dobrin, Alexandru Florin; Domenicis Gimenez, Diogenes; Donigus, Benjamin; Dordic, Olja; Van Doremalen, Lennart Vincent; Dubey, Anand Kumar; Dubla, Andrea; Ducroux, Laurent; Dudi, Sandeep; Duggal, Ashpreet Kaur; Dukhishyam, Mallick; Dupieux, Pascal; Ehlers Iii, Raymond James; Elia, Domenico; Endress, Eric; Engel, Heiko; Epple, Eliane; Erazmus, Barbara Ewa; Erhardt, Filip; Ersdal, Magnus Rentsch; Espagnon, Bruno; Eulisse, Giulio; Eum, Jongsik; Evans, David; Evdokimov, Sergey; Fabbietti, Laura; Faggin, Mattia; Faivre, Julien; Fantoni, Alessandra; Fasel, Markus; Feldkamp, Linus; Feliciello, Alessandro; Feofilov, Grigorii; Fernandez Tellez, Arturo; Ferretti, Alessandro; Festanti, Andrea; Feuillard, Victor Jose Gaston; Figiel, Jan; Araujo Silva Figueredo, Marcel; Filchagin, Sergey; Finogeev, Dmitry; Fionda, Fiorella; Fiorenza, Gabriele; Floris, Michele; Foertsch, Siegfried Valentin; Foka, Panagiota; Fokin, Sergey; Fragiacomo, Enrico; Francescon, Andrea; Francisco, Audrey; Frankenfeld, Ulrich Michael; Fronze, Gabriele Gaetano; Fuchs, Ulrich; Furget, Christophe; Furs, Artur; Fusco Girard, Mario; Gaardhoeje, Jens Joergen; Gagliardi, Martino; Gago Medina, Alberto Martin; Gajdosova, Katarina; Gallio, Mauro; Duarte Galvan, Carlos; Ganoti, Paraskevi; Garabatos Cuadrado, Jose; Garcia-solis, Edmundo Javier; Garg, Kunal; Gargiulo, Corrado; Gasik, Piotr Jan; Gauger, Erin Frances; De Leone Gay, Maria Beatriz; Germain, Marie; Ghosh, Jhuma; Ghosh, Premomoy; Ghosh, Sanjay Kumar; Gianotti, Paola; Giubellino, Paolo; Giubilato, Piero; Glassel, Peter; Gomez Coral, Diego Mauricio; Gomez Ramirez, Andres; Gonzalez, Victor; Gonzalez Zamora, Pedro; Gorbunov, Sergey; Gorlich, Lidia Maria; Gotovac, Sven; Grabski, Varlen; Graczykowski, Lukasz Kamil; Graham, Katie Leanne; Greiner, Leo Clifford; Grelli, Alessandro; Grigoras, Costin; Grigoryev, Vladislav; Grigoryan, Ara; Grigoryan, Smbat; Gronefeld, Julius Maximilian; Grosa, Fabrizio; Grosse-oetringhaus, Jan Fiete; Grosso, Raffaele; Guernane, Rachid; Guerzoni, Barbara; Guittiere, Manuel; Gulbrandsen, Kristjan Herlache; Gunji, Taku; Gupta, Anik; Gupta, Ramni; Bautista Guzman, Irais; Haake, Rudiger; Habib, Michael Karim; Hadjidakis, Cynthia Marie; Hamagaki, Hideki; Hamar, Gergoe; Hamon, Julien Charles; Hannigan, Ryan; Haque, Md Rihan; Harris, John William; Harton, Austin Vincent; Hassan, Hadi; Hatzifotiadou, Despina; Hayashi, Shinichi; Heckel, Stefan Thomas; Hellbar, Ernst; Helstrup, Haavard; Herghelegiu, Andrei Ionut; Gonzalez Hernandez, Emma; Herrera Corral, Gerardo Antonio; Herrmann, Florian; Hetland, Kristin Fanebust; Hilden, Timo Eero; Hillemanns, Hartmut; Hills, Christopher; Hippolyte, Boris; Hohlweger, Bernhard; Horak, David; Hornung, Sebastian; Hosokawa, Ritsuya; Hristov, Peter Zahariev; Hughes, Charles; Huhn, Patrick; Humanic, Thomas; Hushnud, Hushnud; Hussain, Nur; Hussain, Tahir; Hutter, Dirk; Hwang, Dae Sung; Iddon, James Philip; Iga Buitron, Sergio Arturo; Ilkaev, Radiy; Inaba, Motoi; Ippolitov, Mikhail; Islam, Md Samsul; Ivanov, Marian; Ivanov, Vladimir; Izucheev, Vladimir; Jacak, Barbara; Jacazio, Nicolo; Jacobs, Peter Martin; Jadhav, Manoj Bhanudas; Jadlovska, Slavka; Jadlovsky, Jan; Jaelani, Syaefudin; Jahnke, Cristiane; Jakubowska, Monika Joanna; Janik, Malgorzata Anna; Jena, Chitrasen; Jercic, Marko; Jimenez Bustamante, Raul Tonatiuh; Jin, Muqing; Jones, Peter Graham; Jusko, Anton; Kalinak, Peter; Kalweit, Alexander Philipp; Kang, Ju Hwan; Kaplin, Vladimir; Kar, Somnath; Karasu Uysal, Ayben; Karavichev, Oleg; Karavicheva, Tatiana; Karczmarczyk, Przemyslaw; Karpechev, Evgeny; Kebschull, Udo Wolfgang; Keidel, Ralf; Keijdener, Darius Laurens; Keil, Markus; Ketzer, Bernhard Franz; Khabanova, Zhanna; Khan, Shaista; Khan, Shuaib Ahmad; Khanzadeev, Alexei; Kharlov, Yury; Khatun, Anisa; Khuntia, Arvind; Kielbowicz, Miroslaw Marek; Kileng, Bjarte; Kim, Byungchul; Kim, Daehyeok; Kim, Dong Jo; Kim, Eun Joo; Kim, Hyeonjoong; Kim, Jinsook; Kim, Jiyoung; Kim, Minjung; Kim, Se Yong; Kim, Taejun; Kim, Taesoo; Kirsch, Stefan; Kisel, Ivan; Kiselev, Sergey; Kisiel, Adam Ryszard; Klay, Jennifer Lynn; Klein, Carsten; Klein, Jochen; Klein-boesing, Christian; Klewin, Sebastian; Kluge, Alexander; Knichel, Michael Linus; Knospe, Anders Garritt; Kobdaj, Chinorat; Varga-kofarago, Monika; Kohler, Markus Konrad; Kollegger, Thorsten; Kondratyeva, Natalia; Kondratyuk, Evgeny; Konevskikh, Artem; Konyushikhin, Maxim; Kovalenko, Oleksandr; Kovalenko, Vladimir; Kowalski, Marek; Kralik, Ivan; Kravcakova, Adela; Kreis, Lukas; Krivda, Marian; Krizek, Filip; Kruger, Mario; Kryshen, Evgeny; Krzewicki, Mikolaj; Kubera, Andrew Michael; Kucera, Vit; Kuhn, Christian Claude; Kuijer, Paulus Gerardus; Kumar, Jitendra; Kumar, Lokesh; Kumar, Shyam; Kundu, Sourav; Kurashvili, Podist; Kurepin, Alexander; Kurepin, Alexey; Kuryakin, Alexey; Kushpil, Svetlana; Kweon, Min Jung; Kwon, Youngil; La Pointe, Sarah Louise; La Rocca, Paola; Lai, Yue Shi; Lakomov, Igor; Langoy, Rune; Lapidus, Kirill; Lara Martinez, Camilo Ernesto; Lardeux, Antoine Xavier; Larionov, Pavel; Lattuca, Alessandra; Laudi, Elisa; Lavicka, Roman; Lea, Ramona; Leardini, Lucia; Lee, Seongjoo; Lehas, Fatiha; Lehner, Sebastian; Lehrbach, Johannes; Lemmon, Roy Crawford; Leogrande, Emilia; Leon Monzon, Ildefonso; Levai, Peter; Li, Xiaomei; Li, Xing Long; Lien, Jorgen Andre; Lietava, Roman; Lim, Bong-hwi; Lindal, Svein; Lindenstruth, Volker; Lindsay, Scott William; Lippmann, Christian; Lisa, Michael Annan; Litichevskyi, Vladyslav; Liu, Alwina; Ljunggren, Hans Martin; Llope, William; Lodato, Davide Francesco; Loginov, Vitaly; Loizides, Constantinos; Loncar, Petra; Lopez, Xavier Bernard; Lopez Torres, Ernesto; Lowe, Andrew John; Luettig, Philipp Johannes; Luhder, Jens Robert; Lunardon, Marcello; Luparello, Grazia; Lupi, Matteo; Maevskaya, Alla; Mager, Magnus; Mahmood, Sohail Musa; Maire, Antonin; Majka, Richard Daniel; Malaev, Mikhail; Malinina, Liudmila; Mal'kevich, Dmitry; Malzacher, Peter; Mamonov, Alexander; Manko, Vladislav; Manso, Franck; Manzari, Vito; Mao, Yaxian; Marchisone, Massimiliano; Mares, Jiri; Margagliotti, Giacomo Vito; Margotti, Anselmo; Margutti, Jacopo; Marin, Ana Maria; Markert, Christina; Marquard, Marco; Martin, Nicole Alice; Martinengo, Paolo; Martinez Hernandez, Mario Ivan; Martinez-garcia, Gines; Martinez Pedreira, Miguel; Masciocchi, Silvia; Masera, Massimo; Masoni, Alberto; Massacrier, Laure Marie; Masson, Erwann; Mastroserio, Annalisa; Mathis, Andreas Michael; Toledo Matuoka, Paula Fernanda; Matyja, Adam Tomasz; Mayer, Christoph; Mazzilli, Marianna; Mazzoni, Alessandra Maria; Meddi, Franco; Melikyan, Yuri; Menchaca-rocha, Arturo Alejandro; Meninno, Elisa; Mercado-perez, Jorge; Meres, Michal; Soncco Meza, Carlos; Mhlanga, Sibaliso; Miake, Yasuo; Micheletti, Luca; Mieskolainen, Matti Mikael; Mihaylov, Dimitar Lubomirov; Mikhaylov, Konstantin; Mischke, Andre; Mishra, Aditya Nath; Miskowiec, Dariusz Czeslaw; Mitra, Jubin; Mitu, Ciprian Mihai; Mohammadi, Naghmeh; Mohanty, Auro Prasad; Mohanty, Bedangadas; Khan, Mohammed Mohisin; Moreira De Godoy, Denise Aparecida; Perez Moreno, Luis Alberto; Moretto, Sandra; Morreale, Astrid; Morsch, Andreas; Muccifora, Valeria; Mudnic, Eugen; Muhlheim, Daniel Michael; Muhuri, Sanjib; Mukherjee, Maitreyee; Mulligan, James Declan; Gameiro Munhoz, Marcelo; Munning, Konstantin; Arratia Munoz, Miguel Ignacio; Munzer, Robert Helmut; Murakami, Hikari; Murray, Sean; Musa, Luciano; Musinsky, Jan; Myers, Corey James; Myrcha, Julian Wojciech; Naik, Bharati; Nair, Rahul; Nandi, Basanta Kumar; Nania, Rosario; Nappi, Eugenio; Narayan, Amrendra; Naru, Muhammad Umair; Nassirpour, Adrian Fereydon; Ferreira Natal Da Luz, Pedro Hugo; Nattrass, Christine; Rosado Navarro, Sebastian; Nayak, Kishora; Nayak, Ranjit; Nayak, Tapan Kumar; Nazarenko, Sergey; Negrao De Oliveira, Renato Aparecido; Nellen, Lukas; Nesbo, Simon Voigt; Neskovic, Gvozden; Ng, Fabian; Nicassio, Maria; Niedziela, Jeremi; Nielsen, Borge Svane; Nikolaev, Sergey; Nikulin, Sergey; Nikulin, Vladimir; Noferini, Francesco; Nomokonov, Petr; Nooren, Gerardus; Cabanillas Noris, Juan Carlos; Norman, Jaime; Nyanin, Alexander; Nystrand, Joakim Ingemar; Oh, Hoonjung; Ohlson, Alice Elisabeth; Oleniacz, Janusz; Oliveira Da Silva, Antonio Carlos; Oliver, Michael Henry; Onderwaater, Jacobus; Oppedisano, Chiara; Orava, Risto; Oravec, Matej; Ortiz Velasquez, Antonio; Oskarsson, Anders Nils Erik; Otwinowski, Jacek Tomasz; Oyama, Ken; Pachmayer, Yvonne Chiara; Pacik, Vojtech; Pagano, Davide; Paic, Guy; Palni, Prabhakar; Pan, Jinjin; Pandey, Ashutosh Kumar; Panebianco, Stefano; Papikyan, Vardanush; Pareek, Pooja; Park, Jonghan; Parkkila, Jasper Elias; Parmar, Sonia; Passfeld, Annika; Pathak, Surya Prakash; Patra, Rajendra Nath; Paul, Biswarup; Pei, Hua; Peitzmann, Thomas; Peng, Xinye; Pereira, Luis Gustavo; Pereira Da Costa, Hugo Denis Antonio; Peresunko, Dmitry Yurevich; Perez Lezama, Edgar; Peskov, Vladimir; Pestov, Yury; Petracek, Vojtech; Petrovici, Mihai; Petta, Catia; Peretti Pezzi, Rafael; Piano, Stefano; Pikna, Miroslav; Pillot, Philippe; Ozelin De Lima Pimentel, Lais; Pinazza, Ombretta; Pinsky, Lawrence; Pisano, Silvia; Piyarathna, Danthasinghe; Ploskon, Mateusz Andrzej; Planinic, Mirko; Pliquett, Fabian; Pluta, Jan Marian; Pochybova, Sona; Podesta Lerma, Pedro Luis Manuel; Poghosyan, Martin; Polishchuk, Boris; Poljak, Nikola; Poonsawat, Wanchaloem; Pop, Amalia; Poppenborg, Hendrik; Porteboeuf, Sarah Julie; Pozdniakov, Valeriy; Prasad, Sidharth Kumar; Preghenella, Roberto; Prino, Francesco; Pruneau, Claude Andre; Pshenichnov, Igor; Puccio, Maximiliano; Punin, Valery; Putschke, Jorn Henning; Raha, Sibaji; Rajput, Sonia; Rak, Jan; Rakotozafindrabe, Andry Malala; Ramello, Luciano; Rami, Fouad; Raniwala, Rashmi; Raniwala, Sudhir; Rasanen, Sami Sakari; Rascanu, Bogdan Theodor; Ratza, Viktor; Ravasenga, Ivan; Read, Kenneth Francis; Redlich, Krzysztof; Rehman, Attiq Ur; Reichelt, Patrick Simon; Reidt, Felix; Ren, Xiaowen; Renfordt, Rainer Arno Ernst; Reshetin, Andrey; Revol, Jean-pierre; Reygers, Klaus Johannes; Riabov, Viktor; Richert, Tuva Ora Herenui; Richter, Matthias Rudolph; Riedler, Petra; Riegler, Werner; Riggi, Francesco; Ristea, Catalin-lucian; Rode, Sudhir Pandurang; Rodriguez Cahuantzi, Mario; Roeed, Ketil; Rogalev, Roman; Rogochaya, Elena; Rohr, David Michael; Roehrich, Dieter; Rokita, Przemyslaw Stefan; Ronchetti, Federico; Dominguez Rosas, Edgar; Roslon, Krystian; Rosnet, Philippe; Rossi, Andrea; Rotondi, Alberto; Roukoutakis, Filimon; Roy, Christelle Sophie; Roy, Pradip Kumar; Vazquez Rueda, Omar; Rui, Rinaldo; Rumyantsev, Boris; Rustamov, Anar; Ryabinkin, Evgeny; Ryabov, Yury; Rybicki, Andrzej; Saarinen, Sampo; Sadhu, Samrangy; Sadovskiy, Sergey; Safarik, Karel; Saha, Sumit Kumar; Sahoo, Baidyanath; Sahoo, Pragati; Sahoo, Raghunath; Sahoo, Sarita; Sahu, Pradip Kumar; Saini, Jogender; Sakai, Shingo; Saleh, Mohammad Ahmad; Sambyal, Sanjeev Singh; Samsonov, Vladimir; Sandoval, Andres; Sarkar, Amal; Sarkar, Debojit; Sarkar, Nachiketa; Sarma, Pranjal; Sas, Mike Henry Petrus; Scapparone, Eugenio; Scarlassara, Fernando; Schaefer, Brennan; Scheid, Horst Sebastian; Schiaua, Claudiu Cornel; Schicker, Rainer Martin; Schmidt, Christian Joachim; Schmidt, Hans Rudolf; Schmidt, Marten Ole; Schmidt, Martin; Schmidt, Nicolas Vincent; Schukraft, Jurgen; Schutz, Yves Roland; Schwarz, Kilian Eberhard; Schweda, Kai Oliver; Scioli, Gilda; Scomparin, Enrico; Sefcik, Michal; Seger, Janet Elizabeth; Sekiguchi, Yuko; Sekihata, Daiki; Selyuzhenkov, Ilya; Senosi, Kgotlaesele; Senyukov, Serhiy; Serradilla Rodriguez, Eulogio; Sett, Priyanka; Sevcenco, Adrian; Shabanov, Arseniy; Shabetai, Alexandre; Shahoyan, Ruben; Shaikh, Wadut; Shangaraev, Artem; Sharma, Anjali; Sharma, Ankita; Sharma, Meenakshi; Sharma, Natasha; Sheikh, Ashik Ikbal; Shigaki, Kenta; Shimomura, Maya; Shirinkin, Sergey; Shou, Qiye; Shtejer Diaz, Katherin; Sibiryak, Yury; Siddhanta, Sabyasachi; Sielewicz, Krzysztof Marek; Siemiarczuk, Teodor; Silvermyr, David Olle Rickard; Simatovic, Goran; Simonetti, Giuseppe; Singaraju, Rama Narayana; Singh, Ranbir; Singh, Randhir; Singhal, Vikas; Sarkar - Sinha, Tinku; Sitar, Branislav; Sitta, Mario; Skaali, Bernhard; Slupecki, Maciej; Smirnov, Nikolai; Snellings, Raimond; Snellman, Tomas Wilhelm; Song, Jihye; Soramel, Francesca; Sorensen, Soren Pontoppidan; Sozzi, Federica; Sputowska, Iwona Anna; Stachel, Johanna; Stan, Ionel; Stankus, Paul; Stenlund, Evert Anders; Stocco, Diego; Storetvedt, Maksim Melnik; Strmen, Peter; Alarcon Do Passo Suaide, Alexandre; Sugitate, Toru; Suire, Christophe Pierre; Suleymanov, Mais Kazim Oglu; Suljic, Miljenko; Sultanov, Rishat; Sumbera, Michal; Sumowidagdo, Suharyo; Suzuki, Ken; Swain, Sagarika; Szabo, Alexander; Szarka, Imrich; Tabassam, Uzma; Takahashi, Jun; Tambave, Ganesh Jagannath; Tanaka, Naoto; Tarhini, Mohamad; Tariq, Mohammad; Tarzila, Madalina-gabriela; Tauro, Arturo; Tejeda Munoz, Guillermo; Telesca, Adriana; Terrevoli, Cristina; Teyssier, Boris; Thakur, Dhananjaya; Thakur, Sanchari; Thomas, Deepa; Thoresen, Freja; Tieulent, Raphael Noel; Tikhonov, Anatoly; Timmins, Anthony Robert; Toia, Alberica; Topilskaya, Nataliya; Toppi, Marco; Rojas Torres, Solangel; Tripathy, Sushanta; Trogolo, Stefano; Trombetta, Giuseppe; Tropp, Lukas; Trubnikov, Victor; Trzaska, Wladyslaw Henryk; Trzcinski, Tomasz Piotr; Trzeciak, Barbara Antonina; Tsuji, Tomoya; Tumkin, Alexandr; Turrisi, Rosario; Tveter, Trine Spedstad; Ullaland, Kjetil; Umaka, Ejiro Naomi; Uras, Antonio; Usai, Gianluca; Utrobicic, Antonija; Vala, Martin; Van Hoorne, Jacobus Willem; Van Leeuwen, Marco; Vande Vyvre, Pierre; Varga, Dezso; Diozcora Vargas Trevino, Aurora; Vargyas, Marton; Varma, Raghava; Vasileiou, Maria; Vasiliev, Andrey; Vauthier, Astrid; Vazquez Doce, Oton; Vechernin, Vladimir; Veen, Annelies Marianne; Velure, Arild; Vercellin, Ermanno; Vergara Limon, Sergio; Vermunt, Luuk; Vernet, Renaud; Vertesi, Robert; Vickovic, Linda; Viinikainen, Jussi Samuli; Vilakazi, Zabulon; Villalobos Baillie, Orlando; Villatoro Tello, Abraham; Vinogradov, Alexander; Virgili, Tiziano; Vislavicius, Vytautas; Vodopyanov, Alexander; Volkl, Martin Andreas; Voloshin, Kirill; Voloshin, Sergey; Volpe, Giacomo; Von Haller, Barthelemy; Vorobyev, Ivan; Voscek, Dominik; Vranic, Danilo; Vrlakova, Janka; Wagner, Boris; Wang, Hongkai; Wang, Mengliang; Watanabe, Yosuke; Weber, Michael; Weber, Steffen Georg; Wegrzynek, Adam; Weiser, Dennis Franz; Wenzel, Sandro Christian; Wessels, Johannes Peter; Westerhoff, Uwe; Whitehead, Andile Mothegi; Wiechula, Jens; Wikne, Jon; Wilk, Grzegorz Andrzej; Wilkinson, Jeremy John; Willems, Guido Alexander; Williams, Crispin; Willsher, Emily; Windelband, Bernd Stefan; Witt, William Edward; Xu, Ran; Yalcin, Serpil; Yamakawa, Kosei; Yano, Satoshi; Yin, Zhongbao; Yokoyama, Hiroki; Yoo, In-kwon; Yoon, Jin Hee; Yurchenko, Volodymyr; Zaccolo, Valentina; Zaman, Ali; Zampolli, Chiara; Correa Zanoli, Henrique Jose; Zardoshti, Nima; Zarochentsev, Andrey; Zavada, Petr; Zavyalov, Nikolay; Zbroszczyk, Hanna Paulina; Zhalov, Mikhail; Zhang, Xiaoming; Zhang, Yonghong; Zhang, Zuman; Zhao, Chengxin; Zherebchevskii, Vladimir; Zhigareva, Natalia; Zhou, Daicui; Zhou, You; Zhou, Zhuo; Zhu, Hongsheng; Zhu, Jianhui; Zhu, Ya; Zichichi, Antonino; Zimmermann, Markus Bernhard; Zinovjev, Gennady; Zmeskal, Johann; Zou, Shuguang

    2018-01-01

    The production of the $\\rho(770)^{0}$ meson has been measured at mid-rapidity (|y| < 0.5) in pp and centrality differential Pb-Pb collisions at $\\sqrt{s_{NN}}$ = 2.76 TeV with the ALICE detector at the Large Hadron Collider. The particles have been reconstructed in the $\\rho(770)^{0}\\rightarrow \\pi^{+}\\pi^{-}$ decay channel in the transverse momentum ($p_{T}$) range 0.5 − 11 GeV/$c$. A centrality dependent suppression of the ratio of the integrated yields $2\\rho(770)^{0}/(\\pi^{+}+\\pi^{-})$ is observed. The ratio decreases by ~40% from pp to central Pb-Pb collisions. A study of the $p_{T}$-differential $2\\rho(770)^{0}/(\\pi^{+}+\\pi^{-})$ ratio reveals that the suppression occurs at low transverse momenta, $p_{T}$ < 2 GeV/$c$. At higher momentum, particle ratios measured in heavy-ion and pp collisions are consistent. The observed suppression is very similar to that previously measured for the $K^{*}(892)^{0}/K$ ratio and is consistent with EPOS3 predictions that may imply that rescattering in the hadroni...

  5. Degeneration of articular cartilage in osteonecrosis of the femoral head begins at the necrotic region after collapse: a preliminary study using T1 rho MRI

    Energy Technology Data Exchange (ETDEWEB)

    Sonoda, Kazuhiko; Motomura, Goro; Nakashima, Yasuharu [Kyushu University, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Kawanami, Satoshi; Takayama, Yukihisa; Honda, Hiroshi [Kyushu University, Department of Clinical Radiology, Graduate School of Medical Sciences, Higashi-ku, Fukuoka (Japan); Yamamoto, Takuaki [Fukuoka University, Department of Orthopaedic Surgery, Faculty of Medicine, Jonan-ku, Fukuoka (Japan)

    2017-04-15

    The purpose of this study is to evaluate the role of collapse on the degeneration of articular cartilage in patients with osteonecrosis of the femoral head (ONFH). Sixteen hips in 12 patients (four men, eight women; mean age, 34.8 years) with a history of systemic corticosteroid treatment were studied using T1 rho magnetic resonance imaging (MRI). Six hips had collapsed ONFH, five had non-collapsed ONFH, and five had no osteonecrosis (controls). Using oblique coronal images, we divided the articular surface of necrotic femoral heads into a region just above the necrotic bone (necrotic zone) and another above the living bone (living zone). T1 rho value was evaluated for each zone. The mean T1 rho value in the necrotic zone was significantly higher in the collapsed ONFH group (48.4 ± 2.7 ms) than in the non-collapsed ONFH group (41.0 ± 0.9 ms). In the collapsed ONFH group, the mean T1 rho value was significantly higher in the necrotic zone (48.4 ± 2.7 ms) than in the living zone (43.5 ± 2.5 ms). In the non-collapsed ONFH group, there was no significant difference between the mean T1 rho values of the necrotic and living zones. In the collapsed ONFH group, the mean T1 rho value of the necrotic zone and the interval from pain onset to the MRI examination were positively correlated. The current T1 rho MRI study suggested that the degeneration of articular cartilage in ONFH begins at the necrotic region after collapse. (orig.)

  6. Inhibitory effect of rhynchophylline on contraction of cerebral arterioles to endothelin 1: role of rho kinase.

    Science.gov (United States)

    Hao, Hui-Feng; Liu, Li-Mei; Liu, Yu-Ying; Liu, Juan; Yan, Li; Pan, Chun-Shui; Wang, Ming-Xia; Wang, Chuan-She; Fan, Jing-Yu; Gao, Yuan-Sheng; Han, Jing-Yan

    2014-08-08

    Rhynchophylline (Rhy) is a major ingredient of Uncaria rhynchophylla (UR) used to reduce blood pressure and ameliorate brain ailments. This study was to examine the role of Rho kinase (ROCK) in the inhibition of Rhy on contraction of cerebral arterioles caused by endothelin 1 (ET-1). Cerebral arterioles of male Wistar rats were constricted with ET-1 for 10 min followed by perfusion of Rhy for 20 min. Changes in the diameters of the arterioles were recorded. The effects of Rhy on contraction of middle cerebral arteries (MCAs) were determined by a Multi-Myograph. Western blotting and immunofluorescent staining were used to examine the effects of Rhy on RhoA translocation and myosin phosphatase target subunit 1 (MYPT1) phosphorylation. In vivo, Rhy (30-300 µM) relaxed cerebral arterioles constricted with ET-1 dose-dependently. In vitro, Rhy at lower concentrations (1-100 µM) caused relaxation of rat MCAs constricted with KCl and Bay-K8644 (an agonist of L-type voltage-dependent calcium channels (L-VDCCs)). Rhy at higher concentrations (>100 µM) caused relaxation of rat MCAs constricted with ET-1, which was inhibited by Y27632, a ROCK׳s inhibitor. Western blotting of rat aortas showed that Rhy inhibited RhoA translocation and MYPT1 phosphorylation. Immunofluorescent staining of MCAs confirmed that phosphorylation of MYPT1 caused by ET-1 was inhibited by Rhy. These results demonstrate that Rhy is a potent inhibitor of contraction of cerebral arteries caused by ET-1 in vivo and in vitro. The effect of Rhy was in part mediated by inhibiting RhoA-ROCK signaling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. The roles of interleukin-1 and RhoA signaling pathway in rat epilepsy model treated with low-frequency electrical stimulation.

    Science.gov (United States)

    Liu, Ai-Hua; Wu, Ya-Ting; Li, Li-Ping; Wang, Yu-Ping

    2018-03-01

    This study aims to explore the correlation between interleukin-1 (IL-1) and epilepsy in rats when treated with low-frequency electrical stimulation via the RhoA/ROCK signaling pathway. Twenty-four SD rats were elected for this study, among which six rats were assigned as the normal group. And 16 rat models with epilepsy were successfully established and assigned into the model group, the ES group and the ES + IL-8 group, with each group comprising of six rats. The seizure frequency and duration was recorded. Electroencephalogram (EEG) power was detected at α1, α2, β, θ, and δ. The mRNA expressions of IL-1β and IL-1R1 were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR), and the protein expressions of RhoA, ROCK I and ROCK II were detected by western blotting. In comparison with the model group, the seizure frequency duration, the power of δ, θ, α1, α2, and β, the mRNA and protein expressions of IL-1β and IL-1R1, the expressions of RhoA and ROCK I proteins, and the ratio of RhoA protein between membrane and cytosol decreased in the ES group, while the expression of ROCK II increased (all P  0.05). These findings signified that IL-1 might inhibit the efficacy of low-frequency ES for epilepsy via the RhoA/ROCK signaling pathway, which may provide a theoretical basis for clinical treatment of epilepsy. © 2017 Wiley Periodicals, Inc.

  8. Search for exclusive Higgs and $Z$ boson decays to $\\phi\\gamma$ and $\\rho\\gamma$ with the ATLAS detector

    CERN Document Server

    Aaboud, Morad; ATLAS Collaboration; Abbott, Brad; Abdinov, Ovsat; Abeloos, Baptiste; Abidi, Syed Haider; AbouZeid, Ossama; Abraham, Nicola; Abramowicz, Halina; Abreu, Henso; Abreu, Ricardo; Abulaiti, Yiming; Acharya, Bobby Samir; Adachi, Shunsuke; Adamczyk, Leszek; Adelman, Jahred; Adersberger, Michael; Adye, Tim; Affolder, Tony; Afik, Yoav; Agatonovic-Jovin, Tatjana; Agheorghiesei, Catalin; Aguilar-Saavedra, Juan Antonio; Ahlen, Steven; Ahmadov, Faig; Aielli, Giulio; Akatsuka, Shunichi; Akerstedt, Henrik; Åkesson, Torsten Paul Ake; Akilli, Ece; Akimov, Andrei; Alberghi, Gian Luigi; Albert, Justin; Albicocco, Pietro; Alconada Verzini, Maria Josefina; Alderweireldt, Sara; Aleksa, Martin; Aleksandrov, Igor; Alexa, Calin; Alexander, Gideon; Alexopoulos, Theodoros; Alhroob, Muhammad; Ali, Babar; Aliev, Malik; Alimonti, Gianluca; Alison, John; Alkire, Steven Patrick; Allbrooke, Benedict; Allen, Benjamin William; Allport, Phillip; Aloisio, Alberto; Alonso, Alejandro; Alonso, Francisco; Alpigiani, Cristiano; Alshehri, Azzah Aziz; Alstaty, Mahmoud; Alvarez Gonzalez, Barbara; Άlvarez Piqueras, Damián; Alviggi, Mariagrazia; Amadio, Brian Thomas; Amaral Coutinho, Yara; Amelung, Christoph; Amidei, Dante; Amor Dos Santos, Susana Patricia; Amoroso, Simone; Amundsen, Glenn; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, John Kenneth; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Angelidakis, Stylianos; Angelozzi, Ivan; Angerami, Aaron; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antel, Claire; Antonelli, Mario; Antonov, Alexey; Antrim, Daniel Joseph; Anulli, Fabio; Aoki, Masato; Aperio Bella, Ludovica; Arabidze, Giorgi; Arai, Yasuo; Araque, Juan Pedro; Araujo Ferraz, Victor; Arce, Ayana; Ardell, Rose Elisabeth; Arduh, Francisco Anuar; Arguin, Jean-Francois; Argyropoulos, Spyridon; Arik, Metin; Armbruster, Aaron James; Armitage, Lewis James; Arnaez, Olivier; Arnold, Hannah; Arratia, Miguel; Arslan, Ozan; Artamonov, Andrei; Artoni, Giacomo; Artz, Sebastian; Asai, Shoji; Asbah, Nedaa; Ashkenazi, Adi; Asquith, Lily; Assamagan, Ketevi; Astalos, Robert; Atkinson, Markus; Atlay, Naim Bora; Augsten, Kamil; Avolio, Giuseppe; Axen, Bradley; Ayoub, Mohamad Kassem; Azuelos, Georges; Baas, Alessandra; Baca, Matthew John; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Bagnaia, Paolo; Bahmani, Marzieh; Bahrasemani, Sina; Baines, John; Bajic, Milena; Baker, Oliver Keith; Bakker, Pepijn Johannes; Baldin, Evgenii; Balek, Petr; Balli, Fabrice; Balunas, William Keaton; Banas, Elzbieta; Bandyopadhyay, Anjishnu; Banerjee, Swagato; Bannoura, Arwa A E; Barak, Liron; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Barillari, Teresa; Barisits, Martin-Stefan; Barkeloo, Jason Tyler Colt; Barklow, Timothy; Barlow, Nick; Barnes, Sarah Louise; Barnett, Bruce; Barnett, Michael; Barnovska-Blenessy, Zuzana; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barranco Navarro, Laura; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Bartoldus, Rainer; Barton, Adam Edward; Bartos, Pavol; Basalaev, Artem; Bassalat, Ahmed; Bates, Richard; Batista, Santiago Juan; Batley, Richard; Battaglia, Marco; Bauce, Matteo; Bauer, Florian; Bawa, Harinder Singh; Beacham, James; Beattie, Michael David; Beau, Tristan; Beauchemin, Pierre-Hugues; Bechtle, Philip; Beck, Hans~Peter; Beck, Helge Christoph; Becker, Kathrin; Becker, Maurice; Becot, Cyril; Beddall, Andrew; Beddall, Ayda; Bednyakov, Vadim; Bedognetti, Matteo; Bee, Christopher; Beermann, Thomas; Begalli, Marcia; Begel, Michael; Behr, Janna Katharina; Bell, Andrew Stuart; Bella, Gideon; Bellagamba, Lorenzo; Bellerive, Alain; Bellomo, Massimiliano; Belotskiy, Konstantin; Beltramello, Olga; Belyaev, Nikita; Benary, Odette; Benchekroun, Driss; Bender, Michael; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez, Jose; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Bentvelsen, Stan; Beresford, Lydia; Beretta, Matteo; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Bergsten, Laura Jean; Beringer, Jürg; Berlendis, Simon; Bernard, Nathan Rogers; Bernardi, Gregorio; Bernius, Catrin; Bernlochner, Florian Urs; Berry, Tracey; Berta, Peter; Bertella, Claudia; Bertoli, Gabriele; Bertram, Iain Alexander; Bertsche, Carolyn; Besjes, Geert-Jan; Bessidskaia Bylund, Olga; Bessner, Martin Florian; Besson, Nathalie; Bethani, Agni; Bethke, Siegfried; Betti, Alessandra; Bevan, Adrian John; Beyer, Julien-christopher; Bianchi, Riccardo-Maria; Biebel, Otmar; Biedermann, Dustin; Bielski, Rafal; Bierwagen, Katharina; Biesuz, Nicolo Vladi; Biglietti, Michela; Billoud, Thomas Remy Victor; Bilokon, Halina; Bindi, Marcello; Bingul, Ahmet; Bini, Cesare; Biondi, Silvia; Bisanz, Tobias; Bittrich, Carsten; Bjergaard, David Martin; Black, James; Black, Kevin; Blair, Robert; Blazek, Tomas; Bloch, Ingo; Blocker, Craig; Blue, Andrew; Blumenschein, Ulrike; Blunier, Sylvain; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Bock, Christopher; Boehler, Michael; Boerner, Daniela; Bogavac, Danijela; Bogdanchikov, Alexander; Bohm, Christian; Boisvert, Veronique; Bokan, Petar; Bold, Tomasz; Boldyrev, Alexey; Bolz, Arthur Eugen; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Borisov, Anatoly; Borissov, Guennadi; Bortfeldt, Jonathan; Bortoletto, Daniela; Bortolotto, Valerio; Boscherini, Davide; Bosman, Martine; Bossio Sola, Jonathan David; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Boutle, Sarah Kate; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozson, Adam James; Bracinik, Juraj; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Braren, Frued; Bratzler, Uwe; Brau, Benjamin; Brau, James; Breaden Madden, William Dmitri; Brendlinger, Kurt; Brennan, Amelia Jean; Brenner, Lydia; Brenner, Richard; Bressler, Shikma; Briglin, Daniel Lawrence; Bristow, Timothy Michael; Britton, Dave; Britzger, Daniel; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brosamer, Jacquelyn; Brost, Elizabeth; Broughton, James; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruni, Alessia; Bruni, Graziano; Bruni, Lucrezia Stella; Bruno, Salvatore; Brunt, Benjamin; Bruschi, Marco; Bruscino, Nello; Bryant, Patrick; Bryngemark, Lene; Buanes, Trygve; Buat, Quentin; Buchholz, Peter; Buckley, Andrew; Budagov, Ioulian; Buehrer, Felix; Bugge, Magnar Kopangen; Bulekov, Oleg; Bullock, Daniel; Burch, Tyler James; Burdin, Sergey; Burgard, Carsten Daniel; Burger, Angela Maria; Burghgrave, Blake; Burka, Klaudia; Burke, Stephen; Burmeister, Ingo; Burr, Jonathan Thomas Peter; Büscher, Daniel; Büscher, Volker; Bussey, Peter; Butler, John; Buttar, Craig; Butterworth, Jonathan; Butti, Pierfrancesco; Buttinger, William; Buzatu, Adrian; Buzykaev, Aleksey; C-Q, Changqiao; Cabrera Urbán, Susana; Caforio, Davide; Cai, Huacheng; Cairo, Valentina; Cakir, Orhan; Calace, Noemi; Calafiura, Paolo; Calandri, Alessandro; Calderini, Giovanni; Calfayan, Philippe; Callea, Giuseppe; Caloba, Luiz; Calvente Lopez, Sergio; Calvet, David; Calvet, Samuel; Calvet, Thomas Philippe; Camacho Toro, Reina; Camarda, Stefano; Camarri, Paolo; Cameron, David; Caminal Armadans, Roger; Camincher, Clement; Campana, Simone; Campanelli, Mario; Camplani, Alessandra; Campoverde, Angel; Canale, Vincenzo; Cano Bret, Marc; Cantero, Josu; Cao, Tingting; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capua, Marcella; Carbone, Ryne Michael; Cardarelli, Roberto; Cardillo, Fabio; Carli, Ina; Carli, Tancredi; Carlino, Gianpaolo; Carlson, Benjamin Taylor; Carminati, Leonardo; Carney, Rebecca; Caron, Sascha; Carquin, Edson; Carrá, Sonia; Carrillo-Montoya, German D; Casadei, Diego; Casado, Maria Pilar; Casha, Albert Francis; Casolino, Mirkoantonio; Casper, David William; Castelijn, Remco; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Caudron, Julien; Cavaliere, Viviana; Cavallaro, Emanuele; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Celebi, Emre; Ceradini, Filippo; Cerda Alberich, Leonor; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cervelli, Alberto; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chan, Stephen Kam-wah; Chan, Wing Sheung; Chan, Yat Long; Chang, Philip; Chapman, John Derek; Charlton, David; Chau, Chav Chhiv; Chavez Barajas, Carlos Alberto; Che, Siinn; Cheatham, Susan; Chegwidden, Andrew; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Cheng; Chen, Chunhui; Chen, Hucheng; Chen, Jing; Chen, Shenjian; Chen, Shion; Chen, Xin; Chen, Ye; Cheng, Hok Chuen; Cheng, Huajie; Cheplakov, Alexander; Cheremushkina, Evgeniya; Cherkaoui El Moursli, Rajaa; Cheu, Elliott; Cheung, Kingman; Chevalier, Laurent; Chiarella, Vitaliano; Chiarelli, Giorgio; Chiodini, Gabriele; Chisholm, Andrew; Chitan, Adrian; Chiu, Yu Him Justin; Chizhov, Mihail; Choi, Kyungeon; Chomont, Arthur Rene; Chouridou, Sofia; Chow, Yun Sang; Christodoulou, Valentinos; Chu, Ming Chung; Chudoba, Jiri; Chuinard, Annabelle Julia; Chwastowski, Janusz; Chytka, Ladislav; Ciftci, Abbas Kenan; Cinca, Diane; Cindro, Vladimir; Cioară, Irina Antonela; Ciocio, Alessandra; Cirotto, Francesco; Citron, Zvi Hirsh; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Brian Lee; Clark, Michael; Clark, Philip James; Clarke, Robert; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Colasurdo, Luca; Cole, Brian; Colijn, Auke-Pieter; Collot, Johann; Colombo, Tommaso; Conde Muiño, Patricia; Coniavitis, Elias; Connell, Simon Henry; Connelly, Ian; Constantinescu, Serban; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper-Sarkar, Amanda; Cormier, Felix; Cormier, Kyle James Read; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Cottin, Giovanna; Cowan, Glen; Cox, Brian; Cranmer, Kyle; Crawley, Samuel Joseph; Creager, Rachael; Cree, Graham; Crépé-Renaudin, Sabine; Crescioli, Francesco; Cribbs, Wayne Allen; Cristinziani, Markus; Croft, Vince; Crosetti, Giovanni; Cueto, Ana; Cuhadar Donszelmann, Tulay; Cukierman, Aviv Ruben; Cummings, Jane; Curatolo, Maria; Cúth, Jakub; Czekierda, Sabina; Czodrowski, Patrick; D'amen, Gabriele; D'Auria, Saverio; D'eramo, Louis; D'Onofrio, Monica; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dado, Tomas; Dai, Tiesheng; Dale, Orjan; Dallaire, Frederick; Dallapiccola, Carlo; Dam, Mogens; Dandoy, Jeffrey; Daneri, Maria Florencia; Dang, Nguyen Phuong; Daniells, Andrew Christopher; Dann, Nicholas Stuart; Danninger, Matthias; Dano Hoffmann, Maria; Dao, Valerio; Darbo, Giovanni; Darmora, Smita; Dassoulas, James; Dattagupta, Aparajita; Daubney, Thomas; Davey, Will; David, Claire; Davidek, Tomas; Davis, Douglas; Davison, Peter; Dawe, Edmund; Dawson, Ian; De, Kaushik; de Asmundis, Riccardo; De Benedetti, Abraham; De Castro, Stefano; De Cecco, Sandro; De Groot, Nicolo; de Jong, Paul; De la Torre, Hector; De Lorenzi, Francesco; De Maria, Antonio; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vasconcelos Corga, Kevin; De Vivie De Regie, Jean-Baptiste; Debbe, Ramiro; Debenedetti, Chiara; Dedovich, Dmitri; Dehghanian, Nooshin; Deigaard, Ingrid; Del Gaudio, Michela; Del Peso, Jose; Delgove, David; Deliot, Frederic; Delitzsch, Chris Malena; Dell'Acqua, Andrea; Dell'Asta, Lidia; Dell'Orso, Mauro; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delporte, Charles; Delsart, Pierre-Antoine; DeMarco, David; Demers, Sarah; Demichev, Mikhail; Demilly, Aurelien; Denisov, Sergey; Denysiuk, Denys; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Deterre, Cecile; Dette, Karola; Devesa, Maria Roberta; Deviveiros, Pier-Olivier; Dewhurst, Alastair; Dhaliwal, Saminder; Di Bello, Francesco Armando; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Clemente, William Kennedy; Di Donato, Camilla; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Micco, Biagio; Di Nardo, Roberto; Di Petrillo, Karri Folan; Di Simone, Andrea; Di Sipio, Riccardo; Di Valentino, David; Diaconu, Cristinel; Diamond, Miriam; Dias, Flavia; Diaz, Marco Aurelio; Dickinson, Jennet; Diehl, Edward; Dietrich, Janet; Díez Cornell, Sergio; Dimitrievska, Aleksandra; Dingfelder, Jochen; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Djuvsland, Julia Isabell; Barros do Vale, Maria Aline; Dobos, Daniel; Dobre, Monica; Dodsworth, David; Doglioni, Caterina; Dolejsi, Jiri; Dolezal, Zdenek; Donadelli, Marisilvia; Donati, Simone; Dondero, Paolo; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dova, Maria-Teresa; Doyle, Tony; Drechsler, Eric; Dris, Manolis; Du, Yanyan; Duarte-Campderros, Jorge; Dubinin, Filipp; Dubreuil, Arnaud; Duchovni, Ehud; Duckeck, Guenter; Ducourthial, Audrey; Ducu, Otilia Anamaria; Duda, Dominik; Dudarev, Alexey; Dudder, Andreas Christian; Duffield, Emily Marie; Duflot, Laurent; Dührssen, Michael; Dulsen, Carsten; Dumancic, Mirta; Dumitriu, Ana Elena; Duncan, Anna Kathryn; Dunford, Monica; Duperrin, Arnaud; Duran Yildiz, Hatice; Düren, Michael; Durglishvili, Archil; Duschinger, Dirk; Dutta, Baishali; Duvnjak, Damir; Dyndal, Mateusz; Dziedzic, Bartosz Sebastian; Eckardt, Christoph; Ecker, Katharina Maria; Edgar, Ryan Christopher; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Ekelof, Tord; El Kacimi, Mohamed; El Kosseifi, Rima; Ellajosyula, Venugopal; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Elliot, Alison; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Enari, Yuji; Ennis, Joseph Stanford; Epland, Matthew Berg; Erdmann, Johannes; Ereditato, Antonio; Ernst, Michael; Errede, Steven; Escalier, Marc; Escobar, Carlos; Esposito, Bellisario; Estrada Pastor, Oscar; Etienvre, Anne-Isabelle; Etzion, Erez; Evans, Hal; Ezhilov, Alexey; Ezzi, Mohammed; Fabbri, Federica; Fabbri, Laura; Fabiani, Veronica; Facini, Gabriel; Fakhrutdinov, Rinat; Falciano, Speranza; Falla, Rebecca Jane; Faltova, Jana; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farina, Christian; Farina, Edoardo Maria; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassi, Farida; Fassnacht, Patrick; Fassouliotis, Dimitrios; Faucci Giannelli, Michele; Favareto, Andrea; Fawcett, William James; Fayard, Louis; Fedin, Oleg; Fedorko, Wojciech; Feigl, Simon; Feligioni, Lorenzo; Feng, Cunfeng; Feng, Eric; Fenton, Michael James; Fenyuk, Alexander; Feremenga, Last; Fernandez Martinez, Patricia; Ferrando, James; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Fiedler, Frank; Filipčič, Andrej; Filipuzzi, Marco; Filthaut, Frank; Fincke-Keeler, Margret; Finelli, Kevin Daniel; Fiolhais, Miguel; Fiorini, Luca; Fischer, Adam; Fischer, Cora; Fischer, Julia; Fisher, Wade Cameron; Flaschel, Nils; Fleck, Ivor; Fleischmann, Philipp; Fletcher, Rob Roy MacGregor; Flick, Tobias; Flierl, Bernhard Matthias; Flores Castillo, Luis; Flowerdew, Michael; Forcolin, Giulio Tiziano; Formica, Andrea; Förster, Fabian Alexander; Forti, Alessandra; Foster, Andrew Geoffrey; Fournier, Daniel; Fox, Harald; Fracchia, Silvia; Francavilla, Paolo; Franchini, Matteo; Franchino, Silvia; Francis, David; Franconi, Laura; Franklin, Melissa; Frate, Meghan; Fraternali, Marco; Freeborn, David; Fressard-Batraneanu, Silvia; Freund, Benjamin; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fusayasu, Takahiro; Fuster, Juan; Gabizon, Ofir; Gabrielli, Alessandro; Gabrielli, Andrea; Gach, Grzegorz; Gadatsch, Stefan; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Louis Guillaume; Galea, Cristina; Galhardo, Bruno; Gallas, Elizabeth; Gallop, Bruce; Gallus, Petr; Galster, Gorm Aske Gram Krohn; Gan, KK; Ganguly, Sanmay; Gao, Yanyan; Gao, Yongsheng; Garay Walls, Francisca; García, Carmen; García Navarro, José Enrique; García Pascual, Juan Antonio; Garcia-Sciveres, Maurice; Gardner, Robert; Garelli, Nicoletta; Garonne, Vincent; Gascon Bravo, Alberto; Gasnikova, Ksenia; Gatti, Claudio; Gaudiello, Andrea; Gaudio, Gabriella; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Gee, Norman; Geisen, Jannik; Geisen, Marc; Geisler, Manuel Patrice; Gellerstedt, Karl; Gemme, Claudia; Genest, Marie-Hélène; Geng, Cong; Gentile, Simonetta; Gentsos, Christos; George, Simon; Gerbaudo, Davide; Geß{}ner, Gregor; Ghasemi, Sara; Ghneimat, Mazuza; Giacobbe, Benedetto; Giagu, Stefano; Giangiacomi, Nico; Giannetti, Paola; Gibson, Stephen; Gignac, Matthew; Gilchriese, Murdock; Gillberg, Dag; Gilles, Geoffrey; Gingrich, Douglas; Giordani, MarioPaolo; Giorgi, Filippo Maria; Giraud, Pierre-Francois; Giromini, Paolo; Giugliarelli, Gilberto; Giugni, Danilo; Giuli, Francesco; Giuliani, Claudia; Giulini, Maddalena; Gjelsten, Børge Kile; Gkaitatzis, Stamatios; Gkialas, Ioannis; Gkougkousis, Evangelos Leonidas; Gkountoumis, Panagiotis; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glaysher, Paul; Glazov, Alexandre; Goblirsch-Kolb, Maximilian; Godlewski, Jan; Goldfarb, Steven; Golling, Tobias; Golubkov, Dmitry; Gomes, Agostinho; Gonçalo, Ricardo; Goncalves Gama, Rafael; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Giulia; Gonella, Laura; Gongadze, Alexi; Gonski, Julia; González de la Hoz, Santiago; Gonzalez-Sevilla, Sergio; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Goshaw, Alfred; Gössling, Claus; Gostkin, Mikhail Ivanovitch; Gottardo, Carlo Alberto; Goudet, Christophe Raymond; Goujdami, Driss; Goussiou, Anna; Govender, Nicolin; Gozani, Eitan; Grabowska-Bold, Iwona; Gradin, Per Olov Joakim; Gramling, Johanna; Gramstad, Eirik; Grancagnolo, Sergio; Gratchev, Vadim; Gravila, Paul Mircea; Gray, Chloe; Gray, Heather; Greenwood, Zeno Dixon; Grefe, Christian; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Grevtsov, Kirill; Griffiths, Justin; Grillo, Alexander; Grimm, Kathryn; Grinstein, Sebastian; Gris, Philippe Luc Yves; Grivaz, Jean-Francois; Groh, Sabrina; Gross, Eilam; Grosse-Knetter, Joern; Grossi, Giulio Cornelio; Grout, Zara Jane; Grummer, Aidan; Guan, Liang; Guan, Wen; Guenther, Jaroslav; Guescini, Francesco; Guest, Daniel; Gueta, Orel; Gui, Bin; Guido, Elisa; Guillemin, Thibault; Guindon, Stefan; Gul, Umar; Gumpert, Christian; Guo, Jun; Guo, Wen; Guo, Yicheng; Gupta, Ruchi; Gurbuz, Saime; Gustavino, Giuliano; Gutelman, Benjamin Jacque; Gutierrez, Phillip; Gutierrez Ortiz, Nicolas Gilberto; Gutschow, Christian; Guyot, Claude; Guzik, Marcin Pawel; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haber, Carl; Hadavand, Haleh Khani; Haddad, Nacim; Hadef, Asma; Hageböck, Stephan; Hagihara, Mutsuto; Hakobyan, Hrachya; Haleem, Mahsana; Haley, Joseph; Halladjian, Garabed; Hallewell, Gregory David; Hamacher, Klaus; Hamal, Petr; Hamano, Kenji; Hamilton, Andrew; Hamity, Guillermo Nicolas; Hamnett, Phillip George; Han, Liang; Han, Shuo; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Handl, David Michael; Haney, Bijan; Hanke, Paul; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Maike Christina; Hansen, Peter Henrik; Hara, Kazuhiko; Hard, Andrew; Harenberg, Torsten; Hariri, Faten; Harkusha, Siarhei; Harrison, Paul Fraser; Hartmann, Nikolai Marcel; Hasegawa, Yoji; Hasib, Ahmed; Hassani, Samira; Haug, Sigve; Hauser, Reiner; Hauswald, Lorenz; Havener, Laura Brittany; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hayakawa, Daiki; Hayden, Daniel; Hays, Chris; Hays, Jonathan Michael; Hayward, Helen; Haywood, Stephen; Head, Simon; Heck, Tobias; Hedberg, Vincent; Heelan, Louise; Heer, Sebastian; Heidegger, Kim Katrin; Heim, Sarah; Heim, Timon; Heinemann, Beate; Heinrich, Jochen Jens; Heinrich, Lukas; Heinz, Christian; Hejbal, Jiri; Helary, Louis; Held, Alexander; Hellman, Sten; Helsens, Clement; Henderson, Robert; Heng, Yang; Henkelmann, Steffen; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Herbert, Geoffrey Henry; Herde, Hannah; Herget, Verena; Hernández Jiménez, Yesenia; Herr, Holger; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Herwig, Theodor Christian; Hesketh, Gavin Grant; Hessey, Nigel; Hetherly, Jeffrey Wayne; Higashino, Satoshi; Higón-Rodriguez, Emilio; Hildebrand, Kevin; Hill, Ewan; Hill, John; Hiller, Karl Heinz; Hillier, Stephen; Hils, Maximilian; Hinchliffe, Ian; Hirose, Minoru; Hirschbuehl, Dominic; Hiti, Bojan; Hladik, Ondrej; Hlaluku, Dingane Reward; Hoad, Xanthe; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoenig, Friedrich; Hohn, David; Holmes, Tova Ray; Holzbock, Michael; Homann, Michael; Honda, Shunsuke; Honda, Takuya; Hong, Tae Min; Hooberman, Benjamin Henry; Hopkins, Walter; Horii, Yasuyuki; Horton, Arthur James; Hostachy, Jean-Yves; Hostiuc, Alexandru; Hou, Suen; Hoummada, Abdeslam; Howarth, James; Hoya, Joaquin; Hrabovsky, Miroslav; Hrdinka, Julia; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hrynevich, Aliaksei; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hu, Qipeng; Hu, Shuyang; Huang, Yanping; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huffman, Todd Brian; Hughes, Emlyn; Huhtinen, Mika; Hunter, Robert Francis Holub; Huo, Peng; Huseynov, Nazim; Huston, Joey; Huth, John; Hyneman, Rachel; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idrissi, Zineb; Iengo, Paolo; Igonkina, Olga; Iizawa, Tomoya; Ikegami, Yoichi; Ikeno, Masahiro; Ilchenko, Yuriy; Iliadis, Dimitrios; Ilic, Nikolina; Iltzsche, Franziska; Introzzi, Gianluca; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Isacson, Max Fredrik; Ishijima, Naoki; Ishino, Masaya; Ishitsuka, Masaki; Issever, Cigdem; Istin, Serhat; Ito, Fumiaki; Iturbe Ponce, Julia Mariana; Iuppa, Roberto; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jabbar, Samina; Jackson, Paul; Jacobs, Ruth Magdalena; Jain, Vivek; Jakobi, Katharina Bianca; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jamin, David Olivier; Jana, Dilip; Jansky, Roland; Janssen, Jens; Janus, Michel; Janus, Piotr Andrzej; Jarlskog, Göran; Javadov, Namig; Javůrek, Tomáš; Javurkova, Martina; Jeanneau, Fabien; Jeanty, Laura; Jejelava, Juansher; Jelinskas, Adomas; Jenni, Peter; Jeske, Carl; Jézéquel, Stéphane; Ji, Haoshuang; Jia, Jiangyong; Jiang, Hai; Jiang, Yi; Jiang, Zihao; Jiggins, Stephen; Jimenez Pena, Javier; Jin, Shan; Jinaru, Adam; Jinnouchi, Osamu; Jivan, Harshna; Johansson, Per; Johns, Kenneth; Johnson, Christian; Johnson, William Joseph; Jon-And, Kerstin; Jones, Roger; Jones, Samuel David; Jones, Sarah; Jones, Tim; Jongmanns, Jan; Jorge, Pedro; Jovicevic, Jelena; Ju, Xiangyang; Juste Rozas, Aurelio; Köhler, Markus Konrad; Kaczmarska, Anna; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kahn, Sebastien Jonathan; Kaji, Toshiaki; Kajomovitz, Enrique; Kalderon, Charles William; Kaluza, Adam; Kama, Sami; Kamenshchikov, Andrey; Kanaya, Naoko; Kanjir, Luka; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kaplan, Laser Seymour; Kar, Deepak; Karakostas, Konstantinos; Karastathis, Nikolaos; Kareem, Mohammad Jawad; 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Klein, Matthew Henry; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klingl, Tobias; Klioutchnikova, Tatiana; Klitzner, Felix Fidelio; Kluge, Eike-Erik; Kluit, Peter; Kluth, Stefan; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Kobayashi, Aine; Kobayashi, Dai; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Koffas, Thomas; Koffeman, Els; Köhler, Nicolas Maximilian; Koi, Tatsumi; Kolb, Mathis; Koletsou, Iro; Kondo, Takahiko; Kondrashova, Nataliia; Köneke, Karsten; König, Adriaan; Kono, Takanori; Konoplich, Rostislav; Konstantinidis, Nikolaos; Konya, Balazs; Kopeliansky, Revital; Koperny, Stefan; Kopp, Anna Katharina; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Kortner, Oliver; Kortner, Sandra; Kosek, Tomas; Kostyukhin, Vadim; Kotwal, Ashutosh; Koulouris, Aimilianos; Kourkoumeli-Charalampidi, Athina; Kourkoumelis, Christine; Kourlitis, Evangelos; Kouskoura, Vasiliki; Kowalewska, Anna Bozena; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozakai, Chihiro; Kozanecki, Witold; Kozhin, Anatoly; Kramarenko, Viktor; Kramberger, Gregor; Krasnopevtsev, Dimitrii; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Krauss, Dominik; Kremer, Jakub Andrzej; Kretzschmar, Jan; Kreutzfeldt, Kristof; Krieger, Peter; Krizka, Karol; Kroeninger, Kevin; Kroha, Hubert; Kroll, Jiri; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Krumnack, Nils; Kruse, Mark; Kubota, Takashi; Kucuk, Hilal; Kuday, Sinan; Kuechler, Jan Thomas; Kuehn, Susanne; Kugel, Andreas; Kuger, Fabian; Kuhl, Thorsten; Kukhtin, Victor; Kukla, Romain; Kulchitsky, Yuri; Kuleshov, Sergey; Kulinich, Yakov Petrovich; Kuna, Marine; Kunigo, Takuto; Kupco, Alexander; Kupfer, Tobias; Kuprash, Oleg; Kurashige, Hisaya; Kurchaninov, Leonid; Kurochkin, Yurii; Kurth, Matthew Glenn; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwan, Tony; Kyriazopoulos, Dimitrios; La Rosa, Alessandro; La Rosa Navarro, Jose Luis; La Rotonda, Laura; La Ruffa, Francesco; Lacasta, Carlos; Lacava, Francesco; Lacey, James; Lack, David Philip John; Lacker, Heiko; Lacour, Didier; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lai, Stanley; Lammers, Sabine; Lampl, Walter; Lançon, Eric; Landgraf, Ulrich; Landon, Murrough; Lanfermann, Marie Christine; Lang, Valerie Susanne; Lange, J örn Christian; Langenberg, Robert Johannes; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Lanza, Agostino; Lapertosa, Alessandro; Laplace, Sandrine; Laporte, Jean-Francois; Lari, Tommaso; Lasagni Manghi, Federico; Lassnig, Mario; Lau, Tak Shun; Laurelli, Paolo; Lavrijsen, Wim; Law, Alexander; Laycock, Paul; Lazovich, Tomo; Lazzaroni, Massimo; Le, Brian; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Quilleuc, Eloi; LeBlanc, Matthew Edgar; LeCompte, Thomas; Ledroit-Guillon, Fabienne; Lee, Claire Alexandra; Lee, Graham Richard; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Benoit; Lefebvre, Guillaume; Lefebvre, Michel; Legger, Federica; Leggett, Charles; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leight, William Axel; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Leney, Katharine; Lenz, Tatjana; Lenzi, Bruno; Leone, Robert; Leone, Sandra; Leonidopoulos, Christos; Lerner, Giuseppe; Leroy, Claude; Les, Robert; Lesage, Arthur; Lester, Christopher; Levchenko, Mikhail; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Levy, Mark; Lewis, Dave; Li, Bing; Li, Haifeng; Li, Liang; Li, Qi; Li, Quanyin; Li, Shu; Li, Xingguo; Li, Yichen; Liang, Zhijun; Liberti, Barbara; Liblong, Aaron; Lie, Ki; Liebal, Jessica; Liebig, Wolfgang; Limosani, Antonio; Lin, Chiao-ying; Lin, Kuan-yu; Lin, Simon; Lin, Tai-Hua; Linck, Rebecca Anne; Lindquist, Brian Edward; Lionti, Anthony Eric; Lipeles, Elliot; Lipniacka, Anna; Lisovyi, Mykhailo; Liss, Tony; Lister, Alison; Litke, Alan; Liu, Bo; Liu, Hao; Liu, Hongbin; Liu, Jesse; Liu, Jian; Liu, Jianbei; Liu, Kun; Liu, Lulu; Liu, Minghui; Liu, Yanlin; Liu, Yanwen; Livan, Michele; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lo, Cheuk Yee; Lo Sterzo, Francesco; Lobodzinska, Ewelina Maria; Loch, Peter; Loebinger, Fred; Loesle, Alena; Loew, Kevin Michael; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Long, Brian Alexander; Long, Jonathan David; Long, Robin Eamonn; Longo, Luigi; Looper, Kristina Anne; Lopez, Jorge; Lopez Paz, Ivan; Lopez Solis, Alvaro; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Lösel, Philipp Jonathan; Lou, XinChou; Lounis, Abdenour; Love, Jeremy; Love, Peter; Lu, Haonan; Lu, Nan; Lu, Yun-Ju; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Luedtke, Christian; Luehring, Frederick; Lukas, Wolfgang; Luminari, Lamberto; Lundberg, Olof; Lund-Jensen, Bengt; Lutz, Margaret Susan; Luzi, Pierre Marc; Lynn, David; Lysak, Roman; Lytken, Else; Lyu, Feng; Lyubushkin, Vladimir; Ma, Hong; Ma, Lian Liang; Ma, Yanhui; Maccarrone, Giovanni; Macchiolo, Anna; Macdonald, Calum Michael; Maček, Boštjan; Machado Miguens, Joana; 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Martin, Christopher Blake; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martinez, Mario; Martinez Outschoorn, Verena; Martin-Haugh, Stewart; Martoiu, Victor Sorin; Martyniuk, Alex; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Mason, Lara Hannan; Massa, Lorenzo; Mastrandrea, Paolo; Mastroberardino, Anna; Masubuchi, Tatsuya; Mättig, Peter; Maurer, Julien; Maxfield, Stephen; Maximov, Dmitriy; Mazini, Rachid; Maznas, Ioannis; Mazza, Simone Michele; Mc Fadden, Neil Christopher; Mc Goldrick, Garrin; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Thomas; McClymont, Laurie; McDonald, Emily; Mcfayden, Josh; Mchedlidze, Gvantsa; McMahon, Steve; McNamara, Peter Charles; McNicol, Christopher John; McPherson, Robert; Meehan, Samuel; Megy, Theo Jean; Mehlhase, Sascha; Mehta, Andrew; Meideck, Thomas; Meier, Karlheinz; Meirose, Bernhard; Melini, Davide; Mellado Garcia, Bruce Rafael; Mellenthin, Johannes Donatus; Melo, Matej; Meloni, Federico; Melzer, Alexander; Menary, Stephen Burns; Meng, Lingxin; Meng, Xiangting; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mergelmeyer, Sebastian; Merlassino, Claudia; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer Zu Theenhausen, Hanno; Miano, Fabrizio; Middleton, Robin; Miglioranzi, Silvia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Milesi, Marco; Milic, Adriana; Millar, Declan Andrew; Miller, David; Mills, Corrinne; Milov, Alexander; Milstead, David; Minaenko, Andrey; Minami, Yuto; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Minegishi, Yuji; Ming, Yao; Mir, Lluisa-Maria; Mirto, Alessandro; Mistry, Khilesh; Mitani, Takashi; Mitrevski, Jovan; Mitsou, Vasiliki A; Miucci, Antonio; Miyagawa, Paul; Mizukami, Atsushi; Mjörnmark, Jan-Ulf; Mkrtchyan, Tigran; Mlynarikova, Michaela; Moa, Torbjoern; Mochizuki, Kazuya; Mogg, Philipp; Mohapatra, Soumya; Molander, Simon; Moles-Valls, Regina; Mondragon, Matthew Craig; Mönig, Klaus; Monk, James; Monnier, Emmanuel; Montalbano, Alyssa; Montejo Berlingen, Javier; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Morange, Nicolas; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Stefanie; Mori, Daniel; Mori, Tatsuya; Morii, Masahiro; Morinaga, Masahiro; Morisbak, Vanja; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moschovakos, Paris; Mosidze, Maia; Moss, Harry James; Moss, Josh; Motohashi, Kazuki; Mount, Richard; Mountricha, Eleni; Moyse, Edward; Muanza, Steve; Mueller, Felix; Mueller, James; Mueller, Ralph Soeren Peter; Muenstermann, Daniel; Mullen, Paul; Mullier, Geoffrey; Munoz Sanchez, Francisca Javiela; Murray, Bill; Musheghyan, Haykuhi; Muškinja, Miha; Myagkov, Alexey; Myska, Miroslav; Nachman, Benjamin Philip; Nackenhorst, Olaf; Nagai, Koichi; Nagai, Ryo; Nagano, Kunihiro; Nagasaka, Yasushi; Nagata, Kazuki; Nagel, Martin; Nagy, Elemer; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Naranjo Garcia, Roger Felipe; Narayan, Rohin; Narrias Villar, Daniel Isaac; Naryshkin, Iouri; Naumann, Thomas; Navarro, Gabriela; Nayyar, Ruchika; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negrini, Matteo; Nektarijevic, Snezana; Nellist, Clara; Nelson, Andrew; Nelson, Michael Edward; Nemecek, Stanislav; Nemethy, Peter; Nessi, Marzio; Neubauer, Mark; Neumann, Manuel; Newman, Paul; Ng, Tsz Yu; Ng, Sam Yanwing; Nguyen Manh, Tuan; Nickerson, Richard; Nicolaidou, Rosy; Nielsen, Jason; Nikiforou, Nikiforos; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolopoulos, Konstantinos; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nishu, Nishu; Nisius, Richard; Nitsche, Isabel; Nitta, Tatsumi; Nobe, Takuya; Noguchi, Yohei; Nomachi, Masaharu; Nomidis, Ioannis; Nomura, Marcelo Ayumu; Nooney, Tamsin; Nordberg, Markus; Norjoharuddeen, Nurfikri; Novgorodova, Olga; Nozaki, Mitsuaki; Nozka, Libor; Ntekas, Konstantinos; Nurse, Emily; Nuti, Francesco; O'connor, Kelsey; O'Neil, Dugan; O'Rourke, Abigail Alexandra; O'Shea, Val; Oakham, Gerald; Oberlack, Horst; Obermann, Theresa; Ocariz, Jose; Ochi, Atsuhiko; Ochoa, Ines; Ochoa-Ricoux, Juan Pedro; Oda, Susumu; Odaka, Shigeru; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohman, Henrik; Oide, Hideyuki; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Oleiro Seabra, Luis Filipe; Olivares Pino, Sebastian Andres; Oliveira Damazio, Denis; Olsson, Joakim; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onogi, Kouta; Onyisi, Peter; Oppen, Henrik; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Otero y Garzon, Gustavo; Otono, Hidetoshi; Ouchrif, Mohamed; Ould-Saada, Farid; Ouraou, Ahmimed; Oussoren, Koen Pieter; Ouyang, Qun; Owen, Mark; Owen, Rhys Edward; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pachal, Katherine; 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Peschke, Richard; Peshekhonov, Vladimir; Peters, Krisztian; Peters, Yvonne; Petersen, Brian; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petroff, Pierre; Petrolo, Emilio; Petrov, Mariyan; Petrucci, Fabrizio; Pettersson, Nora Emilia; Peyaud, Alan; Pezoa, Raquel; Phillips, Forrest Hays; Phillips, Peter William; Piacquadio, Giacinto; Pianori, Elisabetta; Picazio, Attilio; Pickering, Mark Andrew; Piegaia, Ricardo; Pilcher, James; Pilkington, Andrew; Pinamonti, Michele; Pinfold, James; Pirumov, Hayk; Pitt, Michael; Plazak, Lukas; Pleier, Marc-Andre; Pleskot, Vojtech; Plotnikova, Elena; Pluth, Daniel; Podberezko, Pavel; Poettgen, Ruth; Poggi, Riccardo; Poggioli, Luc; Pogrebnyak, Ivan; Pohl, David-leon; Pokharel, Ishan; Polesello, Giacomo; Poley, Anne-luise; Policicchio, Antonio; Polifka, Richard; Polini, Alessandro; Pollard, Christopher Samuel; Polychronakos, Venetios; Pommès, Kathy; Ponomarenko, Daniil; Pontecorvo, Ludovico; Popeneciu, Gabriel Alexandru; Portillo Quintero, Dilia María; Pospisil, Stanislav; Potamianos, Karolos; Potrap, Igor; Potter, Christina; Potti, Harish; Poulsen, Trine; Poveda, Joaquin; Pozo Astigarraga, Mikel Eukeni; Pralavorio, Pascal; Pranko, Aliaksandr; Prell, Soeren; Price, Darren; Primavera, Margherita; Prince, Sebastien; Proklova, Nadezda; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Przybycien, Mariusz; Puri, Akshat; Puzo, Patrick; Qian, Jianming; Qin, Gang; Qin, Yang; Quadt, Arnulf; Queitsch-Maitland, Michaela; Quilty, Donnchadha; Raddum, Silje; Radeka, Veljko; Radescu, Voica; Radhakrishnan, Sooraj Krishnan; Radloff, Peter; Rados, Pere; Ragusa, Francesco; Rahal, Ghita; Raine, John Andrew; Rajagopalan, Srinivasan; Rangel-Smith, Camila; Rashid, Tasneem; Raspopov, Sergii; Ratti, Maria Giulia; Rauch, Daniel; Rauscher, Felix; Rave, Stefan; Ravinovich, Ilia; Rawling, Jacob Henry; Raymond, Michel; Read, Alexander Lincoln; Readioff, Nathan Peter; Reale, Marilea; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reed, Robert; Reeves, Kendall; Rehnisch, Laura; Reichert, Joseph; Reiss, Andreas; Rembser, Christoph; Ren, Huan; Rescigno, Marco; Resconi, Silvia; Resseguie, Elodie Deborah; Rettie, Sebastien; Reynolds, Elliot; Rezanova, Olga; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter, Stefan; Richter-Was, Elzbieta; Ricken, Oliver; Ridel, Melissa; Rieck, Patrick; Riegel, Christian Johann; Rieger, Julia; Rifki, Othmane; Rijssenbeek, Michael; Rimoldi, Adele; Rimoldi, Marco; Rinaldi, Lorenzo; Ripellino, Giulia; Ristić, Branislav; Ritsch, Elmar; Riu, Imma; Rizatdinova, Flera; Rizvi, Eram; Rizzi, Chiara; Roberts, Rhys Thomas; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocco, Elena; Roda, Chiara; Rodina, Yulia; Rodriguez Bosca, Sergi; Rodriguez Perez, Andrea; Rodriguez Rodriguez, Daniel; Roe, Shaun; Rogan, Christopher Sean; Røhne, Ole; Roloff, Jennifer; Romaniouk, Anatoli; Romano, Marino; Romano Saez, Silvestre Marino; Romero Adam, Elena; Rompotis, Nikolaos; Ronzani, Manfredi; Roos, Lydia; Rosati, Stefano; Rosbach, Kilian; Rose, Peyton; Rosien, Nils-Arne; Rossi, Elvira; Rossi, Leonardo Paolo; Rosten, Jonatan; Rosten, Rachel; Rotaru, Marina; Rothberg, Joseph; Rousseau, David; Roy, Debarati; Rozanov, Alexandre; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rurikova, Zuzana; Rusakovich, Nikolai; Russell, Heather; Rutherfoord, John; Ruthmann, Nils; Rüttinger, Elias Michael; Ryabov, Yury; Rybar, Martin; Rybkin, Grigori; Ryu, Soo; Ryzhov, Andrey; Rzehorz, Gerhard Ferdinand; Saavedra, Aldo; Sabato, Gabriele; Sacerdoti, Sabrina; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Saha, Puja; Sahinsoy, Merve; Saimpert, Matthias; Saito, Masahiko; Saito, Tomoyuki; Sakamoto, Hiroshi; Sakurai, Yuki; Salamanna, Giuseppe; Salazar Loyola, Javier Esteban; Salek, David; Sales De Bruin, Pedro Henrique; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sammel, Dirk; Sampsonidis, Dimitrios; Sampsonidou, Despoina; Sánchez, Javier; Sanchez Martinez, Victoria; Sanchez Pineda, Arturo Rodolfo; Sandaker, Heidi; Sandbach, Ruth Laura; Sander, Christian Oliver; Sandhoff, Marisa; Sandoval, Carlos; Sankey, Dave; Sannino, Mario; Sano, Yuta; Sansoni, Andrea; Santoni, Claudio; Santos, Helena; Santoyo Castillo, Itzebelt; Sapronov, Andrey; Saraiva, João; Sarrazin, Bjorn; Sasaki, Osamu; Sato, Koji; Sauvan, Emmanuel; Savage, Graham; Savard, Pierre; Savic, Natascha; Sawyer, Craig; Sawyer, Lee; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scanlon, Tim; Scannicchio, Diana; Schaarschmidt, Jana; Schacht, Peter; Schachtner, Balthasar Maria; Schaefer, Douglas; Schaefer, Leigh; Schaefer, Ralph; Schaeffer, Jan; Schaepe, Steffen; Schaetzel, Sebastian; Schäfer, Uli; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R Dean; Schegelsky, Valery; Scheirich, Daniel; Schenck, Ferdinand; Schernau, Michael; Schiavi, Carlo; Schier, Sheena; Schildgen, Lara Katharina; Schillo, Christian; Schioppa, Marco; Schlenker, Stefan; Schmidt-Sommerfeld, Korbinian Ralf; Schmieden, Kristof; Schmitt, Christian; Schmitt, Stefan; Schmitz, Simon; Schnoor, Ulrike; Schoeffel, Laurent; Schoening, Andre; Schoenrock, Bradley Daniel; Schopf, Elisabeth; Schott, Matthias; Schouwenberg, Jeroen; Schovancova, Jaroslava; Schramm, Steven; Schuh, Natascha; Schulte, Alexandra; Schultens, Martin Johannes; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwartzman, Ariel; Schwarz, Thomas Andrew; Schweiger, Hansdieter; Schwemling, Philippe; Schwienhorst, Reinhard; Schwindling, Jerome; Sciandra, Andrea; Sciolla, Gabriella; Scornajenghi, Matteo; Scuri, Fabrizio; Scutti, Federico; Searcy, Jacob; Seema, Pienpen; Seidel, Sally; Seiden, Abraham; Seixas, José; Sekhniaidze, Givi; Sekhon, Karishma; Sekula, Stephen; Semprini-Cesari, Nicola; Senkin, Sergey; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Sessa, Marco; Seuster, Rolf; Severini, Horst; Šfiligoj, Tina; Sforza, Federico; Sfyrla, Anna; Shabalina, Elizaveta; Shaikh, Nabila Wahab; Shan, Lianyou; Shang, Ruo-yu; Shank, James; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Shaw, Savanna Marie; Shcherbakova, Anna; Shehu, Ciwake Yusufu; Shen, Yu-Ting; Sherafati, Nima; Sherman, Alexander David; Sherwood, Peter; Shi, Liaoshan; Shimizu, Shima; Shimmin, Chase Owen; Shimojima, Makoto; Shipsey, Ian Peter Joseph; Shirabe, Shohei; Shiyakova, Mariya; Shlomi, Jonathan; Shmeleva, Alevtina; Shoaleh Saadi, Diane; Shochet, Mel; Shojaii, Seyed Ruhollah; Shope, David Richard; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sickles, Anne Marie; Sidebo, Per Edvin; Sideras Haddad, Elias; Sidiropoulou, Ourania; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silva, José; Silverstein, Samuel; Simak, Vladislav; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simon, Manuel; Sinervo, Pekka; Sinev, Nikolai; Sioli, Maximiliano; Siragusa, Giovanni; Siral, Ismet; Sivoklokov, Serguei; Sjölin, Jörgen; Skinner, Malcolm Bruce; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Slawinska, Magdalena; Sliwa, Krzysztof; Slovak, Radim; Smakhtin, Vladimir; Smart, Ben; Smiesko, Juraj; Smirnov, Nikita; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Joshua Wyatt; Smith, Matthew; Smith, Russell; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snyder, Ian Michael; Snyder, Scott; Sobie, Randall; Socher, Felix; Soffer, Abner; Søgaard, Andreas; Soh, Dart-yin; Sokhrannyi, Grygorii; Solans Sanchez, Carlos; Solar, Michael; Soldatov, Evgeny; Soldevila, Urmila; Solodkov, Alexander; Soloshenko, Alexei; Solovyanov, Oleg; Solovyev, Victor; Sommer, Philip; Son, Hyungsuk; Sopczak, Andre; Sosa, David; Sotiropoulou, Calliope Louisa; Sottocornola, Simone; Soualah, Rachik; Soukharev, Andrey; South, David; Sowden, Benjamin; Spagnolo, Stefania; Spalla, Margherita; Spangenberg, Martin; Spanò, Francesco; Sperlich, Dennis; Spettel, Fabian; Spieker, Thomas Malte; Spighi, Roberto; Spigo, Giancarlo; Spiller, Laurence Anthony; Spousta, Martin; St Denis, Richard Dante; Stabile, Alberto; Stamen, Rainer; Stamm, Soren; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanitzki, Marcel Michael; Stapf, Birgit Sylvia; Stapnes, Steinar; Starchenko, Evgeny; Stark, Giordon; Stark, Jan; Stark, Simon Holm; Staroba, Pavel; Starovoitov, Pavel; Stärz, Steffen; Staszewski, Rafal; Stegler, Martin; Steinberg, Peter; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stevenson, Thomas James; Stewart, Graeme; Stockton, Mark; Stoebe, Michael; Stoicea, Gabriel; Stolte, Philipp; Stonjek, Stefan; Stradling, Alden; Straessner, Arno; Stramaglia, Maria Elena; Strandberg, Jonas; Strandberg, Sara; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Stroynowski, Ryszard; Strubig, Antonia; Stucci, Stefania Antonia; Stugu, Bjarne; Styles, Nicholas Adam; Su, Dong; Su, Jun; Suchek, Stanislav; Sugaya, Yorihito; Suk, Michal; Sulin, Vladimir; Sultan, D M S; Sultansoy, Saleh; Sumida, Toshi; Sun, Siyuan; Sun, Xiaohu; Suruliz, Kerim; Suster, Carl; Sutton, Mark; Suzuki, Shota; Svatos, Michal; Swiatlowski, Maximilian; Swift, Stewart Patrick; Sykora, Ivan; Sykora, Tomas; Ta, Duc; Tackmann, Kerstin; Taenzer, Joe; Taffard, Anyes; Tafirout, Reda; Tahirovic, Elvedin; Taiblum, Nimrod; Takai, Helio; Takashima, Ryuichi; Takasugi, Eric Hayato; Takeda, Kosuke; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tanaka, Junichi; Tanaka, Masahiro; Tanaka, Reisaburo; Tanaka, Shuji; Tanioka, Ryo; Tannenwald, Benjamin Bordy; Tapia Araya, Sebastian; Tapprogge, Stefan; Tarem, Shlomit; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tashiro, Takuya; Tassi, Enrico; Tavares Delgado, Ademar; Tayalati, Yahya; Taylor, Aaron; Taylor, Alan James; Taylor, Geoffrey; Taylor, Pierre Thor Elliot; Taylor, Wendy; Teixeira-Dias, Pedro; Temple, Darren; Ten Kate, Herman; Teng, Ping-Kun; Teoh, Jia Jian; Tepel, Fabian-Phillipp; Terada, Susumu; Terashi, Koji; Terron, Juan; Terzo, Stefano; Testa, Marianna; Teuscher, Richard; Thais, Savannah Jennifer; Theveneaux-Pelzer, Timothée; Thiele, Fabian; Thomas, Juergen; Thomas-Wilsker, Joshuha; Thompson, Paul; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Tian, Yun; Tibbetts, Mark James; Ticse Torres, Royer Edson; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tisserant, Sylvain; Todome, Kazuki; Todorova-Nova, Sharka; Todt, Stefanie; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tolley, Emma; Tomlinson, Lee; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tong, Baojia(Tony); Tornambe, Peter; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Treado, Colleen Jennifer; Trefzger, Thomas; Tresoldi, Fabio; Tricoli, Alessandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Trofymov, Artur; Troncon, Clara; Trottier-McDonald, Michel; Trovatelli, Monica; Truong, Loan; Trzebinski, Maciej; Trzupek, Adam; Tsang, Ka Wa; Tseng, Jeffrey; Tsiareshka, Pavel; Tsirintanis, Nikolaos; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsuno, Soshi; Tsybychev, Dmitri; Tu, Yanjun; Tudorache, Alexandra; Tudorache, Valentina; Tulbure, Traian Tiberiu; Tuna, Alexander Naip; Turchikhin, Semen; Turgeman, Daniel; Turk Cakir, Ilkay; Turra, Ruggero; Tuts, Michael; Ucchielli, Giulia; Ueda, Ikuo; Ughetto, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Ungaro, Francesca; Unno, Yoshinobu; Uno, Kenta; Unverdorben, Christopher; Urban, Jozef; Urquijo, Phillip; Urrejola, Pedro; Usai, Giulio; Usui, Junya; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vadla, Knut Oddvar Hoie; Vaidya, Amal; Valderanis, Chrysostomos; Valdes Santurio, Eduardo; Valente, Marco; Valentinetti, Sara; Valero, Alberto; Valéry, Lo\\"ic; Valkar, Stefan; Vallier, Alexis; Valls Ferrer, Juan Antonio; Van Den Wollenberg, Wouter; van der Graaf, Harry; van Gemmeren, Peter; Van Nieuwkoop, Jacobus; van Vulpen, Ivo; van Woerden, Marius Cornelis; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vardanyan, Gagik; Vari, Riccardo; Varnes, Erich; Varni, Carlo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vasquez, Jared Gregory; Vasquez, Gerardo; Vazeille, Francois; Vazquez Furelos, David; Vazquez Schroeder, Tamara; Veatch, Jason; Veeraraghavan, Venkatesh; Veloce, Laurelle Maria; Veloso, Filipe; Veneziano, Stefano; Ventura, Andrea; Venturi, Manuela; Venturi, Nicola; Venturini, Alessio; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Ambrosius Thomas; Vermeulen, Jos; Vetterli, Michel; Viaux Maira, Nicolas; Viazlo, Oleksandr; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Vigani, Luigi; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinogradov, Vladimir; Vishwakarma, Akanksha; Vittori, Camilla; Vivarelli, Iacopo; Vlachos, Sotirios; Vogel, Marcelo; Vokac, Petr; Volpi, Guido; von der Schmitt, Hans; von Toerne, Eckhard; Vorobel, Vit; Vorobev, Konstantin; Vos, Marcel; Voss, Rudiger; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Peter; Wagner, Wolfgang; Wagner-Kuhr, Jeannine; Wahlberg, Hernan; Wahrmund, Sebastian; Wakamiya, Kotaro; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wallangen, Veronica; Wang, Chao; Wang, Chao; Wang, Fuquan; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Qing; Wang, Renjie; Wang, Rui; Wang, Song-Ming; Wang, Tingting; Wang, Wei; Wang, Wenxiao; Wang, Zirui; Wanotayaroj, Chaowaroj; Warburton, Andreas; Ward, Patricia; Wardrope, David Robert; Washbrook, Andrew; Watkins, Peter; Watson, Alan; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Ben; Webb, Aaron Foley; Webb, Samuel; Weber, Michele; Weber, Sebastian Mario; Weber, Stefan Wolf; Weber, Stephen; Webster, Jordan S; Weidberg, Anthony; Weinert, Benjamin; Weingarten, Jens; Weirich, Marcel; Weiser, Christian; Weits, Hartger; Wells, Phillippa; Wenaus, Torre; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Michael David; Werner, Per; Wessels, Martin; Weston, Thomas; Whalen, Kathleen; Whallon, Nikola Lazar; Wharton, Andrew Mark; White, Aaron; White, Andrew; White, Martin; White, Ryan; Whiteson, Daniel; Whitmore, Ben William; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wildauer, Andreas; Wilk, Fabian; Wilkens, Henric George; Williams, Hugh; Williams, Sarah; Willis, Christopher; Willocq, Stephane; Wilson, John; Wingerter-Seez, Isabelle; Winkels, Emma; Winklmeier, Frank; Winston, Oliver James; Winter, Benedict Tobias; Wittgen, Matthias; Wobisch, Markus; Wolf, Anton; Wolf, Tim Michael Heinz; Wolff, Robert; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Vincent Wai Sum; Woods, Natasha Lee; Worm, Steven; Wosiek, Barbara; Wotschack, Jorg; Wozniak, Krzysztof; Wu, Miles; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wyatt, Terry Richard; Wynne, Benjamin; Xella, Stefania; Xi, Zhaoxu; Xia, Ligang; Xu, Da; Xu, Lailin; Xu, Tairan; Xu, Wenhao; Yabsley, Bruce; Yacoob, Sahal; Yamaguchi, Daiki; Yamaguchi, Yohei; Yamamoto, Akira; Yamamoto, Shimpei; Yamanaka, Takashi; Yamane, Fumiya; Yamatani, Masahiro; Yamazaki, Tomohiro; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Hongtao; Yang, Yi; Yang, Zongchang; Yao, Weiming; Yap, Yee Chinn; Yasu, Yoshiji; Yatsenko, Elena; Yau Wong, Kaven Henry; Ye, Jingbo; Ye, Shuwei; Yeletskikh, Ivan; Yigitbasi, Efe; Yildirim, Eda; Yorita, Kohei; Yoshihara, Keisuke; Young, Charles; Young, Christopher John; Yu, Jaehoon; Yu, Jie; Yuen, Stephanie P; Yusuff, Imran; Zabinski, Bartlomiej; Zacharis, Georgios; Zaidan, Remi; Zaitsev, Alexander; Zakharchuk, Nataliia; Zalieckas, Justas; Zaman, Aungshuman; Zambito, Stefano; Zanzi, Daniele; Zeitnitz, Christian; Zemaityte, Gabija; Zemla, Andrzej; Zeng, Jian Cong; Zeng, Qi; Zenin, Oleg; Ženiš, Tibor; Zerwas, Dirk; Zhang, Dengfeng; Zhang, Dongliang; Zhang, Fangzhou; Zhang, Guangyi; Zhang, Huijun; Zhang, Jinlong; Zhang, Lei; Zhang, Liqing; Zhang, Matt; Zhang, Peng; Zhang, Rui; Zhang, Ruiqi; Zhang, Xueyao; Zhang, Yu; Zhang, Zhiqing; Zhao, Xiandong; Zhao, Yongke; Zhao, Zhengguo; Zhemchugov, Alexey; Zhou, Bing; Zhou, Chen; Zhou, Li; Zhou, Maosen; Zhou, Mingliang; Zhou, Ning; Zhou, You; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhukov, Konstantin; Zibell, Andre; Zieminska, Daria; Zimine, Nikolai; Zimmermann, Christoph; Zimmermann, Stephanie; Zinonos, Zinonas; Zinser, Markus; Ziolkowski, Michael; Živković, Lidija; Zobernig, Georg; Zoccoli, Antonio; Zou, Rui; zur Nedden, Martin; Zwalinski, Lukasz

    2017-01-01

    A search for the exclusive decays of the Higgs and $Z$ bosons to a $\\phi$ or $\\rho$ meson and a photon is performed with a $pp$ collision data sample corresponding to an integrated luminosity of up to 35.6 $fb^{-1}$ collected at $\\sqrt{s}=13$ TeV with the ATLAS detector at the CERN Large Hadron Collider. These decays have been suggested as a probe of the Higgs boson couplings to light quarks. No significant excess of events is observed above the background, as expected from the Standard Model. Upper limits at 95% confidence level were obtained on the branching fractions of the Higgs boson decays to $\\phi\\gamma$ and $\\rho\\gamma$ of $4.8\\times10^{-4}$ and $8.8\\times10^{-4}$, respectively. The corresponding 95% confidence level upper limits for the $Z$ boson decays are $0.9\\times10^{-6}$ and $25\\times10^{-6}$ for $\\phi\\gamma$ and $\\rho\\gamma$, respectively.

  9. Diffractive production of two {rho}{sup 0} {sub L} mesons in e{sup +}e{sup -} collisions

    Energy Technology Data Exchange (ETDEWEB)

    Segond, M.; Wallon, S. [Universite Paris-Sud - CNRS, LPT, Orsay (France); Szymanowski, L. [Universite Paris-Sud - CNRS, LPT, Orsay (France); Soltan Institute for Nuclear Studies, Warsaw (Poland); Universite de Liege, Liege (Belgium); Ecole Polytechnique - CNRS, CPHT, Palaiseau (France)

    2007-09-15

    We present an estimate of the cross-section for the exclusive production of a {rho}{sub L}{sup 0}-meson pair in e{sup +}e{sup -} scattering, which will be studied in the future high-energy International Linear Collider. For this aim, we complete calculations of the Born order approximation of the amplitudes {gamma}{sup *}{sub L,T}(Q{sub 1}{sup 2}){gamma}{sup *}{sub L,T}(Q{sub 2}{sup 2}){yields}{rho}{sub L}{sup 0}{rho}{sub L}{sup 0}, for arbitrary polarization of virtual photons and longitudinally polarized mesons, in the kinematical region s>>-t,Q{sub 1} {sup 2},Q{sub 2} {sup 2}. These processes are completely calculable in the hard region Q{sub 1}{sup 2},Q{sub 2}{sup 2}>>{lambda}{sup 2}{sub QCD}, and we perform most of the calculations in an analytical way. The resulting cross-section turns out to be large enough for this process to be measurable with foreseen luminosity and energy, for Q{sub 1}{sup 2} and Q{sub 2}{sup 2} in the range of a few GeV{sup 2}. (orig.)

  10. RhoA mediates the expression of acidic extracellular pH-induced matrix metalloproteinase-9 mRNA through phospholipase D1 in mouse metastatic B16-BL6 melanoma cells.

    Science.gov (United States)

    Maeda, Toyonobu; Yuzawa, Satoshi; Suzuki, Atsuko; Baba, Yuh; Nishimura, Yukio; Kato, Yasumasa

    2016-03-01

    Solid tumors are characterized by acidic extracellular pH (pHe). The present study examined the contribution of small GTP-binding proteins to phospholipase D (PLD) activation of acidic pHe-induced matrix metalloproteinase-9 (MMP-9) production. Acidic pHe-induced MMP-9 production was reduced by C3 exoenzyme, which inhibits the Rho family of GTPases; cytochalasin D, which inhibits actin reorganization; and simvastatin, which inhibits geranylgeranylation of Rho. Small interfering RNA (siRNA) against RhoA, but not against Rac1 or Cdc42, significantly inhibited acidic pHe induction of MMP-9. Pull-down assays showed that acidic pHe increased the activated form of RhoA. Forced expression of constitutively active RhoA induced MMP-9 production, even at neutral pHe. RhoA siRNA also reduced acidic pHe induced PLD activity. Specific inhibition of PLD1 and Pld1 gene knockout significantly reduced acidic pHe-induced MMP-9 expression. In contrast, PLD2 inhibition or knockout had no effect on MMP-9 expression. These findings suggested that RhoA-PLD1 signaling is involved in acidic pHe induction of MMP-9.

  11. Transverse target-spin asymmetry in exclusive electroproduction of {rho}{sup 0} mesons

    Energy Technology Data Exchange (ETDEWEB)

    Dreschler, Jeroen

    2008-10-15

    This thesis reports the first measurements of the asymmetry in exclusive {rho}{sup 0} electroproduction from a transversely polarized proton. The asymmetry was extracted from data taken by the HERMES experiment at DESY with a polarized internal hydrogen gas target and the 27.6 GeV electron (positron) beam of HERA. (orig.)

  12. Mechanical stimuli on C2C12 myoblasts affect myoblast differentiation, focal adhesion kinase phosphorylation and galectin-1 expression

    DEFF Research Database (Denmark)

    Grossi, Alberto Blak; Lametsch, Rene; Karlsson, Anders H

    2011-01-01

    Mechanical forces are crucial in the regulation of cell morphology and function. At the cellular level, these forces influence myoblast differentiation and fusion. In this study we applied mechanical stimuli to embryonic muscle cells using magnetic microbeads, a method shown to apply stress...... by mechanical stimulation including Galectin-1, Annexin III, and RhoGDI. In this study we demonstrate how the combination of this method of mechanical stimuli and proteomic analysis can be a powerful tool to detect proteins that are potentially interacting in biochemical pathways or complex cellular mechanisms...... during the process of myoblast differentiation. We determined an increase in expression and changes in cellular localization of Galectin-1, in mechanically stimulated myoblasts. A potential involvement of Galectin-1 in myoblast differentiation is presented....

  13. The fibronectin-binding integrins alpha5beta1 and alphavbeta3 differentially modulate RhoA-GTP loading, organization of cell matrix adhesions, and fibronectin fibrillogenesis

    DEFF Research Database (Denmark)

    Danen, Erik H J; Sonneveld, Petra; Brakebusch, Cord

    2002-01-01

    We have studied the formation of different types of cell matrix adhesions in cells that bind to fibronectin via either alpha5beta1 or alphavbeta3. In both cases, cell adhesion to fibronectin leads to a rapid decrease in RhoA activity. However, alpha5beta1 but not alphavbeta3 supports high levels ...... receptors expressed on a cell dictates the ability of fibronectin to stimulate RhoA-mediated organization of cell matrix adhesions.......We have studied the formation of different types of cell matrix adhesions in cells that bind to fibronectin via either alpha5beta1 or alphavbeta3. In both cases, cell adhesion to fibronectin leads to a rapid decrease in RhoA activity. However, alpha5beta1 but not alphavbeta3 supports high levels...... of RhoA activity at later stages of cell spreading, which are associated with a translocation of focal contacts to peripheral cell protrusions, recruitment of tensin into fibrillar adhesions, and fibronectin fibrillogenesis. Expression of an activated mutant of RhoA stimulates alphavbeta3-mediated...

  14. Measurement of the branching fractions for B0 -->D*-pi+ and B0 -->D*rho+

    Energy Technology Data Exchange (ETDEWEB)

    Barrera, Barbara

    2000-10-13

    Using 5.2 fb{sup -1} annihilation data recorded with the BABAR detector at the PEP-II storage ring while operating on the {Upsilon}(4S) resonance, a sample of fully reconstructed B{sup 0} decays in the hadronic modes B{sup 0} {yields} D*{sup -} {pi}{sup +} and B{sup 0} {yields} D*{sup -} {rho}{sup +} have been reconstructed. In this paper, a study of these events is reported, including preliminary measurements of the absolute branching fractions for these modes, which are found to be B(B{sup 0} {yields} D*{sup -} {pi}{sup +} = 2.9 {+-} 0.3 {+-} 0.3) x 10{sup -3} and B(B{sup 0} {yields} D*{sup -} {rho}{sup +}) = (11.2 {+-} 1.1 {+-} 2.5) x 10{sup -3}.

  15. Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway.

    Science.gov (United States)

    Zhao, Zhongyan; Gong, Shilin; Wang, Shumin; Ma, Chunhua

    2015-09-01

    Evodiamine (EVD), a major alkaloid compound extracted from the dry unripened fruit Evodia fructus (Evodia rutaecarpa Benth., Rutaceae), has various pharmacological effects. The purpose of the present study was to investigate the possible anti-ulcerogenic potential of EVD and explore the underlying mechanism against ethanol-induced gastric ulcer in mice. Administration of EVD at the doses of 20, 40mg/kg body weight prior to the ethanol ingestion could effectively protect the stomach from ulceration. The gastric lesion was significantly ameliorated in the EVD group compared with that in the model group. Pre-treatment with EVD prevented the oxidative damage and decreased the levels of prostaglandin E2 (PGE2) content, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, EVD pretreatment markedly increased the serum levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), decreased malonaldehyde (MDA) content in serum and activity of myeloperoxidase (MPO) in stomach tissues compared with those in the model group. In the mechanistic study, significant elevation of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 expressions were observed in the gastric mucosa group, whereas EVD effectively suppressed the protein expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 in mice. Moreover, EVD showed protective activity on ethanol-induced GES-1 cells, while the therapeutic effects were not due to its cytotoxity. Taken together, these results strongly indicated that EVD exerted a gastro-protective effect against gastric ulceration. The underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through Rho/NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Gallic acid inhibits gastric cancer cells metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-κB activity

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Hsieh-Hsun [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Chi-Sen [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 402, Taiwan (China); Ho, Wei-Chi [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China); Liao, Sheng-You [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Lin, Wea-Lung [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Wang, Chau-Jong, E-mail: wcj@csmu.edu.tw [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China)

    2013-01-01

    Our previous study demonstrated the therapeutic potential of gallic acid (GA) for controlling tumor metastasis through its inhibitory effect on the motility of AGS cells. A noteworthy finding in our previous experiment was increased RhoB expression in GA-treated cells. The aim of this study was to evaluate the role of RhoB expression on the inhibitory effects of GA on AGS cells. By applying the transfection of RhoB siRNA into AGS cells and an animal model, we tested the effect of GA on inhibition of tumor growth and RhoB expression. The results confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells’ invasive growth involving blocking the AKT/small GTPase signals pathway and inhibition of NF-κB activity. Finally, we evaluated the effect of GA on AGS cell metastasis by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells growth via the expression of RhoB. These data support the inhibitory effect of GA which was shown to inhibit gastric cancer cell metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-κB activity. Thus, GA might be a potential agent in treating gastric cancer. Highlights: ► GA could downregulate AKT signal via increased expression of RhoB. ► GA inhibits metastasis in vitro in gastric carcinoma. ► GA inhibits tumor growth in nude mice model.

  17. QCD factorization beyond leading twist in exclusive processes: rhoT-meson production

    International Nuclear Information System (INIS)

    Wallon, S.; Anikin, I.; ); Ivanov, D.; Pire, B.; Szymanowski, L.

    2009-01-01

    Exclusive processes in hard electroproduction with asymptotic γ * p center of mass energy is one of the best place for understanding QCD in the perturbative Regge limit. The HERA experiment recently provided precise data for rho electroproduction, including all spin density matrix elements. From QCD, it is expected that such a process should factorize between a hard (calculable) coefficient function, and hadronic (P and ρ) matrix elements. Such a factorization is up to now only proven for a longitudinally polarized rho. Within the kt-factorization approach (valid at large s γ * p), we evaluate the impact factor of the transition γ * → ρT taking into account the twist 3 contributions. We show that a gauge invariant expression is obtained with the help of QCD equations of motion. More generally, relying on these equations and on the gauge invariance of the factorized amplitude, the non-perturbative Distribution Amplitudes can be reduced to a minimal set. This opens the way to a consistent treatment of factorization for exclusive processes with a transversally polarized vector meson. (author)

  18. Thiopurine Prodrugs Mediate Immunosuppressive Effects by Interfering with Rac1 Protein Function*

    Science.gov (United States)

    Shin, Jin-Young; Wey, Michael; Umutesi, Hope G.; Sun, Xiangle; Simecka, Jerry; Heo, Jongyun

    2016-01-01

    6-Thiopurine (6-TP) prodrugs include 6-thioguanine and azathioprine. Both are widely used to treat autoimmune disorders and certain cancers. This study showed that a 6-thioguanosine triphosphate (6-TGTP), converted in T-cells from 6-TP, targets Rac1 to form a disulfide adduct between 6-TGTP and the redox-sensitive GXXXXGK(S/T)C motif of Rac1. This study also showed that, despite the conservation of the catalytic activity of RhoGAP (Rho-specific GAP) on the 6-TGTP-Rac1 adduct to produce the biologically inactive 6-thioguanosine diphosphate (6-TGDP)-Rac1 adduct, RhoGEF (Rho-specific GEF) cannot exchange the 6-TGDP adducted on Rac1 with free guanine nucleotide. The biologically inactive 6-TGDP-Rac1 adduct accumulates in cells because of the ongoing combined actions of RhoGEF and RhoGAP. Because other Rho GTPases, such as RhoA and Cdc42, also possess the GXXXXGK(S/T)C motif, the proposed mechanism for the inactivation of Rac1 also applies to RhoA and Cdc42. However, previous studies have shown that CD3/CD28-stimulated T-cells contain more activated Rac1 than other Rho GTPases such as RhoA and Cdc42. Accordingly, Rac1 is the main target of 6-TP in activated T-cells. This explains the T-cell-specific Rac1-targeting therapeutic action of 6-TP that suppresses the immune response. This proposed mechanism for the action of 6-TP on Rac1 performs a critical role in demonstrating the capability to design a Rac1-targeting chemotherapeutic agent(s) for autoimmune disorders. Nevertheless, the results also suggest that the targeting action of other Rho GTPases in other organ cells, such as RhoA in vascular cells, may be linked to cytotoxicities because RhoA plays a key role in vasculature functions. PMID:27189938

  19. Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors.

    Science.gov (United States)

    Goodman, Krista B; Cui, Haifeng; Dowdell, Sarah E; Gaitanopoulos, Dimitri E; Ivy, Robert L; Sehon, Clark A; Stavenger, Robert A; Wang, Gren Z; Viet, Andrew Q; Xu, Weiwei; Ye, Guosen; Semus, Simon F; Evans, Christopher; Fries, Harvey E; Jolivette, Larry J; Kirkpatrick, Robert B; Dul, Edward; Khandekar, Sanjay S; Yi, Tracey; Jung, David K; Wright, Lois L; Smith, Gary K; Behm, David J; Bentley, Ross; Doe, Christopher P; Hu, Erding; Lee, Dennis

    2007-01-11

    Rho kinase (ROCK1) mediates vascular smooth muscle contraction and is a potential target for the treatment of hypertension and related disorders. Indazole amide 3 was identified as a potent and selective ROCK1 inhibitor but possessed poor oral bioavailability. Optimization of this lead resulted in the discovery of a series of dihydropyridones, exemplified by 13, with improved pharmacokinetic parameters relative to the initial lead. Indazole substitution played a critical role in decreasing clearance and improving oral bioavailability.

  20. Regulation of cerebral cortex development by Rho GTPases: insights from in vivo studies

    Directory of Open Access Journals (Sweden)

    Roberta eAzzarelli

    2015-01-01

    Full Text Available The cerebral cortex is the site of higher human cognitive and motor functions. Histologically, it is organized into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection neurons and inhibitory interneurons. The stereotyped cellular distribution of cortical neurons is crucial for the formation of functional neural circuits and it is predominantly established during embryonic development. Cortical neuron development is a multiphasic process characterized by sequential steps of neural progenitor proliferation, cell cycle exit, neuroblast migration and neuronal differentiation. This series of events requires an extensive and dynamic remodeling of the cell cytoskeleton at each step of the process. As major regulators of the cytoskeleton, the family of small Rho GTPases has been shown to play essential functions in cerebral cortex development. Here we review in vivo findings that support the contribution of Rho GTPases to cortical projection neuron development and we address their involvement in the etiology of cerebral cortex malformations.

  1. Domain Walls and Macroscopic Spin-Flip-Like States in GdxCo1-x/GdyCo1-y Bilayers

    Science.gov (United States)

    Martin, Jose I.

    2005-03-01

    Exchange coupled double layers (ECDL) made of rare earth -- transition metal amorphous alloys are of basic and technological interest, as they present different magnetization configurations when the composition is changed or when the temperature is varied crossing the compensation temperatures (Tcomp) of both ferrimagnetic alloys. In this work, amorphous GdxCo1-x(100 nm)/GdyCo1-y(100 nm) ECDL have been prepared to investigate the magnetization reversal and the stable magnetic configurations when the compositions of both layers are similar: x = 0.22, y = 0.24. The samples have been grown by co-sputtering on corning glass substrates, which has allowed to analyze the behaviour within each layer by transverse Kerr effect measurements. A rich variety of behaviours has been found in the temperature range between the Tcomp of both layers, including magnetization reversal by annihilation/creation of a Bloch wall across the sample thickness, and a macroscopic spin-flip-like metamagnetic state where the magnetic moments form a double antiferromagnetic state with the presence of a N'eel-like wall when the magnetizations of both layers are similar [1]. The whole observed behavior can be understood in terms of a deduced general magnetic field -- temperature phase diagram. [1] R. Morales et al. Phys. Rev. B 70, 174440 (2004). Work supported by Spanish CICYT.

  2. Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1

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    Junichiro Miyazaki

    2017-04-01

    Full Text Available Renal cell carcinoma (RCC is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1, was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046, Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084 and poor prognosis in RCC patients (P = .0345. Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149 of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.

  3. A novel role for inhibitor of apoptosis (IAP) proteins as regulators of endothelial barrier function by mediating RhoA activation.

    Science.gov (United States)

    Hornburger, Michael C; Mayer, Bettina A; Leonhardt, Stefanie; Willer, Elisabeth A; Zahler, Stefan; Beyerle, Andrea; Rajalingam, Krishnaraj; Vollmar, Angelika M; Fürst, Robert

    2014-04-01

    Inhibitor of apoptosis (IAP) proteins, such as XIAP or cIAP1/2, are important regulators of apoptosis in cancer cells, and IAP antagonists are currently evaluated as antitumor agents. Beyond their function in cancer cells, this study demonstrates a novel role of IAPs as regulators of vascular endothelial permeability. Two structurally different IAP antagonists, ABT and Smac085, as well as silencing of IAPs, reduced the thrombin receptor-activating peptide (TRAP)-induced barrier dysfunction in human endothelial cells as assessed by measuring macromolecular permeability or transendothelial electrical resistance. ABT diminished thrombin-evoked stress fiber formation, activation of myosin light chain 2, and disassembly of adherens junctions independent of calcium signaling, protein kinase C, and mitogen-activated protein kinases. Interestingly, ABT and silencing of IAPs, in particular XIAP, reduced the TRAP-evoked RhoA activation, whereas Rac1 was not affected. XIAP and, to a lesser extent, cIAP1 were found to directly interact with RhoA independently of the RhoA activation status. Under cell-free conditions, XIAP did not induce an ubiquitination of RhoA. In summary, our work discloses IAPs as crucial regulators of endothelial permeability and suggests IAP inhibition as interesting approach for the prevention of endothelial barrier dysfunction.

  4. Piezoelectric ceramic (PZT) modulates axonal guidance growth of rat cortical neurons via RhoA, Rac1, and Cdc42 pathways.

    Science.gov (United States)

    Wen, Jianqiang; Liu, Meili

    2014-03-01

    Electrical stimulation is critical for axonal connection, which can stimulate axonal migration and deformation to promote axonal growth in the nervous system. Netrin-1, an axonal guidance cue, can also promote axonal guidance growth, but the molecular mechanism of axonal guidance growth under indirect electric stimulation is still unknown. We investigated the molecular mechanism of axonal guidance growth under piezoelectric ceramic lead zirconate titanate (PZT) stimulation in the primary cultured cortical neurons. PZT induced marked axonal elongation. Moreover, PZT activated the excitatory postsynaptic currents (EPSCs) by increasing the frequency and amplitude of EPSCs of the cortical neurons in patch clamp assay. PZT downregulated the expression of Netrin-1 and its receptor Deleted in Colorectal Cancer (DCC). Rho GTPase signaling is involved in interactions of Netrin-1 and DCC. PZT activated RhoA. Dramatic decrease of Cdc42 and Rac1 was also observed after PZT treatment. RhoA inhibitor Clostridium botulinum C3 exoenzyme (C3-Exo) prevented the PZT-induced downregulation of Netrin-1 and DCC. We suggest that PZT can promote axonal guidance growth by downregulation of Netrin-1 and DCC to mediate axonal repulsive responses via the Rho GTPase signaling pathway. Obviously, piezoelectric materials may provide a new approach for axonal recovery and be beneficial for clinical therapy in the future.

  5. Novel anti-metastatic action of cidofovir mediated by inhibition of E6/E7, CXCR4 and Rho/ROCK signaling in HPV tumor cells.

    Directory of Open Access Journals (Sweden)

    Abdessamad Amine

    Full Text Available Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1alpha and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1alpha/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1alpha stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1 in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1alpha/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1alpha-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1alpha/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor. These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition.

  6. BRAF and RAS oncogenes regulate