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Sample records for core rho oph

  1. 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

  2. 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

  3. ROSAT X-ray sources embedded in the rho Ophiuchi cloud core

    Science.gov (United States)

    Casanova, Sophie; Montmerle, Thierry; Feigelson, Eric D.; Andre, Philippe

    1995-02-01

    We present a deep ROSAT Position Sensitive Proportional Counter (PSPC) image of the central region of the rho Oph star-forming region. The selected area, about 35 x 35 arcmins in size, is rich with dense molecular cores and young stellar objects (YSOs). Fifty-five reliable X-ray sources are detected (and up to 50 more candidates may be present) above approximately 1 keV,, doubling the number of Einstein sources in this area. These sources are cross-identified with an updated list of 88 YSOs associated with the rho Oph cloud core. A third of the reliable X-ray sources do not have optical counterparts on photographic plates. Most can be cross-identified wth Class II and Class III infrared (IR) sources, which are embedded T Tauri stars, but three reliable X-ray sources and up to seven candidate sources are tentatively identified with Class I protostars. Eighteen reliable, and up to 20 candidate, X-ray sources are probably new cloud members. The overall detection rate of the bona fide cloud population is very high (73% for the Class II and Class III objects). The spatial distribution of the X-ray sources closely follows that of the moleclar gas. The visual extinctions Av estimated from near-IR data) of the ROSAT sources can be as high as 50 or more, confirming that most are embedded in the cloud core and are presumably very young. Using bolometric luminosities Lbol estimated from J-magnitudes a tight correlation between Lx and Lbol is found, similar to that seen for older T Tauri stars in the Cha I cloud: Lx approximately 10-4 Lbol. A general relation Lxproportional to LbolLj seems to apply to all T Tauri-like YSOs. The near equality of the extintion in the IR J band and in the keV X-ray rage implies that this relation is valid for the detected fluxes as well as for the dereddened fluxes. The X-ray luminosity function of the embedded sourced in rho Oph spans a range of Lx approximately 1028.5 to approximately equal to or greater than 1031.5 ergs/s and is statistically

  4. 2 Centimeter H2CO emission in the rho Ophiuchi cloud

    International Nuclear Information System (INIS)

    Loren, R.B.; Wootten, A.; Sandqvist, A.; Bernes, C.

    1980-01-01

    Strong emission in the 2 cm J-1K 1 =2 12 --2 11 line of H 2 CO has been found in the rho Oph dark cloud (rho Oph B). Previously this 2 cm H 2 CO line has been detected in emission only in the warm (T/sub K/>50 K) clouds OMC-1 and OMC-2. Densities in excess of 10 6 cm -3 are required to drive this 2 cm line into emission. The 2 mm J-1K 1 =2 12 --1 11 ortho-H 2 CO emission line at rho Oph B appears to be self-reversed when compared to optically thin lines (e.g., H 2 13 CO). The dense rho Oph B core has a mass of approx.100 M/sub sun/ and an extinction of A/sub v/>200 mag similar to OMC-1 or OMC-2, but differs from them in temperature, being a cold region emitting strong lines of DCO + . While near- and far-infrared and radio continuum searches cover the rho Oph B region, no known sources are coincident with the region of 2 cm H 2 CO emission. More sensitive searches are needed. The lack of observed signposts of star formation in an unusually dense cold region indicates rho Oph B may represent an earlier stage of cloud evolution than either the OMC-1 or OMC-2 regions

  5. Rho GTPases

    Science.gov (United States)

    Sadok, Amine; Marshall, Chris J

    2014-01-01

    Since their discovery in the late eighties, the role of Rho GTPases in the regulation of cell migration has been extensively studied and has mainly focused on the hallmark family members Rho, Rac, and Cdc42. Recent technological advances in cell biology, such as Rho-family GTPase activity biosensors, studies in 3D, and unbiased RNAi-based screens, have revealed an increasingly complex role for Rho GTPases during cell migration, with many inter-connected functions and a strong dependency on the physical and chemical properties of the surrounding environment. This review aims to give an overview of recent studies on the role of Rho-family GTPase members in the modulation of cell migration in different environments, and discuss future directions. PMID:24978113

  6. The Rho Termination Factor of Clostridium botulinum contains a Prion-Like Domain with a highly Amyloidogenic Core

    Directory of Open Access Journals (Sweden)

    Irantzu ePallares

    2016-01-01

    Full Text Available Prion-like proteins can switch between a soluble intrinsically disordered conformation and a highly ordered amyloid assembly. This conformational promiscuity is encoded in specific sequence regions, known as prion domains (PrDs. Prions are best known as the causative factors of neurological diseases in mammals. However, bioinformatics analyses reveal that proteins bearing PrDs are present in all kingdoms of life, including bacteria, thus supporting the idea that they serve conserved beneficial cellular functions. Despite the proportion of predicted prion-like proteins in bacterial proteomes is generally low, pathogenic species seem to have a higher prionic load, suggesting that these malleable proteins may favor pathogenic traits. In the present work, we performed a stringent computational analysis of the Clostridium botulinum pathogen proteome in the search for prion-like proteins. A total of 54 candidates were predicted for this anaerobic bacterium, including the transcription termination Rho factor. This RNA-binding protein has been shown to play a crucial role in bacterial adaptation to changing environments. We show here that the predicted disordered PrD domain of this RNA-binding protein contains an inner, highly polar, asparagine-rich short sequence able to spontaneously self-assemble into amyloid-like structures, bearing thus the potential to induce a Rho factor conformational switch that might rewire gene expression in response to environmental conditions.

  7. A Mid-Infrared Imaging Survey of Embedded Young Stellar Objects in the (rho) Ophiuchi Cloud Core

    Science.gov (United States)

    Barsony, Mary; Ressler, Michael E.; Marsh, Kenneth A.

    2005-01-01

    Results of a comprehensive, new, ground-based mid-infrared imaging survey of the young stellar population of the (rho) Ophiuchi cloud are presented. Data were acquired at the Palomar 5m and at the Keck 10m telescopes with the MIRLIN and LWS instruments, at 0'.5 and 0'.25 resolutions, respectively. Of 172 survey objects, 85 were detected. Among the 22 multiple systems observed, 15 were resolved and their individual component fluxes determined. A plot of the frequency distribution of the detected objects with SED spectral slope shows that YSOs spend approx.4 x 10(exp 5) yr in the flat-spectrum phase, clearing out their remnant infall envelopes. Mid-infrared variability is found among a significant fraction of the surveyed objects and is found to occur for all SED classes with optically thick disks. Large-amplitude near-infrared variability, also found for all SED classes with optically thick disks, seems to occur with somewhat higher frequency at the earlier evolutionary stages. Although a general trend of mid-infrared excess and near-infrared veiling exists progressing through SED classes, with Class I objects generally exhibiting r(sub K) >= 1, flat-spectrum objects with r(sub K) >= 0.58, and Class III objects with r(sub K) =0, Class II objects exhibit the widest range of r(sub K) values, ranging from 0 infrared versus near-infrared excesses in a subsample with well-determined effective temperatures and extinction values, disk-clearing mechanisms are explored. The results are consistent with disk clearing proceeding from the inside out.

  8. DETERMINISTIC COMPONENTS IN THE LIGHT CURVE AMPLITUDE OF Y OPH

    International Nuclear Information System (INIS)

    Pop, Alexandru; Turcu, Vlad; Vamos, Calin

    2010-01-01

    About two decades after the discovery of the amplitude decline of the light curve of the classical Cepheid Y Oph, its study is resumed using an increased amount of homogenized data and an extended time base. In our approach, the investigation of different time series concerning the light curve amplitude of Y Oph is not only the reason for the present study, but also a stimulus for developing a coherent methodology for studying long- and short-term variability phenomena in variable stars, taking into account the details of concrete observing conditions: amount of data, data sampling, time base, and individual errors of observational data. The statistical significance of this decreasing trend was estimated by assuming its linearity. We approached the decision-making process by formulating adequate null and alternative hypotheses, and testing the value of the regression line slope for different data sets via Monte Carlo simulations. A variability analysis, through various methods, of the original data and of the residuals obtained after removing the linear trend was performed. We also proposed a new statistical test, based on amplitude spectrum analysis and Monte Carlo simulations, intended to evaluate how detectible is a given (linear) trend in well-defined observing conditions: the trend detection probability. The main conclusion of our study on Y Oph is that, even if the false alarm probability is low enough to consider the decreasing trend to be statistically significant, the available data do not allow us to obtain a reasonably powerful test. We are able to confirm the light curve amplitude decline, and the order of magnitude of its slope with a better statistical substantiation. According to the obtained values of the trend detection probability, it seems that the trend we are dealing with is marked by a low detectibility. Our attempt to find signs of possible variability phenomena at shorter timescales ended by emphasizing the relative constancy of our data

  9. 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...

  10. Q-VE-OPh, a Negative Control for O-Phenoxy-Conjugated Caspase Inhibitors

    Directory of Open Access Journals (Sweden)

    Benjamin Southerland

    2010-06-01

    Full Text Available The broad-spectrum apoptosis (caspase inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibi- tor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh, thereby retaining the identical charge and molecular properties with only the addition of an extra –CH2 group. The purity and quality were assessed by ion trap mass spectrometry and verified by nuclear magnetic resonance. We determined the effectiveness of Q-VE-OPh, in comparison to Q-VD-OPh, to prevent DNA fragmentation in human Jurkat T leukemia cells that were induced to undergo apoptosis. DNA fragmentation was analyzed by agarose gel electrophoresis for the presence of DNA laddering, the hallmark indicator of apoptosis. Our results indicate that apoptosis was potently inhibited by Q-VD-OPh. In stark contrast, Q-VE-OPh did not inhibit apoptosis at a similar dose but required at least 20 times greater concentration than Q-VD-OPh to have any inhibitory effect. Western blot analysis showed that Q-VE-OPh was similarly less effective at inhibiting the activation of the extrinsic (caspase 8 and intrinsic (caspase 9 initiator caspases. Cell proliferation and viability studies further demonstrate that Q-VE-OPh is non-toxic, even at high concentration. Our data indicate that the specificity, effectiveness, and absence of toxicity of Q-VE-OPh provides the appropriate and superior negative control for in vitro and in vivo studies when analyzing the effects of o-phenoxy caspase inhibitors.

  11. Q-VE-OPh, a Negative Control for O-Phenoxy-Conjugated Caspase Inhibitors

    Directory of Open Access Journals (Sweden)

    Benjamin Southerland

    2010-01-01

    Full Text Available The broad-spectrum apoptosis (caspase inhibitor, Q-VD-OPh, has been shown to have no side effects and is effective at a much lower concentration than other FMK-type caspase inhibitors. However, an appropriate negative control to use with this inhibitor has not been available. In this study, we developed and analyzed a new compound, based on the Q-VD-OPh backbone, which acts as a cognate negative control. To create the negative control, we substituted a glutamate residue for the aspartate residue to create Q-VE-OPh , thereby retaining the identical charge and molecular properties with only the addition of an extra -CH2 group. The purity and quality were assessed by ion trap mass spectrometry and verified by nuclear magnetic resonance. We determined the effectiveness of Q-VE-OPh, in comparison to Q-VD-OPh, to prevent DNA fragmentation in human Jurkat T leukemia cells that were induced to undergo apoptosis. DNA fragmentation was analyzed by agarose gel electrophoresis for the presence of DNA laddering, the hallmark indicator of apoptosis. Our results indicate that apoptosis was potently inhibited by Q-VD-OPh. In stark contrast, Q-VE-OPh did not inhibit apoptosis at a similar dose but required at least 20 times greater concentration than Q-VD-OPh to have any inhibitory effect. Western blot analysis showed that Q-VE-OPh was similarly less effective at inhibiting the activation of the extrinsic (caspase 8 and intrinsic (caspase 9 initiator caspases. Cell proliferation and viability studies further demonstrate that Q-VE-OPh is non-toxic, even at high concentration. Our data indicate that the specificity, effectiveness, and absence of toxicity of Q-VE-OPh provides the appropriate and superior negative control for in vitro and in vivo studies when analyzing the effects of o-phenoxy caspase inhibitors.

  12. A New Orbit for the Eclipsing Binary V577 Oph

    Science.gov (United States)

    Jeffery, Elizabeth J.; Barnes, Thomas G., III; Skillen, Ian; Montemayor, Thomas J.

    2017-09-01

    Pulsating stars in eclipsing binary systems are unique objects for providing constraints on stellar models. To fully leverage the information available from the binary system, full orbital radial velocity curves must be obtained. We report 23 radial velocities for components of the eclipsing binary V577 Oph, whose primary star is a δ Sct variable. The velocities cover a nearly complete orbit and a time base of 20 years. We computed orbital elements for the binary and compared them to the ephemeris computed by Creevey et al. The comparison shows marginally different results. In particular, a change in the systemic velocity by -2 km s-1 is suggested by our results. We compare this systemic velocity difference to that expected due to reflex motion of the binary in response to the third body in the system. The systemic velocity difference is consistent with reflex motion, given our mass determination for the eclipsing binary and the orbital parameters determined by Volkov & Volkova for the three-body orbit. We see no evidence for the third body in our spectra, but we do see strong interstellar Na D lines that are consistent in strength with the direction and expected distance of V577 Oph.

  13. A New Orbit for the Eclipsing Binary V577 Oph

    Energy Technology Data Exchange (ETDEWEB)

    Jeffery, Elizabeth J. [Physics Department, California Polytechnic State University, San Luis Obispo, CA 93407 (United States); Barnes, Thomas G. III; Montemayor, Thomas J. [The University of Texas at Austin, McDonald Observatory, 1 University Station, C1402, Austin, TX 78712-0259 (United States); Skillen, Ian, E-mail: ejjeffer@calpoly.edu, E-mail: tgb@astro.as.utexas.edu, E-mail: tm@astro.as.utexas.edu, E-mail: wji@ing.iac.es [Isaac Newton Group, Apartado de Correos 321, E-38700 Santa Cruz de La Palma, Canary Islands (Spain)

    2017-09-01

    Pulsating stars in eclipsing binary systems are unique objects for providing constraints on stellar models. To fully leverage the information available from the binary system, full orbital radial velocity curves must be obtained. We report 23 radial velocities for components of the eclipsing binary V577 Oph, whose primary star is a δ Sct variable. The velocities cover a nearly complete orbit and a time base of 20 years. We computed orbital elements for the binary and compared them to the ephemeris computed by Creevey et al. The comparison shows marginally different results. In particular, a change in the systemic velocity by −2 km s{sup −1} is suggested by our results. We compare this systemic velocity difference to that expected due to reflex motion of the binary in response to the third body in the system. The systemic velocity difference is consistent with reflex motion, given our mass determination for the eclipsing binary and the orbital parameters determined by Volkov and Volkova for the three-body orbit. We see no evidence for the third body in our spectra, but we do see strong interstellar Na D lines that are consistent in strength with the direction and expected distance of V577 Oph.

  14. Dust formation in Nova Oph 2017 (TCP J17394608-2457555)

    Science.gov (United States)

    Joshi, Vishal; Banerjee, D. P. K.; Srivastava, Mudit

    2017-06-01

    Ongoing NIR observations of Nova Oph 2017 indicate the possible onset of dust formation in Nova Oph 2017. Monitoring in the JHKs bands shows a steady rise in the J-K color from around 1.4 on 5 June 2017 to 2.0 on 13 June 2017.

  15. Comment on Extracting alpha from B to rho rho

    Energy Technology Data Exchange (ETDEWEB)

    Falk, A

    2003-10-29

    Recent experimental results on B {yields} {rho}{rho} decays indicate that the CP asymmetry S{sub {rho}{sup +}{rho}{sup -}} will give an interesting determination of {alpha} = arg[-(V{sub td}V*{sub tb})/(V{sub ud}V*{sub ub})]. In the limit when the {rho} width is neglected, the B {yields} {pi}{pi} isospin analysis can also be applied to B {yields} {rho}{rho}, once an angular analysis is used to separate transversity modes. The present bound on the shift of S{sub {rho}{sup +}{rho}{sup -}} from the true sin 2{alpha} is already stronger than it is for S{sub {pi}{sup +}{pi}{sup -}}. The authors point out a subtle violation of the isospin relations when the two {rho} mesons are observed with different invariant masses, and how to constrain this effect experimentally.

  16. MID-INFRARED SPECTROSCOPIC OBSERVATIONS OF THE DUST-FORMING CLASSICAL NOVA V2676 OPH

    Energy Technology Data Exchange (ETDEWEB)

    Kawakita, Hideyo; Arai, Akira; Shinnaka, Yoshiharu [Koyama Astronomical Observatory, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, Kyoto 603-8555 (Japan); Ootsubo, Takafumi [Department of Earth Science and Astronomy, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902 (Japan); Nagashima, Masayoshi, E-mail: kawakthd@cc.kyoto-su.ac.jp [Department of Physics, Faculty of Science, Kyoto Sangyo University, Motoyama, Kamigamo, Kita-ku, Kyoto 603-8555 (Japan)

    2017-02-01

    The dust-forming nova V2676 Oph is unique in that it was the first nova to provide evidence of C{sub 2} and CN molecules during its near-maximum phase and evidence of CO molecules during its early decline phase. Observations of this nova have revealed the slow evolution of its lightcurves and have also shown low isotopic ratios of carbon ({sup 12}C/{sup 13}C) and nitrogen ({sup 14}N/{sup 15}N) in its envelope. These behaviors indicate that the white dwarf (WD) star hosting V2676 Oph is a CO-rich WD rather than an ONe-rich WD (typically larger in mass than the former). We performed mid-infrared spectroscopic and photometric observations of V2676 Oph in 2013 and 2014 (respectively 452 and 782 days after its discovery). No significant [Ne ii] emission at 12.8 μ m was detected at either epoch. These provided evidence for a CO-rich WD star hosting V2676 Oph. Both carbon-rich and oxygen-rich grains were detected in addition to an unidentified infrared feature at 11.4 μ m originating from polycyclic aromatic hydrocarbon molecules or hydrogenated amorphous carbon grains in the envelope of V2676 Oph.

  17. 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

  18. The Rho Kappa Spirit

    Science.gov (United States)

    McCullagh, Mary T.

    2012-01-01

    Many years ago, Christopher Columbus High School opened a chapter of Rho Kappa, the Social Studies Honor Society developed through the Florida Council for the Social Studies (FCSS). As department chair and member of FCSS, the author was thrilled to be able to offer their students opportunities in the Honor Society for the Social Studies. They…

  19. 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.

  20. Optical and near-IR spectroscopy of nova Oph 2017 (TCP J17394608-2457555)

    Science.gov (United States)

    Raj, Ashish; Pavana, M.; Anupama, G. C.; Bhowmick, Anirban; Dar, Rahul; Kumar, S. Pramod

    2017-05-01

    We report optical and near-IR spectroscopic observations of the nova Oph 2017 (ATel #10366, #10367, #10369). The optical spectrum on May 11, 2017 was obtained using the HFOSC instrument mounted on the 2m Himalayan Chandra Telescope (HCT) of the Indian Astronomical Observatory, Hanle, India, in the 380-800nm wavelength range.

  1. Observations of interstellar C2 toward Chi Oph, HD 154368, 147889 and 149404

    NARCIS (Netherlands)

    Dishoeck, van E.F.; Zeeuw, de P.T.

    1984-01-01

    Interstellar absorption lines of the C2 (2-0) Phillips band at 8750 A have been searched for in the spectra of southern stars. Seventeen lines originating from the lowest eight rotational levels have been detected toward Chi Oph, and eleven lines originating from the lowest five rotational levels

  2. Far-infrared observations of young clusters embedded in the R Coronae Australis and Rho Ophiuchi dark clouds

    Science.gov (United States)

    Wilking, B. A.; Harvey, P. M.; Joy, M.; Hyland, A. R.; Jones, T. J.

    1985-01-01

    Multicolor far-infrared maps in two nearby dark clouds, R Coronae Australis and Rho Ophiuchi, have been made in order to investigate the individual contribution of low-mass stars to the energetics and dynamics of the surrounding gas and dust. Emission from cool dust associated with five low-mass stars has been detected in CrA and four in Rho Oph; their far-infrared luminosities range from 2 solar luminosities to 40 solar luminosities. When an estimate of the bolometric luminosity was possible, it was found that typically more than 50 percent of the star's energy was radiated longward of 20 microns. Meaningful limits to the far-infrared luminosities of an additional 11 association members in CrA and two in Rho Oph were also obtained. The dust optical depth surrounding the star R CrA appears to be asymmetric and may control the dynamics of the surrounding molecular gas. The implications of these results for the cloud energetics and star formation efficiency in these two clouds are discussed.

  3. Far-infrared observations of young clusters embedded in the R Coronae Austrinae and RHO Ophiuchi dark clouds

    Science.gov (United States)

    Wilking, B. A.; Harvey, P. M.; Joy, M.; Hyland, A. R.; Jones, T. J.

    1985-01-01

    Multicolor far infrared maps in two nearby dark clouds, R Coronae Austrinae and rho Ophiuchi, were made in order to investigate the individual contribution of low mass stars to the energetics and dynamics of the surrounding gas and dust. Emission from cool dust associated with five low mass stars in Cr A and four in rho Oph was detected; their far infrared luminosities range from 2 far infrared luminosities L. up to 40 far infrared luminosities. When an estimate of the bolometric luminosity was possible, it was found that typically more than 50% of the star's energy was radiated longward of 20 micrometers. meaningful limits to the far infrared luminosities of an additional eleven association members in Cr A and two in rho Oph were also obtained. The dust optical depth surrounding the star R Cr A appears to be asymmetric and may control the dynamics of the surrounding molecular gas. The implications of the results for the cloud energetics and star formation efficiency in these two clouds are discussed.

  4. RhoA/Rho kinase in spinal cord injury

    Directory of Open Access Journals (Sweden)

    Xiangbing Wu

    2016-01-01

    Full Text Available A spinal cord injury refers to an injury to the spinal cord that is caused by a trauma instead of diseases. Spinal cord injury includes a primary mechanical injury and a much more complex secondary injury process involving inflammation, oxidation, excitotoxicity, and cell death. During the secondary injury, many signal pathways are activated and play important roles in mediating the pathogenesis of spinal cord injury. Among them, the RhoA/Rho kinase pathway plays a particular role in mediating spinal degeneration and regeneration. In this review, we will discuss the role and mechanism of RhoA/Rho kinase-mediated spinal cord pathogenesis, as well as the potential of targeting RhoA/Rho kinase as a strategy for promoting both neuroprotection and axonal regeneration.

  5. V2487 Oph 1998: a post nova in an intermediate polar

    Directory of Open Access Journals (Sweden)

    Hernanz Margarita

    2014-01-01

    Full Text Available V2487 Oph (Nova Oph 1998 is a classical nova that exploded in 1998. XMM-Newton observations performed between 2 and 9 years after the explosion showed emission related to restablished accretion, and indicative of a magnetic white dwarf. The spectrum looks like that of a cataclysmic variable of the intermediate polar type. Anyway, we don’t have yet a definitive confirmation of the intermediate polar character, through determination of spin and orbital periods. Although it is not the first nova exploding in a magnetic white dwarf, it is always challenging to reach explosive conditions when a standard accretion disk can’t be formed, because of the magnetic field. In addition, V2487 Oph has been the first nova where a detection of X-rays - in the host binary system – has been reported prior to its eruption, in 1990 with the ROSAT satellite. V2487 Oph has been also detected in hard X-rays with INTEGRAL/IBIS and RXTE/PCA. Last but not least, V2487 Oph has been identified as a recurrent nova in 2008, since a prior eruption in 1900 has been reported through analysis of Harvard photographic plates. Therefore, it is expected to host a massive white dwarf and be a candidate for a type Ia supernova explosion. In a recent study of the progenitors of galactic novae, it has been emphasized that V2487 Oph is an important and interesting object, "intermediate" between the "standard" classical novae and other historical and well-known recurrent novae with shorter recurrence periods. It could be that in the end there’s a continuous distribution of recurrence periods, instead of the common understanding up to now that "classical" and "recurrent" novae were quite apart (with recurrence periods of more than 104 years and less than 100years - approximately - respectively. We present the results of our campaign of several observations with XMM-Newton. The consequences for the understanding of such a puzzling object are discussed.

  6. Rho GTPase function in tumorigenesis

    DEFF Research Database (Denmark)

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

    2009-01-01

    Malignant tumor cells display uncontrolled proliferation, loss of epithelial cell polarity, altered interactions with neighboring cells and the surrounding extracellular matrix, and enhanced migratory properties. Proteins of the Rho GTPase family regulate all these processes in cell culture and, ...... 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......., 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...

  7. 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......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 difficult to predict. Macrophages isolated from myeloid-restricted RhoA/RhoB (conditional) double knockout (dKO) mice did not express RhoC and were essentially pan-Rho deficient. Using real-time chemotaxis assays, we found that retraction of the trailing edge was dissociated from advance of the cell body...... branches due to impaired lamellipodial retraction. A mouse model of peritonitis indicated that monocyte/macrophage recruitment was, surprisingly, more rapid in RhoA/RhoB dKO mice than in WT mice. In comparison to dKO cells, the phenotypes of single RhoA or RhoB deficient macrophages were mild due to mutual...

  8. Rho signaling participates in membrane fluidity homeostasis.

    Directory of Open Access Journals (Sweden)

    Daniel Lockshon

    Full Text Available Preservation of both the integrity and fluidity of biological membranes is a critical cellular homeostatic function. Signaling pathways that govern lipid bilayer fluidity have long been known in bacteria, yet no such pathways have been identified in eukaryotes. Here we identify mutants of the yeast Saccharomyces cerevisiae whose growth is differentially influenced by its two principal unsaturated fatty acids, oleic and palmitoleic acid. Strains deficient in the core components of the cell wall integrity (CWI pathway, a MAP kinase pathway dependent on both Pkc1 (yeast's sole protein kinase C and Rho1 (the yeast RhoA-like small GTPase, were among those inhibited by palmitoleate yet stimulated by oleate. A single GEF (Tus1 and a single GAP (Sac7 of Rho1 were also identified, neither of which participate in the CWI pathway. In contrast, key components of the CWI pathway, such as Rom2, Bem2 and Rlm1, failed to influence fatty acid sensitivity. The differential influence of palmitoleate and oleate on growth of key mutants correlated with changes in membrane fluidity measured by fluorescence anisotropy of TMA-DPH, a plasma membrane-bound dye. This work provides the first evidence for the existence of a signaling pathway that enables eukaryotic cells to control membrane fluidity, a requirement for division, differentiation and environmental adaptation.

  9. Paving the Rho in cancer metastasis: Rho GTPases and beyond.

    Science.gov (United States)

    Jansen, Sepp; Gosens, Reinoud; Wieland, Thomas; Schmidt, Martina

    2018-03-01

    Malignant carcinomas are often characterized by metastasis, the movement of carcinoma cells from a primary site to colonize distant organs. For metastasis to occur, carcinoma cells first must adopt a pro-migratory phenotype and move through the surrounding stroma towards a blood or lymphatic vessel. Currently, there are very limited possibilities to target these processes therapeutically. The family of Rho GTPases is an ubiquitously expressed division of GTP-binding proteins involved in the regulation of cytoskeletal dynamics and intracellular signaling. The best characterized members of the Rho family GTPases are RhoA, Rac1 and Cdc42. Abnormalities in Rho GTPase function have major consequences for cancer progression. Rho GTPase activation is driven by cell surface receptors that activate GTP exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this review, we summarize our current knowledge on Rho GTPase function in the regulation of metastasis. We will focus on key discoveries in the regulation of epithelial-mesenchymal-transition (EMT), cell-cell junctions, formation of membrane protrusions, plasticity of cell migration and adaptation to a hypoxic environment. In addition, we will emphasize on crosstalk between Rho GTPase family members and other important oncogenic pathways, such as cyclic AMP-mediated signaling, canonical Wnt/β-catenin, Yes-associated protein (YAP) and hypoxia inducible factor 1α (Hif1α) and provide an overview of the advancements and challenges in developing pharmacological tools to target Rho GTPase and the aforementioned crosstalk in the context of cancer therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Antioxidants as stabilizers for His6-OPH: is this an unusual or regular role for them with enzymes?

    Science.gov (United States)

    Efremenko, Elena N; Lyagin, Ilya V; Cuong, Le H; Huong, Le M

    2017-11-01

    The effect of 14 different antioxidants on the activity of a hexahistidine-tagged organophosphorus hydrolase (His6-OPH) has been studied in vitro. It has been found that antioxidants can have a positive, neutral or negative effect on the activity of His6-OPH in a native form or in the form of an enzyme-polyelectrolyte complex, while the enzyme itself does not affect their antioxidant activity. A significant stabilizing effect of a number of antioxidants on His6-OPH has been shown against its inhibiting with organic solvents (DMSO and isopropyl alcohol). The kinetics of the process has been studied. Based on molecular docking of all tested antioxidants to the surface of His6-OPH dimer, options of their localization have been identified. These data were used to explain the revealed stabilizing effect of the antioxidants on the enzyme as well as their negative influence on His6-OPH activity. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  11. 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.

  12. Markus Ophälders, Filosofia Arte Estetica. Incontri e conflitti

    OpenAIRE

    Camparsi, Andrea

    2017-01-01

    Markus Ophälders presenta un breve ma altrettanto denso lavoro che intende dimostrare come l’estetica non sia una semplice branca della ricerca filosofica, nata nel Settecento e sviluppatasi nei secoli a venire, bensì come lo studio filosofico estetico sia una costante che accompagna la storia della filosofia nella sua interezza. Sebbene l’autore non voglia presentare una minuziosa storia dell’estetica, i tre capitoli di cui è composto il testo si impegnano a porre in rilievo i concetti fonda...

  13. Nova Oph 2017 (TCP J17394608-2457555) detected at millimeter wavelengths

    Science.gov (United States)

    Kaminski, T.; Gehrz, R.

    2017-06-01

    Millimeter-wave continuum emission was detected in Nova Oph 2017 (ATel #10366, #10367) with the Submillimeter Array in Hawaii. The object was observed on July 20, 2017 in four spectral ranges: 224.3-232.3, 240.6-248.6, 336-344, and 352-360 GHz. The combined continuum flux in the two lower ranges (i.e., at a wavelength of 1.3 mm) is of 4.8 mJy, well above the noise with an rms of 0.6 mJy per beam.

  14. Rho A and the Rho kinase pathway regulate fibroblast contraction: Enhanced contraction in constitutively active Rho A fibroblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Nobe, Koji, E-mail: kojinobe@pharm.showa-u.ac.jp [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan); Nobe, Hiromi [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan); Department of Physical Therapy, Bunkyo-Gakuin University (Japan); Yoshida, Hiroko [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan); Kolodney, Michael S. [Dermatology Division, Department of Medicine, UCLA, Los Angeles, CA (United States); Paul, Richard J. [Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Honda, Kazuo [Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo (Japan)

    2010-08-20

    Research highlights: {yields} Mechanisms of fibroblast cell contraction in collagen matrix. {yields} Assessed an isometric force development using 3D-reconstituted-fibroblast fiber. {yields} Constitutively active Rho A induced the over-contraction of fibroblast cells. {yields} Rho A and Rho kinase pathway has a central role in fibroblast cell contraction. -- Abstract: Fibroblast cells play a central role in the proliferation phase of wound healing processes, contributing to force development. The intracellular signaling pathways regulating this non-muscle contraction are only partially understood. To study the relations between Rho A and contractile responses, constitutively active Rho A (CA-Rho A) fibroblast cells were reconstituted into fibers and the effects of calf serum (CS) on isometric force were studied. CS-induced force in CA-Rho A fibroblast fibers was twice as large as that in wild type (NIH 3T3) fibroblast fibers. During this response, the translocation of Rho A from the cytosol to the membrane was detected by Rho A activity assays and Western blot analysis. Pre-treatment with a Rho specific inhibitor (C3-exoenzyme) suppressed translocation as well as contraction. These results indicate that Rho A activation is essential for fibroblast contraction. The Rho kinase inhibitor ( (Y27632)) inhibited both NIH 3T3 and CA-Rho A fibroblast fiber contractions. Activation of Rho A is thus directly coupled with Rho kinase activity. We conclude that the translocation of Rho A from the cytosol to the membrane and the Rho kinase pathway can regulate wound healing processes mediated by fibroblast contraction.

  15. Period changes of cataclysmic variables below the period gap: V2051 Oph, OY Car and Z Cha

    Science.gov (United States)

    Pilarčík, L.; Wolf, M.; Zasche, P.; Vraštil, J.

    2018-04-01

    We present our results of a long-term monitoring of cataclysmic variable stars (CVs). About 40 new eclipses were measured for the three southern SU UMa-type eclipsing CVs: V2051 Oph, OY Car and Z Cha. Based on the current O - C diagrams we confirmed earlier findings that V2051 Oph and OY Car present cyclic changes of their orbital periods lasting 25 and 29 years, respectively. In case of Z Cha we propose the light-time effect caused probably by a presence of the third component orbiting the eclipsing CV with the period of 43.5 years. The minimal mass of this companion results about 15 MJup.

  16. Hunting for the alpha: $B\\to \\rho\\rho$, $B \\to \\pi\\pi$, $B \\to\\pi\\rho$

    OpenAIRE

    Ovanesyan, G. G.; Vysotsky, M. I.

    2005-01-01

    The hypothesis of the smallness of penguin contribution to charmless strangeless $B_d (\\bar B_d)$ decays allows to determine with high accuracy the value of angle $\\alpha$ from the currently available $B \\to \\rho\\rho$, $B \\to \\pi\\pi$ and $B\\to \\rho\\pi$ decay data.

  17. CORE

    DEFF Research Database (Denmark)

    Krigslund, Jeppe; Hansen, Jonas; Hundebøll, Martin

    2013-01-01

    State-of-the-art in network coding for wireless, meshed networks typically considers two problems separately. First, the problem of providing reliability for a single session. Second, the problem of opportunistic combination of flows by using minimalistic coding, i.e., by XORing packets from...... different flows. Instead of maintaining these approaches separate, we propose a protocol (CORE) that brings together these coding mechanisms. Our protocol uses random linear network coding (RLNC) for intra- session coding but allows nodes in the network to setup inter- session coding regions where flows...

  18. Identification and isolation of bacteria containing OPH enzyme for biodegradation of organophosphorus pesticide diazinon from contaminated agricultural soil

    Directory of Open Access Journals (Sweden)

    Sara Mobarakpoor

    2015-04-01

    Full Text Available Background: Organophosphorus insecticide diazinon has been widely used in agriculture and has the ability to transfer and accumulate in soil, water and animal tissues, and to induce toxicity in plants, animals and humans. In humans, diazinon inhibits nerve transmission by inactivating acetylcholinesterase enzyme. The present study was carried out to identify bacteria containing OPH enzyme for biodegradation of diazinon from contaminated agricultural soil. Methods: In this study, 8 contaminated agricultural soil samples that were exposed to pesticides, especially diazinon in the last two decades, were collected from the farms of Hamedan province. After preparing the media, for isolation of several bacterial strains containing OPH enzyme that are capable of biodegrading organophosphorus pesticides by diazinon enzymatic hydrolysis, bacterial genomic DNA extraction, plasmid product sequencing, phylogenetic sequence processing and phylogenetic tree drawing were carried out. Results: Eight bacterial strains, capable of secreting OPH enzyme, were isolated from soil samples, one of which named BS-1 with 86% similarity to Bacillus safensis displayed the highest organophosphate-hydrolyzing capability and can be used as a source of carbon and phosphorus. Conclusion: It can be concluded that the isolated bacterial strain identified in this study with OPH enzyme secretion has the potential for biodegradation of organophosphorus pesticides, especially diazinon in invitro conditions. Also, further studies such as the environmental stability and interaction, production strategies, safety, cost-benefit, environmental destructive parameters, and, toxicological, genetic and biochemical aspects are recommended prior to the application of bacterial strains in the field-scale bioremediation.

  19. Optical and Near-infrared Study of Nova V2676 Oph 2012

    Energy Technology Data Exchange (ETDEWEB)

    Raj, A. [Korea Astronomy and Space Science Institute, Daejeon, 34055 (Korea, Republic of); Das, R. K. [Department of Astrophysics and Cosmology, S N Bose National Centre for Basic Sciences, Salt Lake, Kolkata 700106 (India); Walter, F. M., E-mail: ashish.raj@iiap.res.in [Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794-3800 (United States)

    2017-02-01

    We present optical spectrophotometric and near-infrared (NIR) photometric observations of the nova V2676 Oph covering the period from 2012 March 29 through 2015 May 8. The optical spectra and photometry of the nova have been taken from SMARTS and Asiago; the NIR photometry was obtained from SMARTS and Mt. Abu. The spectra were dominated by strong H i lines from the Balmer series, Fe ii, N i, and [O i] lines in the initial days, typical of an Fe ii type nova. The measured FWHM for the H β and H α lines was 800–1200 km s{sup −1}. There was pronounced dust formation starting 90 days after the outburst. The J − K color was the largest among recent dust-forming novae.

  20. 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.

  1. {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)

  2. 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.

  3. 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.

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

    DEFF Research Database (Denmark)

    Dovas, Athanassios; Couchman, John R

    2005-01-01

    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...... and the importance of the particular membrane microenvironment that represents the site of action for GTPases. All these results point to a wider role for RhoGDI than initially perceived, making it a binding partner that can tightly control Rho GTPases, but which also allows them to reach their full spectrum......RhoGDI (Rho GDP-dissociation inhibitor) was identified as a down-regulator of Rho family GTPases typified by its ability to prevent nucleotide exchange and membrane association. Structural studies on GTPase-RhoGDI complexes, in combination with biochemical and cell biological results, have provided...

  5. RhoB: Team Oncogene or Team Tumor Suppressor?

    Science.gov (United States)

    Ju, Julia A; Gilkes, Daniele M

    2018-01-30

    Although Rho GTPases RhoA, RhoB, and RhoC share more than 85% amino acid sequence identity, they play very distinct roles in tumor progression. RhoA and RhoC have been suggested in many studies to contribute positively to tumor development, but the role of RhoB in cancer remains elusive. RhoB contains a unique C-terminal region that undergoes specific post-translational modifications affecting its localization and function. In contrast to RhoA and RhoC, RhoB not only localizes at the plasma membrane, but also on endosomes, multivesicular bodies and has even been identified in the nucleus. These unique features are what contribute to the diversity and potentially opposing functions of RhoB in the tumor microenvironment. Here, we discuss the dualistic role that RhoB plays as both an oncogene and tumor suppressor in the context of cancer development and progression.

  6. 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).

  7. Pathophysiological effects of RhoA and Rho-associated kinase on cardiovascular system.

    Science.gov (United States)

    Cai, Anping; Li, Liwen; Zhou, Yingling

    2016-01-01

    In past decades, growing evidence from basic and clinical researches reveal that small guanosine triphosphate binding protein ras homolog gene family, member A (RhoA) and its main effector Rho-associated kinase (ROCK) play central and complex roles in cardiovascular systems, and increasing RhoA and ROCK activity is associated with a broad range of cardiovascular diseases such as congestive heart failure, atherosclerosis, and hypertension. Favorable outcomes have been observed with ROCK inhibitors treatment. In this review, we briefly summarize the pathophysiological roles of RhoA/ROCK signaling pathway on cardiovascular system, displaying the potential benefits in the cardiovascular system with controlling RhoA/ROCK signaling pathway.

  8. Survival of corticostriatal neurons by Rho/Rho-kinase signaling pathway.

    Science.gov (United States)

    Kobayashi, Kenta; Sano, Hiromi; Kato, Shigeki; Kuroda, Keisuke; Nakamuta, Shinichi; Isa, Tadashi; Nambu, Atsushi; Kaibuchi, Kozo; Kobayashi, Kazuto

    2016-09-06

    Developing cortical neurons undergo a number of sequential developmental events including neuronal survival/apoptosis, and the molecular mechanism underlying each characteristic process has been studied in detail. However, the survival pathway of cortical neurons at mature stages remains largely uninvestigated. We herein focused on mature corticostriatal neurons because of their important roles in various higher brain functions and the spectrum of neurological and neuropsychiatric disorders. The small GTPase Rho is known to control diverse and essential cellular functions through some effector molecules, including Rho-kinase, during neural development. In the present study, we investigated the role of Rho signaling through Rho-kinase in the survival of corticostriatal neurons. We performed the conditional expression of Clostridium botulinum C3 ADP-ribosyltransferase (C3 transferase) or dominant-negative form for Rho-kinase (Rho-K DN), a well-known inhibitor of Rho or Rho-kinase, respectively, in corticostriatal neurons using a dual viral vector approach combining a neuron-specific retrograde gene transfer lentiviral vector and an adeno-associated virus vector. C3 transferase markedly decreased the number of corticostriatal neurons, which was attributed to caspase-3-dependent enhanced apoptosis. In addition, Rho-K DN produced phenotypic defects similar to those caused by C3 transferase. These results indicate that the Rho/Rho-kinase signaling pathway plays a crucial role in the survival of corticostriatal neurons. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Rho GTPases: masters of cell migration.

    Science.gov (United States)

    Sadok, Amine; Marshall, Chris J

    2014-01-01

    Since their discovery in the late eighties, the role of Rho GTPases in the regulation of cell migration has been extensively studied and has mainly focused on the hallmark family members Rho, Rac, and Cdc42. Recent technological advances in cell biology, such as Rho-family GTPase activity biosensors, studies in 3D, and unbiased RNAi-based screens, have revealed an increasingly complex role for Rho GTPases during cell migration, with many inter-connected functions and a strong dependency on the physical and chemical properties of the surrounding environment. This review aims to give an overview of recent studies on the role of Rho-family GTPase members in the modulation of cell migration in different environments, and discuss future directions.

  10. Searching for T dwarfs in the ρ Oph dark cloud L 1688

    Science.gov (United States)

    Chiang, Poshih; Chen, Wen-Ping; Albert, Loïc; Liu, Michael; Magnier, Eugene A.

    2015-03-01

    We present a list of T dwarf candidates in the dark cloud L 1688 in the ρ Oph star-forming region. These candidates are selected with infrared colours sensitive to T dwarf characteristics of methane absorptions and of cool atmospheres. The 1.6-μm methane feature is diagnosed by on-off imaging using an H-band and an intermediate-band methane filter, calibrated to a set of known brown dwarfs of M, L, and T types in the field. Another methane feature at 3.3 μm is traced with the Spitzer/Infrared Array Camera (IRAC) [3.6] - [4.5] colour. For cool atmospheres, the H - [4.5] and K - [4.5] colours are utilized. With an additional criterion of mid-infrared brightness to eliminate extragalactic interlopers, a total of 28 T dwarf candidates have been identified. A comprehensive assessment was conducted to estimate the level of contamination of our sample by young stellar variability, by extragalactic sources sharing the same colour behaviour, or by foreground T dwarfs. Though extragalactic sources may contribute up to about half of the false positives, our candidates show close spatial association with the dark cloud, rather than randomly distributed as a background population would have been. Furthermore, even though our candidates are not selected a priori by a colour-magnitude relation, they mostly follow the 1 Myr isochrones, ascertaining their youth. Our selection methodology provides guidance to search for T dwarfs in other star-forming regions. Our candidate list, when comparing with those in the literature, which often rely on a single criterion on cool temperature or methane, is more conservative but should be more secure for follow-up spectroscopic confirmation of a T dwarf sample at the early evolutionary stage.

  11. Optimization of the Use of His6-OPH-Based Enzymatic Biocatalysts for the Destruction of Chlorpyrifos in Soil

    Directory of Open Access Journals (Sweden)

    Olga Senko

    2017-11-01

    Full Text Available Applying enzymatic biocatalysts based on hexahistidine-containing organophosphorus hydrolase (His6-OPH is suggested for the decomposition of chlorpyrifos, which is actively used in agriculture in many countries. The application conditions were optimized and the following techniques was suggested to ensure the highest efficiency of the enzyme: first, the soil is alkalinized with hydrated calcitic lime Ca(OH2, then the enzyme is introduced into the soil at a concentration of 1000 U/kg soil. Non-equilibrium low temperature plasma (NELTP-modified zeolite is used for immobilization of the relatively inexpensive polyelectrolyte complexes containing the enzyme His6-OPH and a polyanionic polymer: poly-l-glutamic acid (PLE50 or poly-l-aspartic acid (PLD50. The soil’s humidity is then increased up to 60–80%, the top layer (10–30 cm of soil is thoroughly stirred, and then exposed for 48–72 h. The suggested approach ensures 100% destruction of the pesticide within 72 h in soils containing as much as 100 mg/kg of chlorpyrifos. It was concluded that using this type of His6-OPH-based enzyme chemical can be the best approach for soils with relatively low humus concentrations, such as sandy and loam-sandy chestnut soils, as well as types of soil with increased alkalinity (pH 8.0–8.4. Such soils are often encountered in desert, desert-steppe, foothills, and subtropical regions where chlorpyrifos is actively used.

  12. RhoA of the Rho family small GTPases is essential for B lymphocyte development.

    Directory of Open Access Journals (Sweden)

    Shuangmin Zhang

    Full Text Available RhoA is a member of the Rho family small GTPases that are implicated in various cell functions including proliferation and survival. However, the physiological role of RhoA in vivo remains largely unknown. Here, we deleted RhoA in the B cell and hematopoietic stem cell (HSC populations in RhoA(flox/flox mice with CD19 and Mx promoter-driven Cre expression, respectively. Deletion of RhoA by CD19(Cre/+ significantly blocked B cell development in spleen, leading to a marked reduction in the number of transitional, marginal zone, and follicular B cells. Surprisingly, neither B cell proliferation in response to either LPS or B cell receptor (BCR engagement nor B cell survival rate in vivo was affected by RhoA deletion. Furthermore, RhoA(-/- B cells, like control cells, were rescued from apoptosis by BCR crosslinking in vitro. In contrast, RhoA deficiency led to a defect in B cell activating factor (BAFF-mediated B cell survival that was associated with a dampened expression of BAFF receptor and a loss of BAFF-mediated Akt activation. Finally, HSC deletion of RhoA by Mx-Cre severely reduced proB/preB and immature B cell populations in bone marrow while common lymphoid progenitors were increased, indicating that RhoA is also required for B cell progenitor/precursor differentiation. Taken together, our results uncover an important role for RhoA at multiple stages of B cell development.

  13. 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...

  14. Search for the Decay B{sup 0} --> {rho}{sup 0} {rho}{sup 0}

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B

    2004-08-16

    The B{sup 0} --> {rho}{sup 0}{rho}{sup 0} decay mode is searched for in a data sample of about 227 million {Upsilon}(4S) --> B{bar B} decays collected with the BABAR detector at the PEP-II asymmetric B factory at SLAC. No significant signal is observed, and an upper limit of 1.1x10{sup -6} (90% C.L.) on the branching fraction is set. Implications on the penguin contribution and constraints on the CKM angle {alpha} with B --> {rho}{rho} decays are discussed. All results are preliminary.

  15. rho /sup 0/ rho /sup 0/ pi /sup 0/ in the T region

    CERN Document Server

    Chapman, J; Honma, A; Roe, B P

    1974-01-01

    In view of recent negative results obtained by workers investing the rho /sup 0/ rho /sup 0/ pi /sup 0/ enhancement in the T-meson region in pn annihilations, the authors report a re-analysis of the original BNL data used by Kalbfleisch et al. (1969). The maximum likelihood analysis technique used on all other data has been used on the BNL data, and it is concluded the no significant rho /sup 0/ rho /sup 0/ pi /sup 0/ resonance structure is indicated. (4 refs).

  16. ELP-OPH/BSA/TiO2 nanofibers/c-MWCNTs based biosensor for sensitive and selective determination of p-nitrophenyl substituted organophosphate pesticides in aqueous system.

    Science.gov (United States)

    Bao, Jing; Hou, Changjun; Dong, Qiuchen; Ma, Xiaoyu; Chen, Jun; Huo, Danqun; Yang, Mei; Galil, Khaled Hussein Abd El; Chen, Wilfred; Lei, Yu

    2016-11-15

    A novel biosensor for rapid, sensitive and selective monitoring of p-nitrophenyl substituted organophosphate pesticides (OPs) in aqueous system was developed using a functional nanocomposite which consists of elastin-like-polypeptide-organophosphate hydrolase (ELP-OPH), bovine serum albumin (BSA), titanium dioxide nanofibers (TiO2NFs) and carboxylic acid functionalized multi-walled carbon nanotubes (c-MWCNTs). ELP-OPH was simply purified from genetically engineered Escherichia coli based on the unique phase transition of ELP and thus served as biocatalyst for OPs, while BSA was used to stabilize OPH activity in the nanocomposite. TiO2NFs was employed to enrich organophosphates in the nanocomposite due to its strong affinity with phosphoric group in OPs, while c-MWCNTs was used to enhance the electron transfer in the amperometric detection as well as for covalent immobilization of ELP-OPH. ELP-OPH/BSA/TiO2NFs/c-MWCNTs nanocomposite were systematically characterized using field emission scanning electron microscopy (SEM), Raman spectra, Fourier Transform infrared spectroscopy (FTIR) and X-ray Diffraction (XRD). Under the optimized operating conditions, the ELP-OPH/BSA/TiO2NFs/c-MWCNTs based biosensor for OPs shows a wide linear range, a fast response (less than 5s) and limits of detection (S/N=3) as low as 12nM and 10nM for methyl parathion and parathion, respectively. Such excellent sensing performance can be attributed to the synergistic effects of the individual components in the nanocomposite. Its further application for selectively monitoring OPs compounds spiked in lake water samples was also demonstrated with good accuracy. These features indicate that the developed nanocomposite offers an excellent biosensing platform for rapid, sensitive and selective detection of organophosphates compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Updated Measurement of the CKM Angle alpha Using B0->rho+rho- Decays

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B

    2006-09-26

    The authors present results from an analysis of B{sup 0} {yields} {rho}{sup +}{rho}{sup -} using 316 fb{sup -1} of {Upsilon}(4S) {yields} B{bar B} decays observed with the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. They measure the B{sup 0} {yields} {rho}{sup +}{rho}{sup -} branching fraction, longitudinal polarization fraction f{sub L}, and the CP-violating parameters S{sub long} and C{sub long}: {Beta}(B{sup 0} {yields} {rho}{sup +}{rho}{sup -}) = (23.5 {+-} 2.2(stat) {+-} 4.1(syst)) x 10{sup -6}, f{sub L} = 0.977 {+-} 0.024(stat){sub -0.013}{sup +0.015}(syst), S{sub long} = -0.19 {+-} 0.21(stat){sub -0.07}{sup +0.05}(syst), C{sub long} = -0.07 {+-} 0.15(stat) {+-} 0.06(syst). Using an isospin analysis of B {yields} {rho}{rho} decays they determine the angle {alpha} of the unitarity triangle. One of the two solutions, {alpha} [74,117]{sup o} at 68% CL, is compatible with the standard model. All results presented here are preliminary.

  18. H/D exchange in the reaction of D2 with Bis(triphenyl phosphite)(acetylacetonato)rhodium(I), Rh(P(OPh)3)2(acac)

    International Nuclear Information System (INIS)

    Whitmore, B.C.; Eisenberg, R.

    1984-01-01

    The reaction of Rh(P)OPh) 3 ) 2 (acac) (1) with D 2 benzene has been studied by 1 H NMR spectroscopy, and complex 1 has been found to undergo H/D exchange at the ortho positions of the coordinated phosphite ligands and at the central methine position of the acetylacetonate ligand. At 75 0 C, the exchange reaction proceeds with the extent of deuterium incorporation into P(OPh) 3 being the same as that into acac at all stages of the H/D exchange process. At 60 0 C, deuterium incorporation into P(OPh) 3 is initially more rapid than that into the acac ligand. The initial rate of deuterium incorporation into P(OPh) 3 by 1 in benzene-d 6 under D 2 at 60 0 C proceeds with a first-order rate constant of 9.6 x 10 -5 s -1 . A mechanism for this exchange process is proposed. 13 references, 3 figures, 2 tables

  19. 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.

  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. RhoB: Team Oncogene or Team Tumor Suppressor?

    Directory of Open Access Journals (Sweden)

    Julia A. Ju

    2018-01-01

    Full Text Available Although Rho GTPases RhoA, RhoB, and RhoC share more than 85% amino acid sequence identity, they play very distinct roles in tumor progression. RhoA and RhoC have been suggested in many studies to contribute positively to tumor development, but the role of RhoB in cancer remains elusive. RhoB contains a unique C-terminal region that undergoes specific post-translational modifications affecting its localization and function. In contrast to RhoA and RhoC, RhoB not only localizes at the plasma membrane, but also on endosomes, multivesicular bodies and has even been identified in the nucleus. These unique features are what contribute to the diversity and potentially opposing functions of RhoB in the tumor microenvironment. Here, we discuss the dualistic role that RhoB plays as both an oncogene and tumor suppressor in the context of cancer development and progression.

  2. 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.

    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.

  3. 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)

  4. Rho GTPases in collective cell migration

    NARCIS (Netherlands)

    Zegers, M.M.; Friedl, P.

    2014-01-01

    The family of Rho GTPases are intracellular signal transducers that link cell surface signals to multiple intracellular responses. They are best known for their role in regulating actin dynamics required for cell migration, but in addition control cell-cell adhesion, polarization, vesicle

  5. Improved Measurement of the CKM Angle alpha Using B0 to rho+rho- Decays.

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.

    2005-03-29

    We present results from an analysis of B{sup 0} ({bar 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. We measure the longitudinal polarization fraction f{sub L} = 0.978 {+-} 0.014(stat){sub -0.029}{sup +0.021}(syst) and the CP-violating parameters 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). Using an isospin analysis of B {yields} {rho}{rho} decays we determine the unitarity triangle {alpha}. The solution compatible with the Standard Model is {alpha} = (100 {+-} 13){sup o}.

  6. Concerning the spectroscopy of heavy rho', rho'' and omega', omega'' resonances

    CERN Document Server

    Achasov, N N

    2002-01-01

    Some topics on the spectroscopy of the isovector rho', rho''- and isoscalar omega', omega'' resonances using the magnitudes of bare masses and coupling constants of the above states found in the fits of the data on the reactions of e sup + e sup - annihilation, tau-lepton decays, and the reactions K sup - p -> pi sup +pi sup -LAMBDA, are discussed. In particular, the branching ratios and full widths are evaluated, and the shift of the visible position of the resonance peaks in the energy dependence of the cross sections on the bare mass is considered. The latter is significant for the wide resonances. The comparison with existing models of the rho', rho'' and omega', omega'' resonances is presented

  7. 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

  8. Immunological and Functional Characterization of RhoGDI3 and Its Molecular Targets RhoG and RhoB in Human Pancreatic Cancerous and Normal Cells.

    Directory of Open Access Journals (Sweden)

    Mercedes Piedad de León-Bautista

    Full Text Available RhoGDI proteins have been implicated in several human cancers; changes in their expression levels have shown pro- or anti-tumorigenic effects. Pancreatic Ductal Adenocarcinoma (PDAC is a complex pathology, with poor prognosis, and most patients die shortly after diagnosis. Efforts have been focused on understanding the role of RhoGDI's in PDAC, specially, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has not been studied in relation to cancer or to PDAC. Here, we characterized the expression and functionality of RhoGDI3 and its target GTPases, RhoG and RhoB in pancreatic cell lines from both normal pancreatic tissue and tissue in late stages of PDAC, and compared them to human biopsies. Through immunofluorescences, pulldown assays and subcellular fractionation, we found a reduction in RhoGDI3 expression in the late stages of PDAC, and this reduction correlates with tumor progression and aggressiveness. Despite the reduction in the expression of RhoGDI3 in PDAC, we found that RhoB was underexpressed while RhoG was overexpressed, suggesting that cancerous cells preserve their capacity to activate this pathway, thus these cells may be more eager to response to the stimuli needed to proliferate and become invasive unlike normal cells. Surprisingly, we found nuclear localization of RhoGDI3 in non-cancerous pancreatic cell line and normal pancreatic tissue biopsies, which could open the possibility of novel nuclear functions for this protein, impacting gene expression regulation and cellular homeostasis.

  9. Rho/rho-kinase signalling in chronically alcohol-fed mice.

    Science.gov (United States)

    Kubat, Havva; Yurtsever, Ahmet Sencer; Büyükafşar, Kansu

    2017-04-18

    The effects of chronic ethanol consumption on male sexual function are debateable, and its effects on the Rho/Rho-kinase pathway are unknown. Therefore, we investigated smooth muscle reactivity and Rho/Rho-kinase signalling in the corpus cavernosum of ethanol-fed mice. Ethanol was added to drinking water at 5% concentration in the first 2 days with 5% increment every subsequent 2 days, up to a final concentration of 20% for 45 days. Corpora cavernosa were isolated and a cumulative dose-response curve to phenylephrine was obtained. Acetylcholine (10-6 M), electrical field stimulation (EFS, 40 V, 8-16 Hz) and Y-27632 (10 -6 -10 -5 M)-induced relaxations were compared in the control and ethanol groups. Blood ethanol levels in the control and ethanol-treated mice were 1.5 ± 0.3 mg/dL and 37.4 ± 4.1 mg/dL (P drinking may increase sensitivity to both vasoconstrictors and vasodilators in the mouse corpus cavernosum without any alteration in Rho/Rho-kinase signalling.

  10. 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.

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

    Science.gov (United States)

    Kaplan, Halil Mahir; Pazarci, Percin

    2017-11-01

    Δ 9 -Tetrahydrocannabinol (Δ 9 -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 Δ 9 -THC treated mice. One group of mice are treated with Δ 9 -THC once to see effects of acute treatment. Another group of mice are treated with Δ 9 -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 Δ 9 -THC decreased the expression of rhoA while acute treatment has no meaningful effect on it. Administration of Δ 9 -THC did not affect expression of rho-kinase on both chronic and acute treatment. Administration of Δ 9 -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 Δ 9 -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. Δ 9 -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 Δ 9 -THC together can be useful on rho-kinase related diseases.

  12. 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.

  13. 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.

  14. Direct CP Violation in Charmed Hadron Decays via $\\rho-\\omega$ Mixing

    OpenAIRE

    Guo, X. -H.; Thomas, A. W.

    1999-01-01

    We study the possibility of obtaining large direct CP violation in the charmed hadron decays $D^+ \\to \\rho^+ \\rho^0 (\\omega) \\to \\rho^+ \\pi^+\\pi^-$, $D^+ \\to \\pi^+ \\rho^0 (\\omega) \\to \\pi^+ \\pi^+\\pi^-$, $D^0 \\to \\phi \\rho^0 (\\omega) \\to\\phi \\pi^+\\pi^-$, $D^0 \\to\\eta \\rho^0 (\\omega) \\to\\eta \\pi^+\\pi^-$, $D^0 \\to \\eta' \\rho^0 (\\omega) \\to\\eta' \\pi^+\\pi^-$, $D^0 \\to \\pi^0 \\rho^0 (\\omega) \\to \\pi^0 \\pi^+\\pi^-$, and $\\Lambda_c \\ra p \\rho^0 (\\omega) \\to p \\pi^+\\pi^-$ via $\\rho-\\omega$ mixing. The a...

  15. 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

  16. 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

  17. 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.

  18. Gαq/p63RhoGEF interaction in RhoA/Rho kinase signaling: investigation in Gitelman's syndrome and implications with hypertension.

    Science.gov (United States)

    Pagnin, E; Ravarotto, V; Maiolino, G; Naso, E; Davis, P A; Calò, L A

    2018-03-01

    Gitelman's syndrome (GS) presents normo-hypotension and absence of cardiovascular-renal remodeling despite high angiotensin II (Ang II), activation of renin-angiotensin-aldosterone system and is a human model of endogenous antagonism of Ang II signaling, opposite to hypertension. GS's clinical presentation leads to questions regarding what features might be responsible. One area of investigation involves Ang II signaling. In hypertensive patients, RhoA/Rho kinase (RhoA/ROCK) pathway activation by Ang II is involved in hypertension development/maintenance and induction of long-term consequences (cardiovascular-renal remodeling), while GS has reduced p63RhoGEF gene and protein levels and ROCK activity. Ang II signaling is mediated by Gαq, which interacts with p63RhoGEF via the α6-αN linker connecting p63RhoGEF's DH and PH domains acting as a conformational switch to activate RhoA/ROCK signaling. We have investigated in GS patients, the presence of mutations in either p63RhoGEF's α6-αN linker domain and in Gαq's Ala253, Trp263, and Tyr356 residues, crucial for p63RhoGEF-Gαq interplay. No mutations have been found in specific aminoacids of p63RhoGEF α6-αN linker and Gαq, key for p63RhoGEF/Gαq interplay. Gitelman's syndrome normo/hypotension and lack of cardiovascular-renal remodeling are not due to mutations of p63RhoGEF α6-αN linker and Gαq interactions. This opens the way for investigations on different coding and no-coding regions (p63RhoGEF and Gαq promoters) and on altered transcriptional/post-transcriptional regulation. Clarification of how these biochemical/molecular mechanisms work/interact would provide insights into mechanisms involved in the GS's Ang II signaling fine tuning, in human physiology/pathophysiology in general and could also identify significant targets for intervention in the treatments of hypertension.

  19. 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.

  20. Observation of the Decay B0->rho+rho- and Measurement of the Branching Fraction and Polarization

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B

    2003-12-02

    We have observed the rare decay B{sup 0} {yields} {rho}{sup +}{rho}{sup -} in a sample of 89 million B{bar B} pairs recorded with the BABAR detector. We measure the branching fraction {Beta}(B{sup 0} {yields} {rho}{sup +}{rho}{sup -}) = (27{sub -6-7}{sup +7+5}) x 10{sup -6} and determine the longitudinal polarization fraction {Lambda}{sub L}/{Lambda} = 0.99{sub -0.07}{sup +0.01} {+-} 0.03. The results are preliminary.

  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. 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.

  3. Determination of the branching ratio tau. -->. rho nu

    Energy Technology Data Exchange (ETDEWEB)

    Becker, J.J.; Blaylock, G.T.; Bolton, T.; Brown, J.S.; Bunnell, K.O.; Burnett, T.H.; Cassell, R.E.; Coffman, D.; Cook, V.; Coward, D.H.

    1987-02-01

    The decay tau ..-->.. rho nu was studied in tau- pair production by e/sup +/e/sup -/ annihilation at ..sqrt..s = 3.77 GeV. The branching ratio was measured to be B(rho nu) = 22.3 +- 1.4 +- 1.6%. 5 refs., 2 figs.

  4. 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.

  5. Hadronic pollution in B $\\to \\rho\\pi$?

    CERN Document Server

    Polosa, Antonio

    2003-01-01

    The B -> 3pi decay via rho has been shown, in two independent calculations, to be very sensible to the B -> sigma pi background. This potentially complicates the extraction of alpha through the isospin analysis of B -> rho pi. I will briefly review this topic.

  6. Roles of rho GTPases in intracellular transport and cellular transformation.

    Science.gov (United States)

    Chi, Xiaojuan; Wang, Song; Huang, Yifan; Stamnes, Mark; Chen, Ji-Long

    2013-03-28

    Rho family GTPases belong to the Ras GTPase superfamily and transduce intracellular signals known to regulate a variety of cellular processes, including cell polarity, morphogenesis, migration, apoptosis, vesicle trafficking, viral transport and cellular transformation. The three best-characterized Rho family members are Cdc42, RhoA and Rac1. Cdc42 regulates endocytosis, the transport between the endoplasmic reticulum and Golgi apparatus, post-Golgi transport and exocytosis. Cdc42 influences trafficking through interaction with Wiskott-Aldrich syndrome protein (N-WASP) and the Arp2/3 complex, leading to changes in actin dynamics. Rac1 mediates endocytic and exocytic vesicle trafficking by interaction with its effectors, PI3kinase, synaptojanin 2, IQGAP1 and phospholipase D1. RhoA participates in the regulation of endocytosis through controlling its downstream target, Rho kinase. Interestingly, these GTPases play important roles at different stages of viral protein and genome transport in infected host cells. Importantly, dysregulation of Cdc42, Rac1 and RhoA leads to numerous disorders, including malignant transformation. In some cases, hyperactivation of Rho GTPases is required for cellular transformation. In this article, we review a number of findings related to Rho GTPase function in intracellular transport and cellular transformation.

  7. RhoA Controls Wnt Upregulation on Microstructured Titanium Surfaces

    Directory of Open Access Journals (Sweden)

    Simone Lumetti

    2014-01-01

    Full Text Available Rough topography enhances the activation of Wnt canonical signaling in vitro, and this mediates its effects on cell differentiation. However, the molecular mechanisms underlying topography-dependent control of Wnt signaling are still poorly understood. As the small GTPase RhoA controls cytoskeletal reorganization and actomyosin-induced tensional forces, we hypothesized that RhoA could affect the activation of Wnt signaling in cells on micropatterned titanium surfaces. G-LISA assay revealed that RhoA activation was higher in C2C12 cells on rough (SLA surfaces under basal conditions than on smooth (Polished titanium. Transfection with dominant negative RhoA decreased Wnt activation by normalized TCF-Luc activity on SLA, whilst transfection with constitutively active RhoA increased TCF-Luc activation on Polished titanium. One mM Myosin II inhibitor Blebbistatin increased RhoA activation but decreased Wnt activation on SLA surfaces, indicating that tension-generating structures are required for canonical Wnt modulation on titanium surfaces. Actin inhibitor Cytochalasin markedly enhanced RhoA and TCF-Luc activation on both surfaces and increased the expression of differentiation markers in murine osteoblastic MC3T3 cells. Taken together, these data show that RhoA is upregulated in cells on rough surfaces and it affects the activation of Wnt canonical signaling through Myosin II modulation.

  8. A Study of B0 to rho+rho- Decays and Constraints on theCKM Angle alpha

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.

    2007-05-16

    The authors present results from an analysis of B{sup 0} {yields} {rho}{sup +}{rho}{sup -} decays using (383.6 {+-} 4.2) x 10{sup 6} B{bar B} pairs collected by the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. The measurements of the B{sup 0} {yields} {rho}{sup +}{rho}{sup -} branching fraction, longitudinal polarization fraction f{sub L}, and the CP-violating parameters S{sub long} and C{sub long} are: {Beta}(B{sup 0} {yields} {rho}{sup +}{rho}{sup -}) = (25.5 {+-} 2.1(stat){sub -3.9}{sup +3.6}(syst)) x 10{sup -6}, f{sub L} = 0.992 {+-} 0.024(stat){sub -0.013}{sup +0.026}(syst), S{sub long} = -0.17 {+-} 0.20(stat){sub -0.06}{sup +0.05}(syst), C{sub long} = 0.01 {+-} 0.15(stat) {+-} 0.06(syst). The authors determine the unitarity triangle angle {alpha}, using an isospin analysis of B {yields} {rho}{rho} decays. One of the two solutions, {alpha} = [73.1, 117.0]{sup o} at 68% CL is compatible with standard model-based fits of existing data. Constraints on the unitarity triangle are also evaluated using an SU(3) symmetry based approach.

  9. Evidence for B(0) --> rho(0)rho(0) decays and implications for the Cabibbo-Kobayashi-Maskawa angle alpha.

    Science.gov (United States)

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Pegna, D Lopes; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I; Pripstein, M; Roe, N A; Ronan, M T; Tackmann, K; Wenzel, W A; Sanchez, P Del Amo; Barrett, M; Harrison, T J; Hart, A J; Hawkes, C M; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Sherwood, D J; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Williams, D C; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Dvoretskii, A; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Vetere, M Lo; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Nikolich, M B; Vazquez, W Panduro; Behera, P K; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Diberder, F Le; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Lodovico, F Di; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; Nardo, G De; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Losecco, J M; Benelli, G; Corwin, L A; Gan, K K; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Potter, C T; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Chauveau, J; David, P; Buono, L Del; de la Vaissière, Ch; Hamon, O; Hartfiel, B L; Leruste, Ph; Malclès, J; Ocariz, J; Gladney, L; Biasini, M

    2007-03-16

    We search for the decays B(0) --> rho(0)rho(0), B(0) --> rho(0)f(0)(980), and B(0) --> f(0)(980)f(0)(980) in a sample of about 384 x 10(6) Upsilon(4S) --> BB[over] decays collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) collider at Stanford Linear Accelerator Center. We find evidence for B(0) --> rho(0)rho(0) with 3.5 sigma significance and measure the branching fraction B = (1.07 +/- 0.33 +/- 0.19) x 10(-6) and longitudinal polarization fraction f(L) = 0.87 +/- 0.13 +/- 0.04, where the first uncertainty is statistical, and the second is systematic. The uncertainty on the Cabibbo-Kobayashi-Maskawa quark-mixing matrix unitarity angle alpha due to penguin contributions in B --> rho rho decays is 18 degrees at the 1 sigma level. We also set upper limits on the B(0) --> rho(0)f(0)(980) and B(0) --> f(0)(980)f(0)(980) decay rates.

  10. 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.)

  11. Branching fraction measurements of B+-->rho+gamma, B0-->rho0gamma, and B0-->omegagamma.

    Science.gov (United States)

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Tackmann, K; Wenzel, W A; del Amo Sanchez, P; Barrett, M; Harrison, T J; Hart, A J; Hawkes, C M; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Sherwood, D J; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Zhang, L; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Williams, D C; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Dvoretskii, A; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Nikolich, M B; Panduro Vazquez, W; Behera, P K; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Koeneke, K; Lang, M I; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Yi, M; Kim, H; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Losecco, J M; Benelli, G; Corwin, L A; Gan, K K; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Potter, C T; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Hartfiel, B L; Leruste, Ph; Malclès, J; Ocariz, J; Gladney, L; Biasini, M

    2007-04-13

    We present a study of the decays B+-->rho+gamma, B0-->rho0gamma, and B0-->omegagamma. The analysis is based on data containing 347 x 10(6) BB[over ] events recorded with the BABAR detector at the PEP-II asymmetric B factory. We measure the branching fractions B(B+-->rho+)gamma)=(1.10_(-0.33)(+0.37)+/-0.09)x10(-6) and B(B0-->rho0gamma)=(0.79(-0.20)(+0.22)+/-0.06)x10(-6), and set a 90% C.L. upper limit B(B0-->omegagamma)(rho/omega)gamma)=(1.25(-0.24)(+0.25)+/-0.09)x10(-6), from which we determine |Vtd/Vts|=0.200(-0.020)(+0.021)+/-0.015, where the first uncertainty is experimental and the second is theoretical.

  12. 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

  13. 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.

  14. 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...

  15. Control of T lymphocyte morphology by the GTPase Rho

    Directory of Open Access Journals (Sweden)

    Caudell Eva G

    2003-02-01

    Full Text Available Abstract Background Rho family GTPase regulation of the actin cytoskeleton governs a variety of cell responses. In this report, we have analyzed the role of the GTPase Rho in maintenance of the T lymphocyte actin cytoskeleton. Results Inactivation of the GTPase Rho in the human T lymphocytic cell line HPB-ALL does not inhibit constitutively high adhesion to the integrin β1 substrate fibronectin. It did however result in the aberrant extension of finger-like dendritic processes on the substrates VCAM-1, Fn, and mAb specific to β1 integrins. Time-lapse video microscopy demonstrated that C3 induced extensions were primarily the result of an altered pseudopod elongation rather than retraction. Once the stellate pseudopodia extended, none retracted, and cells became completely immobile. Filipodial structures were absent and the dendritic-like processes in C3 treated cells were rich in filamentous actin. Immunolocalization of RhoA in untreated HPB-ALL cells spreading on fibronectin demonstrated a diffuse staining pattern within the pseudopodia. In C3 treated cells, clusters of RhoA were pronounced and localized within the altered extensions. Conclusions GTPase Rho is actively involved in the regulation of T lymphocyte morphology and motility.

  16. 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

  17. 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.

  18. 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.)

  19. Thrombin generation in abdominal sepsis is Rho-kinase-dependent.

    Science.gov (United States)

    Wang, Yongzhi; Braun, Oscar Ö; Zhang, Su; Norström, Eva; Thorlacius, Henrik

    2015-05-08

    Sepsis causes severe derangements of the coagulation system. However, the signaling mechanisms regulating sepsis-induced thrombin generation remain elusive. Herein, we hypothesized that Rho-kinase might be an important regulator of thrombin generation in abdominal sepsis. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57Bl/6 mice. Thrombin generation, coagulation factors, lung histology and myeloperoxidase (MPO) activity were determined 6 h and 24 h after induction of CLP. Induction of CLP triggered a systemic inflammatory response characterized by neutrophil accumulation and tissue injury in the lung as well as thrombocytopenia and leukocytopenia. Administration of Y-27632, a Rho-kinase inhibitor, attenuated these markers of systemic inflammation in CLP animals. Moreover, peak thrombin formation was decreased by 77% and 81% in plasma from mice 6 h and 24 h after induction of CLP. Total thrombin generation was reduced by 64% and 67% 6 h and 24 h after CLP induction, respectively. Notably, administration of Y-27632 increased peak formation by 99% and total thrombin generation by 66% in plasma from septic animals. In addition, CLP markedly decreased plasma levels of prothrombin, factor V and factor X at 6 h and 24 h. Interestingly, Rho-kinase inhibition significantly enhanced levels of prothrombin, factor V and factor X in plasma from septic mice. In addition, inhibition of Rho-kinase decreased CLP-induced elevations of CXCL2 by 36% and interleukin-6 by 38%. These novel findings suggest that sepsis-induced thrombin generation is regulated by Rho-kinase. Moreover, inhibition of Rho-kinase reverses sepsis-evoked consumption of coagulation factors. Thus, our results show that targeting Rho-kinase signaling might protect against coagulation dysfunction in abdominal sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions

    Science.gov (United States)

    Budnar, Srikanth; Yap, Alpha S.

    2017-01-01

    Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model. PMID:28273072

  1. Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions.

    Directory of Open Access Journals (Sweden)

    Rashmi Priya

    2017-03-01

    Full Text Available Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model.

  2. 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.

  3. Unique Structural and Nucleotide Exchange Features of the Rho1 GTPase of Entamoeba histolytica

    Energy Technology Data Exchange (ETDEWEB)

    Bosch, Dustin E.; Wittchen, Erika S.; Qiu, Connie; Burridge, Keith; Siderovski, David P. (UNC)

    2012-08-10

    The single-celled human parasite Entamoeba histolytica possesses a dynamic actin cytoskeleton vital for its intestinal and systemic pathogenicity. The E. histolytica genome encodes several Rho family GTPases known to regulate cytoskeletal dynamics. EhRho1, the first family member identified, was reported to be insensitive to the Rho GTPase-specific Clostridium botulinum C3 exoenzyme, raising the possibility that it may be a misclassified Ras family member. Here, we report the crystal structures of EhRho1 in both active and inactive states. EhRho1 is activated by a conserved switch mechanism, but diverges from mammalian Rho GTPases in lacking a signature Rho insert helix. EhRho1 engages a homolog of mDia, EhFormin1, suggesting a role in mediating serum-stimulated actin reorganization and microtubule formation during mitosis. EhRho1, but not a constitutively active mutant, interacts with a newly identified EhRhoGDI in a prenylation-dependent manner. Furthermore, constitutively active EhRho1 induces actin stress fiber formation in mammalian fibroblasts, thereby identifying it as a functional Rho family GTPase. EhRho1 exhibits a fast rate of nucleotide exchange relative to mammalian Rho GTPases due to a distinctive switch one isoleucine residue reminiscent of the constitutively active F28L mutation in human Cdc42, which for the latter protein, is sufficient for cellular transformation. Nonconserved, nucleotide-interacting residues within EhRho1, revealed by the crystal structure models, were observed to contribute a moderating influence on fast spontaneous nucleotide exchange. Collectively, these observations indicate that EhRho1 is a bona fide member of the Rho GTPase family, albeit with unique structural and functional aspects compared with mammalian Rho GTPases.

  4. Results on exclusive $\\rho^{0}$ production from COMPASS

    CERN Document Server

    Neyret, D

    2004-01-01

    Study of the $\\rho^{0}$ spin density matrices $r^{\\alpha}_{\\gamma\\gamma'}$ using exclusive incoherent $\\rho^{0}$ production events is performed by the COMPASS collaboration. An overview of this analysis is presented, and preliminary results from the 2002 data are shown. These results are compatible with the previous experiments but with a better statistical accuracy and cover a higher range in $Q^{2}$. The ratio R of the longitudinal to transverse virtual photon polarization cross sections for the studied process is deduced from $r^{04}_{00}$. The non-zero value of $r^{04}_{1-1}$ indicates a weak violation of the s-channel helicity conservation.

  5. Targeted inhibition of renal Rho kinase reduces macrophage infiltration and lymphangiogenesis in acute renal allograft rejection

    NARCIS (Netherlands)

    Poosti, Fariba; Yazdani, Saleh; Dolman, M. Emmy M.; Kok, Robbert Jan; Chen, Cheng; Ding, Guohua; Lacombe, Marie; Prakash, Jai; van den Born, Jacob; Hillebrands, Jan-Luuk; van Goor, Harry; de Borst, Martin H.

    2012-01-01

    The Rho kinase pathway plays an important role in epithelial dedifferentiation and inflammatory cell infiltration. Recent studies suggest that inflammation promotes lymphangiogenesis, which has been associated with renal allograft rejection. We investigated whether targeted inhibition of the Rho

  6. 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 $\\mathcal B (B^0 \\to \\rho^0 \\rho^0) = (0.94 \\pm 0.17 ({\\rm stat}) \\pm 0.09 ({\\rm syst}) \\pm 0.06 ({\\rm BF})) \\times 10^{-6}$.

  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. Tuning luminescence intensity of RHO6G dye using silver ...

    Indian Academy of Sciences (India)

    Wintec

    in the presence of different amounts of citrate stabilized silver nanoparticles of size, ∼10 nm. Enhancement as well as quenching of luminescence intensity has been observed and it was found that luminescence intensity can be tuned by adding various amounts of silver nanoparticles to the RHO6G dye dispersion.

  9. 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

  10. Tuning luminescence intensity of RHO6G dye using silver ...

    Indian Academy of Sciences (India)

    Wintec

    Abstract. The photoluminescence (PL) from rhodamine (RHO6G) dye dispersed in ethanol has been studied in the presence of different amounts of citrate stabilized silver nanoparticles of size, ∼10 nm. Enhancement as well as quenching of luminescence intensity has been observed and it was found that luminescence ...

  11. Statins improve NASH via inhibition of RhoA and Ras

    DEFF Research Database (Denmark)

    Schierwagen, Robert; Maybüchen, Lara; Hittatiya, Kanishka

    2016-01-01

    in NASH. SMV blunted fibrosis due to inhibition of both RhoA/Rho kinase and Ras/ERK pathways. Interestingly, inhibition of RAC1 and Ras (by LT) failed to decrease fibrosis to the same extent. Inhibition of RAC1 (by NSC) showed no significant effect at all. Inhibition of RhoA and Ras downstream signaling...

  12. 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…

  13. RhoH is important for positive thymocyte selection and T-cell receptor signaling

    DEFF Research Database (Denmark)

    Dorn, Tatjana; Kuhn, Ursula; Bungartz, Gerd

    2006-01-01

    RhoH is a small GTPase expressed only in the hematopoietic system. With the use of mice with targeted disruption of the RhoH gene, we demonstrated that RhoH is crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Furthermore, the differentiation and expansion...

  14. 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

  15. 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

  16. 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)

  17. 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.

  18. Implementation of Pollard Rho over binary fields using Brent Cycle Detection Algorithm

    Science.gov (United States)

    Muchtadi-Alamsyah, Intan; Akbari Utomo, Taufiq

    2017-10-01

    The security of Elliptic Curve Cryptography depends on how to solve the Elliptic Curve Cryptography Discrete Logarithm Problem (ECDLP). In this paper we propose the use of modified Pollard Rho Algorithm by using Brent Cycle Detection Algorithm to solve the ECDLP. We give performance comparison on time and the number of iterations between Pollard Rho with Brent Cycle Detection and Pollard Rho with Negation map. In particular, for Koblitz curve, we also give comparison between Pollard Rho with Brent Cycle Detection and Pollard Rho with Negation and Frobenius maps.

  19. 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.

  20. 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

    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......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...

  1. 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.

  2. 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.

  3. Measuring the Higgs boson's parity using $\\tau \\to \\rho\

    CERN Document Server

    Bower, G R; Was, Zbigniew; Worek, M

    2002-01-01

    We present a very promising method for a measurement of the Higgs boson parity using the H/A -> tau^+ tau^- --> rho^+ nu rho^- nu --> pi^+ pi^0 nu pi^- pi^0 nu decay chain. The method is both model independent and independent of the Higgs production mechanism. Angular distributions of the tau decay products which are sensitive to the Higgs boson parity are defined and are found to be measurable using typical properties of a future detector for an e^+ e^- linear collider. The prospects for the measurement of the parity of a Higgs boson with a mass of 120 GeV are quantified for the case of e^+ e^- collisons of 500 GeV center of mass energy with an integrated luminosity of 500 fb^-1. The Standard Model Higgsstrahlung production process is used as an example.

  4. 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

    -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...

  5. 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.

  6. 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

    , resulting in a specific decrease in affinity for RhoA, but not Rac1 or cdc42. The mechanism of RhoGDIalpha phosphorylation is distinct, requiring PKCalpha and phosphatidylinositol 4,5 bisphosphate, consistent with recent evidence that the inositide can activate, localize and orient PKCalpha in membranes...

  7. 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)

  8. 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

  9. 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

  10. 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.

  11. Ethanol increases p190RhoGAP activity, leading to actin cytoskeleton rearrangements.

    Science.gov (United States)

    Selva, Javier; Egea, Gustavo

    2011-12-01

    We previously reported that cells chronically exposed to ethanol show alterations in actin cytoskeleton organization and dynamics in primary cultures of newborn rat astrocytes, a well-established in vitro model for foetal alcohol spectrum disorders. These alterations were attributed to a decrease in the cellular levels of active RhoA (RhoA-GTP), which in turn was produced by an increase in the total RhoGAP activity. We here provide evidence that p190RhoGAPs are the main factors responsible for such increase. Thus, in astrocytes chronically exposed to ethanol we observe: (i) an increase in p190A- and p190B-associated RhoGAP activity; (ii) a higher binding of p190A and p190B to RhoA-GTP; (iii) a higher p120RasGAP-p190A RhoGAP complex formation; and (iv) the recruitment of both p190RhoGAPs to the plasma membrane. The simultaneous silencing of both p190 isoforms prevents the actin rearrangements and the total RhoGAP activity increase triggered both by ethanol. Therefore, our data directly points p190RhoGAPs as ethanol-exposure molecular targets on glial cells of the CNS. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  12. GTPases Rho distribution in intraepithelial and invasive neoplasias of the uterine cervix.

    Science.gov (United States)

    Tibúrcio, M Gomes Salles; Pinheiro, N M; Carboni, S de Sales Costa Moreira; Rocha, L P; Adad, S J; Maluf, P J; Murta, E F Cândido; Crema, V O

    2014-01-01

    To evaluate the distribution of GTPases RhoA, RhoB, and Cdc42 in cervical intraepithelial neoplasias (CIN) and invasive neoplasias of the uterine cervix. samples of neoplastic lesions of the uterine cervix of 44 patients were classified in: CIN I (n = 10), CIN II (n = 10), CIN III (n = 09), and invasive carcinoma (n = 15). Antibodies anti-RhoA, anti-RhoB, and anti-Cdc42 were used and staining was classified as: negative, mild, moderate, and intense positive. When compared with dysplastic cells, superficial cells showed: higher expression of RhoB in CIN I (p = 0.0018), and lower expression of Cdc42 in CIN I (p = 0.0225). The authors observed higher expression of RhoA (p = 0.0002) and RhoB (p = 0.0046) in CIN dysplastic cells when compared with invasive carcinoma cells. GTPases Rho may be involved with the regulation of biological processes, important to the progression of cervical neoplasias. Probably, RhoA is important for maintenance of cell differentiation and RhoB protects cells from malignant cervical neoplasia.

  13. Proteomics Core

    Data.gov (United States)

    Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in a...

  14. EXTERNALLY HEATED PROTOSTELLAR CORES IN THE OPHIUCHUS STAR-FORMING REGION

    Energy Technology Data Exchange (ETDEWEB)

    Lindberg, Johan E.; Charnley, Steven B.; Cordiner, Martin A. [NASA Goddard Space Flight Center, Astrochemistry Laboratory, Mail Code 691, 8800 Greenbelt Road, Greenbelt, MD 20771 (United States); Jørgensen, Jes K.; Bjerkeli, Per, E-mail: johan.lindberg@nasa.gov [Centre for Star and Planet Formation, Niels Bohr Institute and Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen K (Denmark)

    2017-01-20

    We present APEX 218 GHz observations of molecular emission in a complete sample of embedded protostars in the Ophiuchus star-forming region. To study the physical properties of the cores, we calculate H{sub 2}CO and c -C{sub 3}H{sub 2} rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H{sub 2}CO temperatures range between 16 K and 124 K, with the highest H{sub 2}CO temperatures toward the hot corino source IRAS 16293-2422 (69–124 K) and the sources in the ρ Oph A cloud (23–49 K) located close to the luminous Herbig Be star S1, which externally irradiates the ρ Oph A cores. On the other hand, the c -C{sub 3}H{sub 2} rotational temperature is consistently low (7–17 K) in all sources. Our results indicate that the c -C{sub 3}H{sub 2} emission is primarily tracing more shielded parts of the envelope whereas the H{sub 2}CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS 16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow.

  15. Function of small GTPase Rho3 in regulating growth, conidiation and virulence of Botrytis cinerea.

    Science.gov (United States)

    An, Bang; Li, Boqiang; Qin, Guozheng; Tian, Shiping

    2015-02-01

    Small GTPases of the Rho family play an important role in regulating biological processes in fungi. In this study, we mainly investigated the biological functions of Rho3 in Botrytis cinerea, and found that deletion of the rho3 from B. cinerea significantly suppressed vegetative growth and conidiation, reduced appressorium formation and decreased virulence. Microscopy analysis revealed that the distance between septa was increased in the Δrho3 mutant. In addition, mitochondria were suggested to be the main sources of intracellular reactive oxygen species (ROS) in B. cinerea based on dual staining with 2',7'-dichlorodihydrofluorescein diacetate and MitoTracker orange. The Δrho3 mutant showed less accumulation of ROS in the hyphae tips compared to the WT strain of B. cinerea. These results provide the novel evidence to ascertain the function of small GTPase Rho3 in regulating growth, conidiation and virulence of B. cinerea. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 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.

  17. 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.

  18. 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.

  19. Use of d-3He proton spectroscopy as a diagnostic of shell rho r in capsule implosion experiments with approximately 0.2 NIF scale high temperature Hohlraums at Omega.

    Science.gov (United States)

    Delamater, N D; Wilson, D C; Kyrala, G A; Seifter, A; Hoffman, N M; Dodd, E; Singleton, R; Glebov, V; Stoeckl, C; Li, C K; Petrasso, R; Frenje, J

    2008-10-01

    We present the calculations and preliminary results from experiments on the Omega laser facility using d-(3)He filled plastic capsule implosions in gold Hohlraums. These experiments aim to develop a technique to measure shell rho r and capsule unablated mass with proton spectroscopy and will be applied to future National Ignition Facility (NIF) experiments with ignition scale capsules. The Omega Hohlraums are 1900 microm length x 1200 microm diameter and have a 70% laser entrance hole. This is approximately a 0.2 NIF scale ignition Hohlraum and reaches temperatures of 265-275 eV similar to those during the peak of the NIF drive. These capsules can be used as a diagnostic of shell rho r, since the d-(3)He gas fill produces 14.7 MeV protons in the implosion, which escape through the shell and produce a proton spectrum that depends on the integrated rho r of the remaining shell mass. The neutron yield, proton yield, and spectra change with capsule shell thickness as the unablated mass or remaining capsule rho r changes. Proton stopping models are used to infer shell unablated mass and shell rho r from the proton spectra measured with different filter thicknesses. The experiment is well modeled with respect to Hohlraum energetics, neutron yields, and x-ray imploded core image size, but there are discrepancies between the observed and simulated proton spectra.

  20. Identification of Rho GTPases implicated in terminal differentiation of muscle cells in ascidia.

    Science.gov (United States)

    Coisy-Quivy, Marjorie; Sanguesa-Ferrer, Juan; Weill, Mylène; Johnson, David Scott; Donnay, Jean-Marc; Hipskind, Robert; Fort, Philippe; Philips, Alexandre

    2006-10-01

    Members of the Rho GTPase family mediate changes in the actin cytoskeleton and are also implicated in developmental processes, including myogenesis. Nevertheless, a comprehensive analysis of these proteins during myofibrillogenesis has never been performed in any organism. Using the ascidian model to identify the role of Rho GTPases on myofibrillogenesis, we show that transcripts for all Rho GTPases are detected in muscle cells of the embryo. We find that activation of RhoA, TC10 and Cdc42 (cell division cycle 42) disturbs the polarity of muscle cells, whereas that of other Rho GTPases induced cell positioning defects. Moreover, dominant negative version of five Rho GTPases, RhoA, Rac2, RCL2 (Rac- and Cdc42-like 2), TC10 and WRCH (Wnt-1 responsive Cdc42 homologue), impaired the formation of mature myofibrils. Taken together, our results show that several Rho GTPase-dependent pathways are required to control the spatial localization of muscle cells in the embryo and to coordinate myofibril assembly. This stresses the importance of analysing the entire Rho family when studying a new biological process.

  1. 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...... DGKζ functions as a scaffold to assemble a signaling complex that functions as a RhoA-selective, GDI dissociation factor. As a regulator of Rac1 and RhoA activity, DGKζ is a critical factor linking changes in lipid signaling to actin reorganization....

  2. Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK.

    Directory of Open Access Journals (Sweden)

    Romina P Salinas

    Full Text Available The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that process.

  3. The RhoU/Wrch1 Rho GTPase gene is a common transcriptional target of both the gp130/STAT3 and Wnt-1 pathways

    Science.gov (United States)

    SCHIAVONE, Davide; DEWILDE, Sarah; VALLANIA, Francesco; TURKSON, James; CUNTO, Ferdinando DI; POLI, Valeria

    2010-01-01

    STAT3 (signal transducer and activator of transcription 3) is a transcription factor activated by cytokines, growth factors and oncogenes, whose activity is required for cell survival/proliferation of a wide variety of primary tumours and tumour cell lines. Prominent among its multiple effects on tumour cells is the stimulation of cell migration and metastasis, whose functional mechanisms are however not completely characterized. RhoU/Wrch1 (Wnt-responsive Cdc42 homologue) is an atypical Rho GTPase thought to be constitutively bound to GTP. RhoU was first identified as a Wnt-1-inducible mRNA and subsequently shown to act on the actin cytoskeleton by stimulating filopodia formation and stress fibre dissolution. It was in addition recently shown to localize to focal adhesions and to Src-induced podosomes and enhance cell migration. RhoU overexpression in mammary epithelial cells stimulates quiescent cells to re-enter the cell cycle and morphologically phenocopies Wnt-1-dependent transformation. In the present study we show that Wnt-1-mediated RhoU induction occurs at the transcriptional level. Moreover, we demonstrate that RhoU can also be induced by gp130 cytokines via STAT3, and we identify two functional STAT3-binding sites on the mouse RhoU promoter. RhoU induction by Wnt-1 is independent of β-catenin, but does not involve STAT3. Rather, it is mediated by the Wnt/planar cell polarity pathway through the activation of JNK (c-Jun N-terminal kinase). Both the so-called non-canonical Wnt pathway and STAT3 are therefore able to induce RhoU, which in turn may be involved in mediating their effects on cell migration. PMID:19397496

  4. 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.

  5. 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...

  6. 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

  7. The small GTPase RhoB regulates TNFα signaling in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Jeffrey Kroon

    Full Text Available The inflammatory response of endothelial cells triggered by cytokines such as TNFα and IL1β plays a pivotal role in innate immunity. Upon pro-inflammatory cytokine stimulation, endothelial cells produce chemokines and cytokines that attract and activate leukocytes, and express high levels of leukocyte adhesion molecules. This process is mediated by intracellular signaling cascades triggered by activation of e.g. the TNFα receptor (TNFR that lead to the activation of the NFκB transcription factor and of MAP kinases, which in turn activate inflammatory gene transcription. We found that the small GTPase RhoB was strongly and rapidly upregulated in primary human endothelial cells by TNFα, IL1β and LPS. We subsequently investigated the role of RhoB in the regulation of TNFR signaling in endothelial cells by silencing RhoB expression with siRNA. We provide evidence that the TNFα-induced activation of p38 MAP kinase is strongly dependent on RhoB, but not on RhoA, while JNK activation is regulated by both RhoB and RhoA. Consistent with the important role of p38 MAP kinase in inflammation, we demonstrate that loss of RhoB impairs TNFα-induced ICAM-1 expression and reduces cell production of IL6 and IL8. In addition, we show that RhoB silencing alters the intracellular traffic of TNFα after endocytosis. Since RhoB is a known regulator of the intracellular traffic of membrane receptors, our data suggest that RhoB controls TNFα signaling through the regulation of the TNFR traffic.

  8. 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

  9. 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

  10. Toward understanding RhoGTPase specificity: structure, function and local activation

    NARCIS (Netherlands)

    Schaefer, Antje; Reinhard, Nathalie R.; Hordijk, Peter L.

    2014-01-01

    Cell adhesion and migration are regulated through the concerted action of cytoskeletal dynamics and adhesion proteins, the activity of which is governed by RhoGTPases. Specific RhoGTPase signaling requires spatio-temporal activation and coordination of subsequent protein-protein and protein-lipid

  11. Activation of RhoA and ROCK Are Essential for Detachment of Migrating Leukocytesh

    NARCIS (Netherlands)

    Alblas, J.; Ulfman, L.H.; Hordijk, Peter; Koenderman, L.

    2000-01-01

    Detachment of the rear of the cell from its substratum is an important aspect of locomotion. The signaling routes involved in this adhesive release are largely unknown. One of the few candidate proteins to play a role is RhoA, because activation of RhoA in many cell types leads to contraction, a

  12. 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

  13. 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

  14. The RhoJ-BAD signaling network: An Achilles' heel for BRAF mutant melanomas.

    Directory of Open Access Journals (Sweden)

    Rolando Ruiz

    2017-07-01

    Full Text Available Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. In this study, we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a BAD-dependent mechanism. As up to 50% of BRAF mutant human melanomas express high levels of RhoJ, these studies nominate the RhoJ-BAD signaling network as a therapeutic vulnerability for fledgling BRAF mutant human tumors.

  15. The RhoJ-BAD signaling network: An Achilles' heel for BRAF mutant melanomas.

    Science.gov (United States)

    Ruiz, Rolando; Jahid, Sohail; Harris, Melissa; Marzese, Diego M; Espitia, Francisco; Vasudeva, Priya; Chen, Chi-Fen; de Feraudy, Sebastien; Wu, Jie; Gillen, Daniel L; Krasieva, Tatiana B; Tromberg, Bruce J; Pavan, William J; Hoon, Dave S; Ganesan, Anand K

    2017-07-01

    Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered. In this study, we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells. RhoJ deletion in BRAF mutant melanocytes modulates the expression of the pro-apoptotic protein BAD as well as genes involved in cellular metabolism, impairing nevus formation, cellular transformation, and metastasis. Short-term treatment of nascent melanoma tumors with PAK inhibitors that block RhoJ signaling halts the growth of BRAF mutant melanoma tumors in vivo and induces apoptosis in melanoma cells in vitro via a BAD-dependent mechanism. As up to 50% of BRAF mutant human melanomas express high levels of RhoJ, these studies nominate the RhoJ-BAD signaling network as a therapeutic vulnerability for fledgling BRAF mutant human tumors.

  16. 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....

  17. Rho-kinase inhibition ameliorates metabolic disorders through activation of AMPK pathway in mice.

    Directory of Open Access Journals (Sweden)

    Kazuki Noda

    Full Text Available BACKGROUND: Metabolic disorders, caused by excessive calorie intake and low physical activity, are important cardiovascular risk factors. Rho-kinase, an effector protein of the small GTP-binding protein RhoA, is an important cardiovascular therapeutic target and its activity is increased in patients with metabolic syndrome. We aimed to examine whether Rho-kinase inhibition improves high-fat diet (HFD-induced metabolic disorders, and if so, to elucidate the involvement of AMP-activated kinase (AMPK, a key molecule of metabolic conditions. METHODS AND RESULTS: Mice were fed a high-fat diet, which induced metabolic phenotypes, such as obesity, hypercholesterolemia and glucose intolerance. These phenotypes are suppressed by treatment with selective Rho-kinase inhibitor, associated with increased whole body O2 consumption and AMPK activation in the skeletal muscle and liver. Moreover, Rho-kinase inhibition increased mRNA expression of the molecules linked to fatty acid oxidation, mitochondrial energy production and glucose metabolism, all of which are known as targets of AMPK in those tissues. In systemic overexpression of dominant-negative Rho-kinase mice, body weight, serum lipid levels and glucose metabolism were improved compared with littermate control mice. Furthermore, in AMPKα2-deficient mice, the beneficial effects of fasudil, a Rho-kinase inhibitor, on body weight, hypercholesterolemia, mRNA expression of the AMPK targets and increase of whole body O2 consumption were absent, whereas glucose metabolism was restored by fasudil to the level in wild-type mice. In cultured mouse myocytes, pharmacological and genetic inhibition of Rho-kinase increased AMPK activity through liver kinase b1 (LKB1, with up-regulation of its targets, which effects were abolished by an AMPK inhibitor, compound C. CONCLUSIONS: These results indicate that Rho-kinase inhibition ameliorates metabolic disorders through activation of the LKB1/AMPK pathway, suggesting that

  18. RhoA Ambivalently Controls Prominent Myofibroblast Characteritics by Involving Distinct Signaling Routes.

    Directory of Open Access Journals (Sweden)

    Aline Jatho

    Full Text Available RhoA has been shown to be beneficial in cardiac disease models when overexpressed in cardiomyocytes, whereas its role in cardiac fibroblasts (CF is still poorly understood. During cardiac remodeling CF undergo a transition towards a myofibroblast phenotype thereby showing an increased proliferation and migration rate. Both processes involve the remodeling of the cytoskeleton. Since RhoA is known to be a major regulator of the cytoskeleton, we analyzed its role in CF and its effect on myofibroblast characteristics in 2 D and 3D models.Downregulation of RhoA was shown to strongly affect the actin cytoskeleton. It decreased the myofibroblast marker α-sm-actin, but increased certain fibrosis-associated factors like TGF-β and collagens. Also, the detailed analysis of CTGF expression demonstrated that the outcome of RhoA signaling strongly depends on the involved stimulus. Furthermore, we show that proliferation of myofibroblasts rely on RhoA and tubulin acetylation. In assays accessing three different types of migration, we demonstrate that RhoA/ROCK/Dia1 are important for 2D migration and the repression of RhoA and Dia1 signaling accelerates 3D migration. Finally, we show that a downregulation of RhoA in CF impacts the viscoelastic and contractile properties of engineered tissues.RhoA positively and negatively influences myofibroblast characteristics by differential signaling cascades and depending on environmental conditions. These include gene expression, migration and proliferation. Reduction of RhoA leads to an increased viscoelasticity and a decrease in contractile force in engineered cardiac tissue.

  19. 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.)

  20. Methanol conversion to lower olefins over RHO type zeolite

    KAUST Repository

    Masih, Dilshad

    2013-07-01

    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 specific surface area (812 m2 g-1), micropore volume (0.429 cm3 g-1), and acid amount (2.53 mmol g-1). Scanning electron microscopy observations showed small crystallites of about 1 μm. The zeolite was active for MTO reaction with 100% methanol conversions at 623-723 K, whereas selectivity to lower olefins changed with time. © 2013 Elsevier B.V.

  1. Exclusive $\\rho^0$ muoproduction on transversely polarised protons and deuterons

    CERN Document Server

    Adolph, C.; Alexakhin, V.Yu.; Alexandrov, Yu.; Alexeev, G.D.; Amoroso, A.; Antonov, A.A.; Austregesilo, A.; Badelek, B.; Balestra, F.; Barth, J.; Baum, G.; Bedfer, Y.; Bernhard, J.; Bertini, R.; Bettinelli, M.; Bicker, K.; Bieling, J.; Birsa, R.; Bisplinghoff, J.; Bordalo, P.; Bradamante, F.; Braun, C.; Bravar, A.; Bressan, A.; Buchele, M.; Burtin, E.; Capozza, L.; Chiosso, M.; Chung, S.U.; Cicuttin, A.; Crespo, M.L.; Dalla Torre, S.; Das, S.; Dasgupta, S.S.; Dasgupta, S.; Denisov, O.Yu.; Dhara, L.; Donskov, S.V.; Doshita, N.; Duic, V.; Dunnweber, W.; Dziewiecki, M.; Efremov, A.; Elia, C.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Ferrero, A.; Filin, A.; Finger, M.; Finger, M., Jr.; Fischer, H.; Franco, C.; du Fresne von Hohenesche, N.; Friedrich, J.M.; Frolov, V.; Garfagnini, R.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Geyer, R.; Giorgi, M.; Gnesi, I.; Gobbo, B.; Goertz, S.; Grabmuller, S.; Grasso, A.; Grube, B.; Gushterski, R.; Guskov, A.; Guthorl, T.; Haas, F.; von Harrach, D.; Heinsius, F.H.; Herrmann, F.; Hess, C.; Hinterberger, F.; Horikawa, N.; Hoppner, Ch.; d'Hose, N.; Ishimoto, S.; Ivanov, O.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jary, V.; Jasinski, P.; Jegou, G.; Joosten, R.; Kabuss, E.; Kang, D.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu.A.; Kisselev, Yu.; Klein, F.; Klimaszewski, K.; Koblitz, S.; Koivuniemi, J.H.; Kolosov, V.N.; Kondo, K.; Konigsmann, K.; Konorov, I.; Konstantinov, V.F.; Korzenev, A.; Kotzinian, A.M.; Kouznetsov, O.; Kramer, M.; Kroumchtein, Z.V.; Kunne, F.; Kurek, K.; Lauser, L.; Lednev, A.A.; Lehmann, A.; Levorato, S.; Lichtenstadt, J.; Liska, T.; Maggiora, A.; Magnon, A.; Makke, N.; Mallot, G.K.; Mann, A.; Marchand, C.; Martin, A.; Marzec, J.; Matsuda, T.; Meshcheryakov, G.; Meyer, W.; Michigami, T.; Mikhailov, Yu.V.; Moinester, M.A.; Morreale, A.; Mutter, A.; Nagaytsev, A.; Nagel, T.; Negrini, T.; Nerling, F.; Neubert, S.; Neyret, D.; Nikolaenko, V.I.; Nowak, W.D.; Nunes, A.S.; Olshevsky, A.G.; Ostrick, M.; Padee, A.; Panknin, R.; Panzieri, D.; Parsamyan, B.; Paul, S.; Perevalova, E.; Pesaro, G.; Peshekhonov, D.V.; Piragino, G.; Platchkov, S.; Pochodzalla, J.; Polak, J.; Polyakov, V.A.; Pretz, J.; Quaresma, M.; Quintans, C.; Rajotte, J.F.; Ramos, S.; Rapatsky, V.; Reicherz, G.; Richter, A.; Rocco, E.; Rondio, E.; Rossiyskaya, N.S.; Ryabchikov, D.I.; Samoylenko, V.D.; Sandacz, A.; Sapozhnikov, M.G.; Sarkar, S.; Savin, I.A.; Sbrizzai, G.; Schiavon, P.; Schill, C.; Schluter, T.; Schmidt, K.; Schmitt, L.; Schonning, K.; Schopferer, S.; Schott, M.; Schroder, W.; Shevchenko, O.Yu.; Silva, L.; Sinha, L.; Sissakian, A.N.; Slunecka, M.; Smirnov, G.I.; Sosio, S.; Sozzi, F.; Srnka, A.; Steiger, L.; Stolarski, M.; Sulc, M.; Sulej, R.; Suzuki, H.; Sznajder, P.; Takekawa, S.; Ter Wolbeek, J.; Tessaro, S.; Tessarotto, F.; Tkatchev, L.G.; Uhl, S.; Uman, I.; Vandenbroucke, M.; Virius, M.; Vlassov, N.V.; Wang, L.; Wilfert, M.; Windmolders, R.; Wislicki, W.; Wollny, H.; Zaremba, K.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.; Zhuravlev, N.; Zvyagin, A.

    2012-01-01

    The transverse target spin azimuthal asymmetry A_UT in hard exclusive production of rho^0 mesons was measured at COMPASS by scattering 160 GeV/c muons off transversely polarised protons and deuterons. The measured asymmetry is sensitive to the nucleon helicity-flip generalised parton distributions E^q, which are related to the orbital angular momentum of quarks in the nucleon. The Q^2, x_B and p_t^2 dependence of A_UT is presented in a wide kinematic range. Results for deuterons are obtained for the first time. The measured asymmetry is small in the whole kinematic range for both protons and deuterons, which is consistent with the theoretical interpretation that contributions from GPDs E^u and E^d approximately cancel.

  2. Transverse target spin asymmetries in exclusive $\\rho^0$ muoproduction

    CERN Document Server

    Adolph, C; Alexakhin, V Yu; Alexandrov, Yu; Alexeev, G D; Amoroso, A; Andrieux, V; Austregesilo, A; Badelek, B; Balestra, F; Barth, J; Baum, G; Bedfer, Y; Berlin, A; Bernhard, J; Bertini, R; Bicker, K; Bieling, J; Birsa, R; Bisplinghoff, J; Boer, M; Bordalo, P; Bradamante, F; Braun, C; Bravar, A; Bressan, A; Büchele, M; Burtin, E; Capozza, L; Chiosso, M; Chung, S U; Cicuttin, A; Crespo, M L; Dalla Torre, S; Dasgupta, S S; Dasgupta, S; Denisov, O Yu; Donskov, S V; Doshita, N; Duic, V; Dünnweber, W; Dziewiecki, M; Efremov, A; Elia, C; Eversheim, P D; Eyrich, W; Faessler, M; Ferrero, A; Filin, A; Finger, M; Finger, M jr; Fischer, H; Franco, C; du Fresne von Hohenesche, N; Friedrich, J M; Frolov, V; Garfagnini, R; Gautheron, F; Gavrichtchouk, O P; Gerassimov, S; Geyer, R; Giorgi, M; Gnesi, I; Gobbo, B; Goertz, S; Grabmüller, S; Grasso, A; Grube, B; Gushterski, R; Guskov, A; Guthörl, T; Haas, F; von Harrach, D; Hahne, D; Heinsius, F H; Herrmann, F; Hess, C; Hinterberger, F; Höppner, Ch; Horikawa, N; d'Hose, N; Huber, S; Ishimoto, S; Ivanshin, Yu; Iwata, T; Jahn, R; Jary, V; Jasinski, P; Joosten, R; Kabuss, E; Kang, D; Ketzer, B; Khaustov, G V; Khokhlov, Yu A; Kisselev, Yu; Klein, F; Klimaszewski, K; Koivuniemi, J H; Kolosov, V N; Kondo, K; Königsmann, K; Konorov, I; Konstantinov, V F; Kotzinian, A M; Kouznetsov, O; Krämer, M; Kroumchtein, Z V; Kuchinski, N; Kunne, F; Kurek, K; Kurjata, R P; Lednev, A A; Lehmann, A; Levorato, S; Lichtenstadt, J; Maggiora, A; Magnon, A; Makke, N; Mallot, G K; Marchand, C; Martin, A; Marzec, J; Matousek, J; Matsuda, H; Matsuda, T; Meshcheryakov, G; Meyer, W; Michigami, T; Mikhailov, Yu V; Miyachi, Y; Morreale, A; Nagaytsev, A; Nagel, T; Nerling, F; Neubert, S; Neyret, D; Nikolaenko, V I; Novy, J; Nowak, W D; Nunes, A.S; Olshevsky, A G; Ostrick, M; Panknin, R; Panzieri, D; Parsamyan, B; Paul, S; Pesek, M; Piragino, G; Platchkov, S; Pochodzalla, J; Polak, J; Polyakov, V A; Pretz, J; Quaresma, M; Quintans, C; Ramos, S; Reicherz, G; Rocco, E; Rodionov, V; Rondio, E; Rossiyskaya, N S; Ryabchikov, D I; Samoylenko, V D; Sandacz, A; Sapozhnikov, M G; Sarkar, S; Savin, I A; Sbrizzai, G; Schiavon, P; Schill, C; Schlüter, T; Schmidt, A; Schmidt, K; Schmitt, L; Schmïden, H; Schönning, K; Schopferer, S; Schott, M; Shevchenko, O Yu; Silva, L; Sinha, L; Sirtl, S; Slunecka, M; Sosio, S; Sozzi, F; Srnka, A; Steiger, L; Stolarski, M; Sulc, M; Sulej, R; Suzuki, H; Sznajder, P; Takekawa, S; Ter Wolbeek, J; Tessaro, S; Tessarotto, F; Thibaud, F; Uhl, S; Uman, I; Vandenbroucke, M; Virius, M; Vondra, J; Wang, L; Weisrock, T; Wilfert, M; Windmolders, R; Wislicki, W; Wollny, H; Zaremba, K; Zavertyaev, M; Zemlyanichkina, E; Zhuravlev, N; Ziembicki, M

    2014-01-01

    Exclusive production of $\\rho^0$ mesons was studied at the COMPASS experiment by scattering 160 GeV/$c$ muons off transversely polarised protons. Five single-spin and three double-spin azimuthal asymmetries were measured as a function of $Q^2$, $x_{Bj}$, or $p_{T}^{2}$. The $\\sin \\phi_S$ asymmetry is found to be $-0.019 \\pm 0.008(stat.) \\pm 0.003(syst.)$. All other asymmetries are also found to be of small magnitude and consistent with zero within experimental uncertainties. Very recent calculations using a GPD-based model agree well with the present results. The data is interpreted as evidence for the existence of chiral-odd, transverse generalized parton distributions.

  3. Diffractive electroproduction of {rho} and {phi} mesons at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Aaron, F.D. [National Inst. for Physics and Nuclear Engineering (NIPNE), Bucharest (Romania); Bucharest Univ. (Romania). Faculty of Physics; Aldaya Martin, M. [DESY Hamburg (Germany); Alexa, C. [National Inst. for Physics and Nuclear Engineering (NIPNE), Bucharest (RO)] (and others)

    2009-06-15

    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{sup -1}. About 10500 {rho} and 2000 {phi} events are analysed in the kinematic range of squared photon virtuality 2.5{<=}Q{sup 2}{<=}60 GeV{sup 2}, photon-proton centre of mass energy 35{<=}W{<=}180 GeV and squared four-momentum transfer to the proton vertical stroke 3 vertical stroke {<=} GeV{sup 2}. The total, longitudinal and transverse cross sections are measured as a function of Q{sup 2}, W and vertical stroke 3 vertical stroke. The measurements show a transition to a dominantly ''hard'' behaviour, typical of high gluon densities and small q anti q dipoles, for Q{sup 2} larger than 10 to 20 GeV{sup 2}. They support flavour independence of the diffractive exchange, expressed in terms of the scaling variable (Q{sup 2}+M{sub V}{sup 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, the ratio of the helicity amplitudes and their relative phases are extracted. Several of these measurements have not been performed before and bring new information on the dynamics of diffraction in a QCD framework. The measurements are discussed in the context of models using generalised parton distributions or universal dipole cross sections. (orig.)

  4. HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats without major systemic effects

    NARCIS (Netherlands)

    Klein, Sabine; Van Beuge, Marike Marjolijn; Granzow, Michaela; Beljaars, Leonie; Schierwagen, Robert; Kilic, Sibel; Heidari, Iren; Huss, Sebastian; Sauerbruch, Tilman; Poelstra, Klaas; Trebicka, Jonel

    2012-01-01

    Background & Aims: Rho-kinase activation mediates cell contraction and increases intrahepatic resistance and consequently portal pressure in liver cirrhosis. Systemic Rho-kinase inhibition decreases portal pressure in cirrhosis, but also arterial pressure. Thus, liver-specific Rho-kinase inhibition

  5. Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

    DEFF Research Database (Denmark)

    Arildsen, Nicolai Skovbjerg; Jönsson, Jenny-Maria; Bartuma, Katarina

    2017-01-01

    OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyondARID1A, which...... and ultimately improve patient outcome. METHODS: Gene expression profiling of formalin-fixed, paraffin-embedded (FFPE) tissue from a cohort of the major ovarian cancer subtypes (cohort 1;n = 67) was performed using whole-genome cDNA-mediated Annealing, Selection, extension and Ligation (WG-DASL) bead arrays...... ovarian cancer subtypes. However, overexpression ofERBB2was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct...

  6. 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

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Jiwon [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Department of Microbiology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Choi, Jeong-Hae; Won, Misun [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Gyun, Mi-Rang [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Functional Genomics, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of); Park, Hee-Moon [Department of Microbiology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Chun-Ho, E-mail: chkim@kirams.re.kr [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Chung, Kyung-Sook, E-mail: kschung@kribb.re.kr [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-06-03

    Highlights: {yields} Regulation of transcriptional activation of RhoB is still unclear. {yields} We examine the effect of p38 MAPK inhibition, and c-Jun and RhoB depletion on UV-induced RhoB expression and apoptosis. {yields} We identify the regions of RhoB promoter necessary to confer UV responsiveness using pRhoB-luciferase reporter assays. {yields} c-Jun, ATF2 and p300 are dominantly associated with NF-Y on the distal CCAAT box. {yields} 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

  7. Effects of Rho1, a small GTPase on the production of recombinant glycoproteins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Xu, Sha; Zhang, Ge-Yuan; Zhang, Huijie; Kitajima, Toshihiko; Nakanishi, Hideki; Gao, Xiao-Dong

    2016-10-21

    To humanize yeast N-glycosylation pathways, genes involved in yeast specific hyper-mannosylation must be disrupted followed by the introduction of genes catalyzing the synthesis, transport, and addition of human sugars. However, deletion of these genes, for instance, OCH1, which initiates hyper-mannosylation, could cause severe defects in cell growth, morphogenesis and response to environmental challenges. In this study, overexpression of RHO1, which encodes the Rho1p small GTPase, is confirmed to partially recover the growth defect of Saccharomyces cerevisiae Δalg3Δoch1 double mutant strain. In addition, transmission electron micrographs indicated that the cell wall structure of RHO1-expressed cells have an enhanced glucan layer and also a recovered mannoprotein layer, revealing the effect of Rho1p GTPase on cell wall biosynthesis. Similar complementation phenotypes have been confirmed by overexpression of the gene that encodes Fks2 protein, a catalytic subunit of a 1,3-β-glucan synthase. Besides the recovery of cell wall structure, the RHO1-overexpressed Δalg3Δoch1 strain also showed improved abilities in temperature tolerance, osmotic potential and drug sensitivity, which were not observed in the Δalg3Δoch1-FKS2 cells. Moreover, RHO1 overexpression could also increase N-glycan site occupancy and the amount of secreted glycoproteins. Overexpression of RHO1 in 'humanized' glycoprotein producing yeasts could significantly facilitate its future industrial applications for the production of therapeutic glycoproteins.

  8. 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.

  9. 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

  10. 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.

  11. The RhoGEF TEM4 Regulates Endothelial Cell Migration by Suppressing Actomyosin Contractility.

    Directory of Open Access Journals (Sweden)

    Natalia Mitin

    Full Text Available Persistent cellular migration requires efficient protrusion of the front of the cell, the leading edge where the actin cytoskeleton and cell-substrate adhesions undergo constant rearrangement. Rho family GTPases are essential regulators of the actin cytoskeleton and cell adhesion dynamics. Here, we examined the role of the RhoGEF TEM4, an activator of Rho family GTPases, in regulating cellular migration of endothelial cells. We found that TEM4 promotes the persistence of cellular migration by regulating the architecture of actin stress fibers and cell-substrate adhesions in protruding membranes. Furthermore, we determined that TEM4 regulates cellular migration by signaling to RhoC as suppression of RhoC expression recapitulated the loss-of-TEM4 phenotypes, and RhoC activation was impaired in TEM4-depleted cells. Finally, we showed that TEM4 and RhoC antagonize myosin II-dependent cellular contractility and the suppression of myosin II activity rescued the persistence of cellular migration of TEM4-depleted cells. Our data implicate TEM4 as an essential regulator of the actin cytoskeleton that ensures proper membrane protrusion at the leading edge of migrating cells and efficient cellular migration via suppression of actomyosin contractility.

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

    Science.gov (United States)

    Kawaguchi, Mamiya; Matsuzaki, Shinya

    2017-04-01

    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 sz=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 sz=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 sz = ± 1 monotonically increase as the magnetic field develops. The correlation between the polarization dependence and the Landau level truncation is also addressed.

  13. 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.

  14. 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.

  15. 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

  16. 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....

  17. Cdc42p and Rho1p are sequentially activated and mechanistically linked to vacuole membrane fusion

    International Nuclear Information System (INIS)

    Logan, Michael R.; Jones, Lynden; Eitzen, Gary

    2010-01-01

    Small monomeric GTPases act as molecular switches, regulating many biological functions via activation of membrane localized signaling cascades. Activation of their switch function is controlled by GTP binding and hydrolysis. Two Rho GTPases, Cdc42p and Rho1p, are localized to the yeast vacuole where they regulate membrane fusion. Here, we define a method to directly examine vacuole membrane Cdc42p and Rho1p activation based on their affinity to probes derived from effectors. Cdc42p and Rho1p showed unique temporal activation which aligned with distinct subreactions of in vitro vacuole fusion. Cdc42p was rapidly activated in an ATP-independent manner while Rho1p activation was kinetically slower and required ATP. Inhibitors that are known to block vacuole membrane fusion were examined for their effect on Cdc42p and Rho1p activation. Rdi1p, which inhibits the dissociation of GDP from Rho proteins, blocked both Cdc42p and Rho1p activation. Ligands of PI(4,5)P 2 specifically inhibited Rho1p activation while pre-incubation with U73122, which targets Plc1p function, increased Rho1p activation. These results define unique activation mechanisms for Cdc42p and Rho1p, which may be linked to the vacuole membrane fusion mechanism.

  18. Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects

    Science.gov (United States)

    Espinha, Gisele; Osaki, Juliana Harumi; Costa, Erico Tosoni; Forti, Fabio Luis

    2016-01-01

    Ultraviolet radiation is the main cause of DNA damage to melanocytes and development of melanoma, one of the most lethal human cancers, which leads to metastasis due to uncontrolled cell proliferation and migration. These phenotypes are mediated by RhoA, a GTPase overexpressed or overactivated in highly aggressive metastatic tumors that plays regulatory roles in cell cycle progression and cytoskeleton remodeling. This work explores whether the effects of UV on DNA damage, motility, proliferation, and survival of human metastatic melanoma cells are mediated by the RhoA pathway. Mutant cells expressing dominant-negative (MeWo-RhoA-N19) or constitutively active RhoA (MeWo-RhoA-V14) were generated and subjected to UV radiation. A slight reduction in migration and invasion was observed in MeWo and MeWo-RhoA-V14 cells but not in MeWo-RhoA-N19 cells, which presented inefficient motility and invasiveness associated with stress fibers fragmentation. Proliferation and survival of RhoA-deficient cells were drastically reduced by UV compared to cells displaying normal or high RhoA activity, suggesting increased sensitivity to UV. Loss of RhoA activity also caused less efficient DNA repair, with elevated levels of DNA lesions such as strand breaks and cyclobutane pyrimidine dimers (CPDs). Thus, RhoA mediates genomic stability and represents a potential target for sensitizing metastatic tumors to genotoxic agents. PMID:26823948

  19. Local spin dynamics at low temperature in the slowly relaxing molecular chain [Dy(hfac)3(NIT(C6H4OPh))]: A μ{sup +} spin relaxation study

    Energy Technology Data Exchange (ETDEWEB)

    Arosio, Paolo, E-mail: paolo.arosio@guest.unimi.it; Orsini, Francesco [Department of Physics, Università degli Studi di Milano, and INSTM, Milano (Italy); Corti, Maurizio [Department of Physics, Università degli Studi di Pavia and INSTM, Pavia (Italy); Mariani, Manuel [Department of Physics and Astronomy, Università degli Studi di Bologna, Bologna (Italy); Bogani, Lapo [Physikalisches Institut, Universität Stuttgart, Stuttgart (Germany); Caneschi, Andrea [INSTM and Department of Chemistry, University of Florence, Firenze (Italy); Lago, Jorge [Departamento de Quimica Inorganica, Universidad del Pais Vasco, Bilbao (Spain); Lascialfari, Alessandro [Department of Physics, Università degli Studi di Milano, and INSTM, Milano (Italy); Centro S3, Istituto Nanoscienze - CNR, Modena (Italy)

    2015-05-07

    The spin dynamics of the molecular magnetic chain [Dy(hfac){sub 3}(NIT(C{sub 6}H{sub 4}OPh))] were investigated by means of the Muon Spin Relaxation (μ{sup +}SR) technique. This system consists of a magnetic lattice of alternating Dy(III) ions and radical spins, and exhibits single-chain-magnet behavior. The magnetic properties of [Dy(hfac){sub 3}(NIT(C{sub 6}H{sub 4}OPh))] have been studied by measuring the magnetization vs. temperature at different applied magnetic fields (H = 5, 3500, and 16500 Oe) and by performing μ{sup +}SR experiments vs. temperature in zero field and in a longitudinal applied magnetic field H = 3500 Oe. The muon asymmetry P(t) was fitted by the sum of three components, two stretched-exponential decays with fast and intermediate relaxation times, and a third slow exponential decay. The temperature dependence of the spin dynamics has been determined by analyzing the muon longitudinal relaxation rate λ{sub interm}(T), associated with the intermediate relaxing component. The experimental λ{sub interm}(T) data were fitted with a corrected phenomenological Bloembergen-Purcell-Pound law by using a distribution of thermally activated correlation times, which average to τ = τ{sub 0} exp(Δ/k{sub B}T), corresponding to a distribution of energy barriers Δ. The correlation times can be associated with the spin freezing that occurs when the system condenses in the ground state.

  20. RhoB protects human keratinocytes from UVB-induced apoptosis through epidermal growth factor receptor signaling.

    Science.gov (United States)

    Canguilhem, Bruno; Pradines, Anne; Baudouin, Caroline; Boby, Céline; Lajoie-Mazenc, Isabelle; Charveron, Marie; Favre, Gilles

    2005-12-30

    Exposure of the skin to UVB light results in the formation of DNA photolesions that can give rise to cell death, mutations, and the onset of carcinogenic events. Specific proteins are activated by UVB and then trigger signal transduction pathways that lead to cellular responses. An alteration of these signaling molecules is thought to be a fundamental event in tumor promotion by UVB irradiation. RhoB, encoding a small GTPase has been identified as a DNA damage-inducible gene. RhoB is involved in epidermal growth factor (EGF) receptor trafficking, cytoskeletal organization, cell transformation, and survival. We have analyzed the regulation of RhoB and elucidated its role in the cellular response of HaCaT keratinocytes to relevant environmental UVB irradiation. We report here that the activated GTP-bound form of RhoB is increased rapidly within 5 min of exposure to UVB, and then RhoB protein levels increased concomitantly with EGF receptor (EGFR) activation. Inhibition of UVB-induced EGFR activation prevents RhoB protein expression and AKT phosphorylation but not the early activation of RhoB. Blocking UVB-induced RhoB expression with specific small interfering RNAs inhibits AKT and glycogen synthase kinase-3beta phosphorylation through inhibition of EGFR expression. Moreover, down-regulation of RhoB potentiates UVB-induced cell apoptosis. In contrast, RhoB overexpression protects keratinocytes against UVB-induced apoptosis. These results indicated that RhoB is regulated upon UVB exposure by a two-step process consisting of an early EGFR-independent RhoB activation followed by an EGFR-dependent induction of RhoB expression. Moreover, we have demonstrated that RhoB is essential in regulating keratinocyte cell survival after UVB exposure, suggesting its potential role in photocarcinogenesis.

  1. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2010-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  2. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2008-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Measurement of the CP asymmetry and branching fraction of B0-->rho0K0.

    Science.gov (United States)

    Aubert, B; Barate, R; Bona, M; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Gill, M S; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Mir, L M; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; del Amo Sanchez, P; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Morgan, S E; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Sherwood, D J; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Best, D S; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Mommsen, R K; Roethel, W; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; Hadavand, H K; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Dvoretskii, A; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Ryd, A; Samuel, A; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Petzold, A; Spaan, B; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Grenier, P; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Capra, R; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Nash, J A; Nikolich, M B; Panduro Vazquez, W; Behera, P K; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gritsan, A V; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Le Diberder, F; Lepeltier, V; Lutz, A M; Oyanguren, A; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Stocchi, A; Wang, W F; Wormser, G; Cheng, C H; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; Di Lodovico, F; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Ricciardi, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; Naisbit, M T; Williams, J C; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Saremi, S; Staengle, H; Cowan, R; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M; Raven, G; Snoek, H L; Jessop, C P; Losecco, J M; Allmendinger, T; Benelli, G; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Rahimi, A M; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Benayoun, M; Chauveau, J; Briand, H; David, P

    2007-02-02

    We present a measurement of the branching fraction and time-dependent CP asymmetry of B(0)-->rho0K0. The results are obtained from a data sample of 227x10(6) Upsilon(4S)-->BB decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at Stanford Linear Accelerator Center. From a time-dependent maximum likelihood fit yielding 111+/-19 signal events, we find B(B(0)-->rho0K0)=(4.9+/-0.8+/-0.9)x10(-6), where the first error is statistical and the second systematic. We report the measurement of the CP parameters S(rho)(0)K(0)S=0.20+/-0.52+/-0.24 and C(rho)(0)K(0)S=0.64+/-0.41+/-0.20.

  8. Exclusive rho^0 electroproduction on the proton at CLAS

    Energy Technology Data Exchange (ETDEWEB)

    Morrow, Steven; Guidal, Michel; Garcon, Michel; Laget, Jean; Smith, Elton; Adams, Gary; Adhikari, Krishna; Aghasyan, Mher; Amaryan, Moscov; Amaryan, Moskov; Anghinolfi, Marco; Asryan, G.; Audit, Gerard; Avagyan, Harutyun; Bagdasaryan, H.; Baillie, Nathan; Ball, J.P.; Ball, Jacques; Baltzell, Nathan; Barrow, Steve; Battaglieri, Marco; Bedlinskiy, Ivan; Bektasoglu, Mehmet; Bellis, Matthew; Benmouna, Nawal; Berman, Barry; Biselli, Angela; Blaszczyk, Lukasz; Bonner, Billy; Bookwalter, Craig; Bouchigny, Sylvain; Boyarinov, Sergey; Bradford, Robert; Branford, Derek; Briscoe, William; Brooks, William; Bultmann, S.; Bueltmann, Stephen; Burkert, Volker; Butuceanu, Cornel; Calarco, John; Careccia, Sharon; Carman, Daniel; Carnahan, Bryan; Casey, Liam; Cazes, Antoine; Chen, Shifeng; Cheng, Lu; Cole, Philip; Collins, Patrick; Coltharp, Philip; Cords, Dieter; Corvisiero, Pietro; Crabb, Donald; Crannell, Hall; Crede, Volker; Cummings, John; Dale, Daniel; Dashyan, Natalya; De Masi, Rita; De Vita, Raffaella; De Sanctis, Enzo; Degtiarenko, Pavel; Denizli, Haluk; Dennis, Lawrence; Deur, Alexandre; Dhamija, Seema; Dharmawardane, Kahanawita; Dhuga, Kalvir; Dickson, Richard; Didelez, Jean-Pierre; Djalali, Chaden; Dodge, Gail; Doughty, David; Dugger, Michael; Dytman, Steven; Dzyubak, Oleksandr; Egiyan, Hovanes; Egiyan, Kim; Elfassi, Lamiaa; Elouadrhiri, Latifa; Eugenio, Paul; Fatemi, Renee; Fedotov, Gleb; Fersch, Robert; Feuerbach, Robert; Forest, Tony; Fradi, Ahmed; Gavalian, Gagik; Gevorgyan, Nerses; Gilfoyle, Gerard; Giovanetti, Kevin; Girod, Francois-Xavier; Goetz, John; Gohn, Wesley; Gordon, Christopher; Gothe, Ralf; Graham, Lewis; Griffioen, Keith; Guillo, Matthieu; Guler, Nevzat; Guo, Lei; Gyurjyan, Vardan; Hadjidakis, Cynthia; Hafidi, Kawtar; Hakobyan, Hayk; Hanretty, Charles; Hardie, John; Hassall, Neil; Heddle, David; Hersman, F.; Hicks, Kenneth; Hleiqawi, Ishaq; Holtrop, Maurik; Hourany, E.; Hyde, Charles; Ilieva, Yordanka; Ireland, David; Ishkhanov, Boris; Isupov, Evgeny; Ito, Mark; Jenkins, David; Jo, Hyon-Suk; Johnstone, John; Joo, Kyungseon; Juengst, Henry; Kalantarians, Narbe; Keller, Dustin; Kellie, James; Khandaker, Mahbubul; Khetarpal, Puneet; Kim, Wooyoung; Klein, Andreas; Klein, Franz; Klimenko, Alexei; Kossov, Mikhail; Kramer, Laird; Kubarovsky, Valery; Kuhn, Joachim; Kuhn, Sebastian; Kuleshov, Sergey; Kuznetsov, Viacheslav; Lachniet, Jeff; Langheinrich, Jorn; Lawrence, Dave; Li, Ji; Livingston, Kenneth; Lu, Haiyun; MacCormick, Marion; Marchand, Claude; Markov, Nikolai; Mattione, Paul; McAleer, Simeon; McCracken, Michael; McKinnon, Bryan; McNabb, John; Mecking, Bernhard; Mehrabyan, Surik; Melone, Joseph; Mestayer, Mac; Meyer, Curtis; Mibe, Tsutomu; Mikhaylov, Konstantin; Minehart, Ralph; Mirazita, Marco; Miskimen, Rory; Mokeev, Viktor; Morand, Ludyvine; Moreno, Brahim; Moriya, Kei; Moteabbed, Maryam; Mueller, James; Munevar Espitia, Edwin; Mutchler, Gordon; Nadel-Turonski, Pawel; Nasseripour, Rakhsha; Niccolai, Silvia; Niculescu, Gabriel; Niculescu, Maria-Ioana; Niczyporuk, Bogdan; Niroula, Megh; Niyazov, Rustam; Nozar, Mina; O' Rielly, Grant; Osipenko, Mikhail; Ostrovidov, Alexander; Park, Kijun; Park, Sungkyun; Pasyuk, Evgueni; Paterson, Craig; Pereira, S.Anefalos; Philips, Sasha; Pierce, Joshua; Pivnyuk, Nikolay; Pocanic, Dinko; Pogorelko, Oleg; Polli, Ermanno; Popa, Iulian; Pozdnyakov, Sergey; Preedom, Barry; Price, John; Procureur, Sebastien; Prok, Yelena; Protopopescu, Dan; Qin, Liming; Raue, Brian; Riccardi, Gregory; Ricco, Giovanni; Ripani, Marco; Ritchie, Barry; Rosner, Guenther; Rossi, Patrizia; Rubin, Philip; Sabatie, Franck; Saini, Mukesh; Salamanca, Julian; Salgado, Carlos; Santoro, Joseph; Sapunenko, Vladimir; Schott, Diane; Schumacher, Reinhard; Serov, Vladimir; Sharabian, Youri; Sharov, Dmitri; Shvedunov, Nikolay; Skabelin, Alexander; Smith, Lee; Sober, Daniel; Sokhan, Daria; Stavinskiy, Aleksey; Stepanyan, Samuel; Stepanyan, Stepan; Stokes, Burnham; Stoler, Paul; Strakovski, Igor; Strauch, Steffen; Taiuti, Mauro

    2009-01-01

    The $e p\\to e^\\prime p \\rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply in

  9. Rho kinase inhibitors block melanoma cell migration and inhibit metastasis.

    Science.gov (United States)

    Sadok, Amine; McCarthy, Afshan; Caldwell, John; Collins, Ian; Garrett, Michelle D; Yeo, Maggie; Hooper, Steven; Sahai, Erik; Kuemper, Sandra; Mardakheh, Faraz K; Marshall, Christopher J

    2015-06-01

    There is an urgent need to identify new therapeutic opportunities for metastatic melanoma. Fragment-based screening has led to the discovery of orally available, ATP-competitive AKT kinase inhibitors, AT13148 and CCT129254. These compounds also inhibit the Rho-kinases ROCK 1 and ROCK 2 and we show they potently inhibit ROCK activity in melanoma cells in culture and in vivo. Treatment of melanoma cells with CCT129254 or AT13148 dramatically reduces cell invasion, impairing both "amoeboid-like" and mesenchymal-like modes of invasion in culture. Intravital imaging shows that CCT129254 or AT13148 treatment reduces the motility of melanoma cells in vivo. CCT129254 inhibits melanoma metastasis when administered 2 days after orthotopic intradermal injection of the cells, or when treatment starts after metastases have arisen. Mechanistically, our data suggest that inhibition of ROCK reduces the ability of melanoma cells to efficiently colonize the lungs. These results suggest that these novel inhibitors of ROCK may be beneficial in the treatment of metastasis. ©2015 American Association for Cancer Research.

  10. Rho kinase regulates fragmentation and phagocytosis of apoptotic cells

    International Nuclear Information System (INIS)

    Orlando, Kelly A.; Stone, Nicole L.; Pittman, Randall N.

    2006-01-01

    During the execution phase of apoptosis, a cell undergoes cytoplasmic and nuclear changes that prepare it for death and phagocytosis. The end-point of the execution phase is condensation into a single apoptotic body or fragmentation into multiple apoptotic bodies. Fragmentation is thought to facilitate phagocytosis; however, mechanisms regulating fragmentation are unknown. An isoform of Rho kinase, ROCK-I, drives membrane blebbing through its activation of actin-myosin contraction; this raises the possibility that ROCK-I may regulate other execution phase events, such as cellular fragmentation. Here, we show that COS-7 cells fragment into a number of small apoptotic bodies during apoptosis; treating with ROCK inhibitors (Y-27632 or H-1152) prevents fragmentation. Latrunculin B and blebbistatin, drugs that interfere with actin-myosin contraction, also inhibit fragmentation. During apoptosis, ROCK-I is cleaved and activated by caspases, while ROCK-II is not activated, but rather translocates to a cytoskeletal fraction. siRNA knock-down of ROCK-I but not ROCK-II inhibits fragmentation of dying cells, consistent with ROCK-I being required for apoptotic fragmentation. Finally, cells dying in the presence of the ROCK inhibitor Y-27632 are not efficiently phagocytized. These data show that ROCK plays an essential role in fragmentation and phagocytosis of apoptotic cells

  11. 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.

  12. 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 < 0.001), 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. 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

  14. 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.

  15. The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

    Science.gov (United States)

    2016-04-01

    significant impact on expenditures Nothing to report. 11 Significant changes in use or care of human subjects, vertebrate animals, biohazards, and...cancers (4,5), for which the current standard of care is limited to conventional cytotoxic chemotherapy (6). Rho family small GTPases (e.g., RhoA...weight GTPase activity in endothelial cell cultures. Methods Enzymol 2008;443:285-98. 28. Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A

  16. Focal Adhesion Kinase regulates cell-cell contact formation in epithelial cells via modulation of Rho

    International Nuclear Information System (INIS)

    Playford, Martin P.; Vadali, Kavita; Cai Xinming; Burridge, Keith; Schaller, Michael D.

    2008-01-01

    Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a key role in cellular processes such as cell adhesion, migration, proliferation and survival. Recent studies have also implicated FAK in the regulation of cell-cell adhesion. Here, evidence is presented showing that siRNA-mediated suppression of FAK levels in NBT-II cells and expression of dominant negative mutants of FAK caused loss of epithelial cell morphology and inhibited the formation of cell-cell adhesions. Rac and Rho have been implicated in the regulation of cell-cell adhesions and can be regulated by FAK signaling. Expression of active Rac or Rho in NBT-II cells disrupted formation of cell-cell contacts, thus promoting a phenotype similar to FAK-depleted cells. The loss of intercellular contacts in FAK-depleted cells is prevented upon expression of a dominant negative Rho mutant, but not a dominant negative Rac mutant. Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This suggests that FAK regulates cell-cell contact formation by regulation of Rho

  17. Ratios of helicity amplitudes for exclusive {rho}{sup 0} electroproduction

    Energy Technology Data Exchange (ETDEWEB)

    Airapetian, A. [Giessen Univ. (Germany). Physikalisches Inst.; Michigan Univ., Ann Arbor, MI (United States). Randall Lab. of Physics; Akopov, N. [Yerevan Physics Institute (Armenia); Akopov, Z. [DESY, Hamburg (DE)] (and others)

    2010-12-15

    Exclusive {rho}{sup 0}-meson electroproduction is studied in the HERMES experiment, using a 27.6 GeV longitudinally polarized electron/positron beam and unpolarized hydrogen and deuterium targets in the kinematic region 0.5 GeV{sup 2}rho}{sub T}), T{sub 01}({gamma}{sub T}{sup *} {yields} {rho}{sub L}), T{sub 10}({gamma}{sub L}{sup *} {yields} {rho}{sub T}), and T{sub 1-1}({gamma}{sub -T}{sup *} {yields} {rho}{sub T}) to T{sub 00} ({gamma}{sub L}{sup *} {yields} {rho}{sub L}) are extracted from the data. For the unnatural-parity-exchange amplitude U{sub 11}, the ratio vertical stroke U{sub 11}/T{sub 00} vertical stroke is obtained. The Q{sup 2} and t{sup '} dependences of these ratios are presented and compared with perturbative QCD predictions. (orig.)

  18. EspM2 is a RhoA guanine nucleotide exchange factor.

    Science.gov (United States)

    Arbeloa, Ana; Garnett, James; Lillington, James; Bulgin, Richard R; Berger, Cedric N; Lea, Susan M; Matthews, Steve; Frankel, Gad

    2010-05-01

    We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. Substitution of Q124, located within the catalytic loop of EspM2, with alanine, greatly attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce stress fibres upon ectopic expression. These results suggest that binding of SifA to RhoA does not trigger nucleotide exchange while EspM2 is a unique Rho GTPase GEF.

  19. Ratios of helicity amplitudes for exclusive {rho}{sup 0} electroproduction

    Energy Technology Data Exchange (ETDEWEB)

    Airapetian, A. [Univ. Giessen, Physikalisches Inst. (Germany); Univ. of Michigan, Randall Lab. of Physics, Ann Arbor, MI (United States); Akopov, N.; Avakian, R.; Avetissian, A.; Elbakian, G.; Gharibyan, V.; Karyan, G.; Marukyan, H.; Movsisyan, A.; Taroian, S. [Yerevan Physics Inst. (Armenia); Akopov, Z.; Avetisyan, E.; Borissov, A.; Deconinck, W.; Hartig, M.; Holler, Y.; Rostomyan, A.; Schueler, K.P.; Zihlmann, B. [DESY, Hamburg (Germany); Aschenauer, E.C.; Fabbri, R.; Gabbert, D.; Golembiovskaya, M.; Hillenbrand, A.; Hristova, I.; Lu, X.G.; Negodaev, M.; Nowak, W.D.; Riedl, C. [DESY, Zeuthen (Germany); Augustyniak, W.; Marianski, B.; Trzcinski, A.; Zupranski, P. [Andrzej Soltan Inst. for Nuclear Studies, Warsaw (Poland); Belostotski, S.; Kisselev, A.; Kravchenko, P.; Manaenkov, S.I.; Naryshkin, Y.; Veretennikov, D.; Vikhrov, V. [St. Petersburg Nuclear Physics Inst., Gatchina, Leningrad region (Russian Federation); Bianchi, N.; Capitani, G.P.; De Sanctis, E.; Di Nezza, P.; Fantoni, A.; Hadjidakis, C.; Hasch, D.; Muccifora, V.; Reolon, A.R. [Lab. Nazionali di Frascati, Istituto Nazionale di Fisica Nucleare (Italy); Blok, H.P. [National Inst. for Subatomic Physics, Amsterdam (Netherlands); VU Univ., Dept. of Physics and Astronomy, Amsterdam (Netherlands); Bowles, J.; Burns, J.; Hill, G.; Hoek, M.; Kaiser, R.; Lehmann, I.; Mahon, D.; Murray, M.; Rosner, G.; Seitz, B. [Univ. of Glasgow (United Kingdom); Bryzgalov, V.; Gapienko, G.; Gapienko, V.; Ivanilov, A.; Korotkov, V.; Salomatin, Y. [Inst. for High Energy Physics, Protvino, Moscow region (Russian Federation); Capiluppi, M.; Ciullo, G.; Contalbrigo, M.; Dalpiaz, P.F.; Lenisa, P.; Pappalardo, L.L.; Stancari, M.; Statera, M. [Univ. di Ferrara, Istituto Nazionale di Fisica Nucleare, Sezione di Ferrara (Italy); Dipt. di Fisica, Ferrara (Italy); Cisbani, E.; Frullani, S.; Garibaldi, F.; Manfre, L. [Istituto Nazionale di Fisica Nucleare, Roma (Italy); Ist. Superiore di Sanita, Roma (Italy)] [and others

    2011-04-15

    Exclusive {rho}{sup 0}-meson electroproduction is studied in the HERMES experiment, using a 27.6 GeV longitudinally polarized electron/positron beam and unpolarized hydrogen and deuterium targets in the kinematic region 0.5 GeV{sup 2}rho}{sub T}), T{sub 01} ({gamma}{sup *}{sub T} {yields}{rho}{sub L}), T{sub 10} ({gamma}{sup *}{sub L} {yields}{rho}{sub T}), and T{sub 1-1} ({gamma}{sup *}{sub -T}{yields}{rho}{sub T}) to T{sub 00} ({gamma}{sup *}{sub L}{yields}{rho}{sub L}) are extracted from the data. For the unnatural-parity-exchange amplitude U{sub 11}, the ratio vertical stroke U{sub 11}/T{sub 00} vertical stroke is obtained. The Q{sup 2} and t' dependences of these ratios are presented and compared with perturbative QCD predictions. (orig.)

  20. 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

  1. Ice Cores

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Records of past temperature, precipitation, atmospheric trace gases, and other aspects of climate and environment derived from ice cores drilled on glaciers and ice...

  2. Core BPEL

    DEFF Research Database (Denmark)

    Hallwyl, Tim; Højsgaard, Espen

    extensions. Combined with the fact that the language definition does not provide a formal semantics, it is an arduous task to work formally with the language (e.g. to give an implementation). In this paper we identify a core subset of the language, called Core BPEL, which has fewer and simpler constructs......, does not allow omissions, and does not contain ignorable elements. We do so by identifying syntactic sugar, including default values, and ignorable elements in WS-BPEL. The analysis results in a translation from the full language to the core subset. Thus, we reduce the effort needed for working...... formally with WS-BPEL, as one, without loss of generality, need only consider the much simpler Core BPEL. This report may also be viewed as an addendum to the WS-BPEL standard specification, which clarifies the WS-BPEL syntax and presents the essential elements of the language in a more concise way...

  3. The structure of protostellar dense cores: a millimeter continuum study

    International Nuclear Information System (INIS)

    Motte, Frederique

    1998-01-01

    A comprehensive theoretical scenario explains low-mass star formation and describes the gravitational collapse of an isolated 'ideal' dense core. The major aim of this thesis is to check the standard model predictions on the structure of protostellar dense cores (or envelopes). The earliest stages of star formation remain poorly known because the protostars are still deeply embedded in massive, opaque circumstellar cocoons. On the one hand, sensitive bolometer arrays very recently allow us to measure the millimeter continuum emission arising from dense cores. Such observations are a powerful tool to constrain the density structure of proto-stellar dense cores (on large length scale). In particular, we studied the structure of isolated proto-stellar envelopes in Taurus and protostars in the ρ Ophiuchi cluster. In order to accurately derive their envelope density power law, we simulated the observation of several envelope models. Then we show that most of the Taurus protostars present a density structure consistent with the standard model predictions. In contrast, dense cores in ρ Ophiuchi main cloud are highly fragmented and protostellar envelope have finite size. Moreover fragmentation appears to be essential in determining the final stellar mass of ρ Oph forming stars. In clusters, fragmentation may thus be at the origin of the stellar initial mass function (IMF). On the other hand, our interferometric millimeter continuum observations are tracing (with higher angular resolution) the inner part of protostellar envelopes. Our study show that disks during protostellar stages are not yet massive and thus do not perturb the analysis of envelope density structure. (author) [fr

  4. Role of Wasp and the small GTPases RhoA, RhoB, and Cdc42 during capacitation and acrosome reaction in spermatozoa of English guinea pigs.

    Science.gov (United States)

    Delgado-Buenrostro, Norma L; Mújica, Adela; Chiquete-Felix, Natalia; Déciga-Alcaraz, Alejandro; Medina-Reyes, Estefany I; Uribe-Carvajal, Salvador; Chirino, Yolanda I

    2016-10-01

    Cytoskeleton remodeling is necessary for capacitation and the acrosome reaction in spermatozoa. F-actin is located in the acrosome and equatorial region during capacitation, but is relocated in the post-acrosomal region during the acrosome reaction in spermatozoa from bull, rat, mice, and guinea pig. Actin polymerization and relocalization are generally regulated by small GTPases that activate Wasp protein, which coordinates with Arp2/3, profilin I, and profilin II to complete cytoskeletal remodeling. This sequence of events is not completely described in spermatozoa, though. Therefore, the aim of this study was to determine if Wasp interacts with small GTPases (RhoA, RhoB, and Cdc42) and proteins (Arp2/3, profilin I, and profilin II) that co-localize with F-actin during capacitation and the acrosome reaction in English guinea pig spermatozoa obtained from the vas deferens. The spermatozoa were capacitated in calcium-free medium, incubated with an activator or an inhibitor of GTPases, and then induced to acrosome react using calcium. The distribution patterns of F-actin were compared to the patterns of Wasp and its putative interaction partners: Wasp and RhoB, but not RhoA or Cdc42, localization overlap with F-actin during capacitation and the acrosome reaction. Activation of small GTPases localized RhoB to the post-acrosomal region whereas their inhibition prevented acrosome exocytosis. Arp2/3 and profilin II appear to interact with Wasp in the post-acrosomal region and flagellum, while profilin I and Wasp could be found in the equatorial region. Thus, Wasp and F-actin distribution overlap during capacitation and acrosome reaction, and small GTPases play an important role in cytoskeleton remodeling during these processes in spermatozoa. Mol. Reprod. Dev. 83: 927-937, 2016 © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. 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

  6. 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.

  7. RhoA/rock signaling mediates peroxynitrite-induced functional impairment of Rat coronary vessels.

    Science.gov (United States)

    Sun, Zhijun; Wu, Xing; Li, Weiping; Peng, Hui; Shen, Xuhua; Ma, Lu; Liu, Huirong; Li, Hongwei

    2016-10-11

    Diabetes-induced vascular dysfunction may arise from reduced nitric oxide (NO) availability, following interaction with superoxide to form peroxynitrite. Peroxynitrite can induce formation of 3-nitrotyrosine-modified proteins. RhoA/ROCK signaling is also involved in diabetes-induced vascular dysfunction. The study aimed to investigate possible links between Rho/ROCK signaling, hyperglycemia, and peroxynitrite in small coronary arteries. Rat small coronary arteries were exposed to normal (NG; 5.5 mM) or high (HG; 23 mM) D-glucose. Vascular ring constriction to 3 mM 4-aminopyridine and dilation to 1 μM forskolin were measured. Protein expression (immunohistochemistry and western blot), mRNA expression (real-time PCR), and protein activity (luminescence-based G-LISA and kinase activity spectroscopy assays) of RhoA, ROCK1, and ROCK2 were determined. Vascular ring constriction and dilation were smaller in the HG group than in the NG group (P Peroxynitrite impaired vascular ring constriction/dilation; this was partially reversed by inhibition of RhoA or ROCK. Protein and mRNA expressions of RhoA, ROCK1, and ROCK2 were higher under HG than NG (P Peroxynitrite also enhanced RhoA, ROCK1, and ROCK2 activity; these actions were partially inhibited by 100 μM urate (peroxynitrite scavenger). Exogenous peroxynitrite had no effect on the expression of the voltage-dependent K + channels 1.2 and 1.5. Peroxynitrite-induced coronary vascular dysfunction may be mediated, at least in part, through increased expressions and activities of RhoA, ROCK1, and ROCK2.

  8. SCISSOR?Spinal Cord Injury Study on Small molecule-derived Rho inhibition: a clinical study protocol

    OpenAIRE

    Kopp, Marcel A; Liebscher, Thomas; Watzlawick, Ralf; Martus, Peter; Laufer, Stefan; Blex, Christian; Schindler, Ralf; Jungehulsing, Gerhard J; Kn?ppel, Sven; Kreutztr?ger, Martin; Ekkernkamp, Axel; Dirnagl, Ulrich; Strittmatter, Stephen M; Niedeggen, Andreas; Schwab, Jan M

    2016-01-01

    Introduction The approved analgesic and anti-inflammatory drugs ibuprofen and indometacin block the small GTPase RhoA, a key enzyme that impedes axonal sprouting after axonal damage. Inhibition of the Rho pathway in a central nervous system-effective manner requires higher dosages compared with orthodox cyclooxygenase-blocking effects. Preclinical studies on spinal cord injury (SCI) imply improved motor recovery after ibuprofen/indometacin-mediated Rho inhibition. This has been reassessed by ...

  9. RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription

    OpenAIRE

    Gerald, Damien; Adini, Irit; Shechter, Sharon; Perruzzi, Carole; Varnau, Joseph; Hopkins, Benjamin; Kazerounian, Shiva; Kurschat, Peter; Blachon, Stephanie; Khedkar, Santosh; Bagchi, Mandrita; Sherris, David; Prendergast, George C.; Klagsbrun, Michael; Stuhlmann, Heidi

    2013-01-01

    Mechanisms governing the distinct temporal dynamics that characterize post-natal angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses to growth factors, genotoxic stress and neoplastic transformation. Here we show, using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in the ischaemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances...

  10. 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.

  11. Megakaryocyte-specific RhoA deficiency causes macrothrombocytopenia and defective platelet activation in hemostasis and thrombosis

    DEFF Research Database (Denmark)

    Pleines, Irina; Hagedorn, Ina; Gupta, Shuchi

    2011-01-01

    -type controls. The mutant cells displayed an altered shape but only a moderately reduced life span. Shape change of RhoA-deficient platelets in response to G(13)-coupled agonists was abolished, and it was impaired in response to G(q) stimulation. Similarly, RhoA was required for efficient secretion...... of a and dense granules downstream of G(13) and G(q). Furthermore, RhoA was essential for integrin-mediated clot retraction but not for actomyosin rearrangements and spreading of activated platelets on fibrinogen. In vivo, RhoA deficiency resulted in markedly prolonged tail bleeding times but also significant...

  12. 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.

  13. Coring apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Mount, W.W.

    1967-11-14

    This invention relates to coring equipment and has special reference to such as are intended to be driven or otherwise inserted into sand or other loose formations to obtain a true sample of the formation. The device includes a plurality of elongated angular members positioned to form an elongated core receptacle between them. A plurality of links are each pivotally mounted at each end on an adjacent member to hold the members in spaced-apart relation in one position. The receptable is driven into the sand, and the members are moved toward one another when they are longitudinally moved with respect to one another to close the receptable. (3 claims)

  14. 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

  15. Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Nicolai Skovbjerg Arildsen

    2017-05-01

    genetically heterogeneous, but harbor frequent alterations in chromatin remodeling genes. Overexpression of TFAP2A and ERBB2 was observed on the mRNA level in relation to other ovarian cancer subtypes. However, overexpression of ERBB2 was not reflected by HER2 amplification or protein overexpression in the OCCC validation cohort. In addition, Rho GTPase-dependent actin organization may also play a role in OCCC pathogenesis and warrants further investigation. The distinct biological features of OCCC discovered here may provide a basis for novel targeted treatment strategies.

  16. Q2 dependence of nuclear transparency for exclusive rho0 production.

    Science.gov (United States)

    Airapetian, A; Akopov, N; Akopov, Z; Amarian, M; Ammosov, V V; Andrus, A; Aschenauer, E C; Augustyniak, W; Avakian, R; Avetissian, A; Avetissian, E; Bailey, P; Baturin, V; Baumgarten, C; Beckmann, M; Belostotski, S; Bernreuther, S; Bianchi, N; Blok, H P; Böttcher, H; Borissov, A; Bouwhuis, M; Brack, J; Brüll, A; Brunn, I; Capitani, G P; Chiang, H C; Ciullo, G; Contalbrigo, M; Court, G R; Dalpiaz, P F; De Leo, R; De Nardo, L; De Sanctis, E; Devitsin, E; Di Nezza, P; Düren, M; Ehrenfried, M; Elalaoui-Moulay, A; Elbakian, G; Ellinghaus, F; Elschenbroich, U; Ely, J; Fabbri, R; Fantoni, A; Fechtchenko, A; Felawka, L; Fox, B; Franz, J; Frullani, S; Gärber, Y; Gapienko, G; Gapienko, V; Garibaldi, F; Garutti, E; Gaskell, D; Gavrilov, G; Gharibyan, V; Graw, G; Grebeniouk, O; Greeniaus, L G; Haeberli, W; Hafidi, K; Hartig, M; Hasch, D; Heesbeen, D; Henoch, M; Hertenberger, R; Hesselink, W H A; Hillenbrand, A; Holler, Y; Hommez, B; Iarygin, G; Izotov, A; Jackson, H E; Jgoun, A; Kaiser, R; Kinney, E; Kisselev, A; Königsmann, K; Kolster, H; Kopytin, M; Korotkov, V; Kozlov, V; Krauss, B; Krivokhijine, V G; Lagamba, L; Lapikás, L; Laziev, A; Lenisa, P; Liebing, P; Lindemann, T; Lorenzon, W; Makins, N C R; Marukyan, H; Masoli, F; Menden, F; Mexner, V; Meyners, N; Mikloukho, O; Miller, C A; Miyachi, Y; Muccifora, V; Nagaitsev, A; Nappi, E; Naryshkin, Y; Nass, A; Negodaeva, K; Nowak, W-D; Oganessyan, K; Ohsuga, H; Orlandi, G; Podiatchev, S; Potashov, S; Potterveld, D H; Raithel, M; Reggiani, D; Reimer, P; Reischl, A; Reolon, A R; Rith, K; Rosner, G; Rostomyan, A; Ryckbosch, D; Sanjiev, I; Savin, I; Scarlett, C; Schäfer, A; Schill, C; Schnell, G; Schüler, K P; Schwind, A; Seibert, J; Seitz, B; Shanidze, R; Shibata, T-A; Shutov, V; Simani, M C; Sinram, K; Stancari, M; Statera, M; Steffens, E; Steijger, J J M; Stewart, J; Stösslein, U; Tanaka, H; Taroian, S; Tchuiko, B; Terkulov, A; Tessarin, S; Thomas, E; Tkabladze, A; Trzcinski, A; Tytgat, M; Urciuoli, G M; Van Der Nat, P; Van Der Steenhoven, G; Van De Vyver, R; Vetterli, M C; Vikhrov, V; Vincter, M G; Visser, J; Vogt, M; Volmer, J; Weiskopf, C; Wendland, J; Wilbert, J; Wise, T; Yen, S; Yoneyama, S; Zihlmann, B; Zohrabian, H; Zupranski, P

    2003-02-07

    Exclusive coherent and incoherent electroproduction of the rho(0) meson from 1H and 14N targets has been studied at the HERMES experiment as a function of coherence length (l(c)), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon (-Q2). The ratio of 14N to 1H cross sections per nucleon, called nuclear transparency, was found to increase (decrease) with increasing l(c) for coherent (incoherent) rho(0) electroproduction. For fixed l(c), a rise of nuclear transparency with Q2 is observed for both coherent and incoherent rho(0) production, which is in agreement with theoretical calculations of color transparency.

  17. 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.

  18. 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

    Tissues accommodate defined numbers of dendritic cells (DCs) in highly specific niches where different intrinsic and environmental stimuli control DC life span and numbers. DC homeostasis in tissues is important, because experimental changes in DC numbers influence immunity and tolerance toward...... various immune catastrophes and inflammation. However, the precise molecular mechanisms regulating DC life span and homeostasis are unclear. We report that the GTPase RhoA controls homeostatic proliferation, cytokinesis, survival, and turnover of cDCs. Deletion of RhoA strongly decreased the numbers of CD...... 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....

  19. 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

    The positioning of neurons in the cerebral cortex is of crucial importance for its function as highlighted by the severe consequences of migrational disorders in patients. Here we show that genetic deletion of the small GTPase RhoA in the developing cerebral cortex results in two migrational...... 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......, whereas the converse was not the case. Alterations in the radial glia scaffold are demonstrated to cause these migrational defects through destabilization of both the actin and the microtubules cytoskeleton. These data not only demonstrate that RhoA is largely dispensable for migration in neurons but also...

  20. Rho GTPases and Nox dependent ROS production in skin. Is there a connection?

    DEFF Research Database (Denmark)

    Stanley, Alanna; Hynes, Ailish; Brakebusch, Cord Herbert

    2012-01-01

    Rho GTPases are a family of small GTP binding proteins most commonly known for the regulation of many cellular processes, including actin cytoskeleton re-organisation, cell proliferation, signal transduction and regulation of apoptosis. Additionally, a link between Rho GTPases and reactive oxygen...... cell biological processes, including cell growth, differentiation, migration, angiogenesis, aimed at maintaining tissue homeostasis. Data suggests that skin cells are capable of a regulated ROS production via Nox complexes. Members of the Rho GTPase family have been found to play a central regulatory...... species (ROS) has been shown. In line with the growing interest in the role of ROS in cell biology, the relevance of this connection is becoming increasingly clearer. ROS production is classically associated with oxidative metabolic pathways (e.g. respiratory chain, arachidonic acid). During...

  1. Measurement of the B+- --> rho+- pi0 Branching Fraction and Direct CP Asymmetry

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, B.; Barate, R.; Boutigny, D.; Couderc, F.; Karyotakis, Y.; Lees, J.P.; Poireau, V.; Tisserand, V.; Zghiche, A.; /Annecy, LAPP; Grauges, E.; /Barcelona, IFAE; Palano, A.; Pappagallo, M.; Pompili, A.; /Bari U. /INFN, Bari; Chen, J.C.; Qi, N.D.; Rong, G.; Wang, P.; Zhu, Y.S.; /Beijing, Inst. High Energy Phys.; Eigen, G.; Ofte, I.; Stugu, B.

    2005-06-29

    An improved measurement of the process B{sup {+-}} {yields} {rho}{sup {+-}}{pi}{sup 0} is presented. The data sample of 211 fb{sup -1} comprises 232 million {Upsilon}(4S) {yields} B{bar B} decays collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. The yield and CP asymmetry are calculated using an extended maximum likelihood fitting method. The branching fraction and asymmetry are found to be {Beta}(B{sup {+-}} {yields} {rho}{sup {+-}}{pi}{sup 0}) = [10.0 {+-} 1.4 (Stat.) {+-} 0.9 (Syst.)] x 10{sup -6} and {Alpha}{sub CP}(B{sup {+-}} {yields} {rho}{sup {+-}}{pi}{sup 0}) = -0.01 {+-} 0.13 (Stat.) {+-} 0.02 (Syst.), superseding previous measurements. The statistical significance of the signal is calculated to be 8.7{sigma}.

  2. 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.

  3. 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...

  4. 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.

  5. 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

  6. Search for the Decay B{sup 0} --> K*{sup +}{rho}{sup -}

    Energy Technology Data Exchange (ETDEWEB)

    Aubert, Bernard

    2004-08-16

    The authors present the preliminary result of a search for the decay of B{sup 0} --> K*{sup +}{rho}{sup -}. The data were recorded with the BABAR detector at the PEP-II collider and correspond to 123 million B{bar B} pairs produced in the e{sup +}e{sup -} annihilation through the {Upsilon}(4S) resonance. They obtain an upper limit on the branching fraction of this decay of B(B{sup 0} --> K*{sup +}{rho}{sup -}) < 24 x 10{sup -6} (90% C.L.). All results are preliminary.

  7. 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.

  8. 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.

  9. 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).

  10. RhoA exerts a permissive effect on volume-regulated anion channels in vascular endothelial cells

    DEFF Research Database (Denmark)

    Carton, Iris; Trouet, Dominique; Hermans, Diane

    2002-01-01

    Cell swelling triggers in most cell types an outwardly rectifying anion current, I(Cl,swell), via volume-regulated anion channels (VRACs). We have previously demonstrated in calf pulmonary artery endothelial (CPAE) cells that inhibition of the Rho/Rho kinase/myosin light chain phosphorylation pat...

  11. Quantum numbers of the X state and orbital angular momentum in its rho(0)J/psi decay

    NARCIS (Netherlands)

    Aaij, R.; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Gutierrez, O. Aquines; Archilli, F.; d'Argent, P.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Bel, L. J.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Bettler, M. -O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Birnkraut, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Brett, D.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Campana, P.; Perez, D. Campora; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Akiba, K. Carvalho; Casanova Mohr, R.; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch.; Cavallero, G.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Cheung, S. -F.; Chiapolini, N.; Chrzaszcz, M.; Vidal, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collazuol, G.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Torres, M. Cruz; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Dean, C. -T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Deleage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Ruscio, F.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suarez, A.; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Faerber, C.; Farinelli, C.; Farley, N.; Farry, S.; Fay, R.; Ferguson, D.; Fernandez Albor, V.; Ferrari, F.; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fol, P.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frei, C.; Frosini, M.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Garcia Pardinas, J.; Garofoli, J.; Tico, J. Garra; Garrido, L.; Gascon, D.; Gaspar, C.; Gastaldi, U.; Gauld, R.; Gavardi, L.; Gazzoni, G.; Geraci, A.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianelle, A.; Giani, S.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Goeel, C.; Golubkov, D.; Golutvin, A.; Gotti, C.; Gandara, M. Grabalosa; Graciani Diaz, R.; Cardoso, L. A. Granado; Grauges, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Gruenberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Hernando Morata, J. A.; van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Humair, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kelsey, M.; Kenyon, I. R.; Kenzie, M.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koppenburg, P.; Korolev, M.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J. -P.; Lefevre, R.; Leflat, A.; Lefrancois, J.; Leroy, O.; Lesiak, T.; Leverington, B.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lowdon, P.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Manning, P.; Mapelli, A.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marino, P.; Maerki, R.; Marks, J.; Martellotti, G.; Martinelli, M.; Santos, D. Martinez; Martinez Vidal, F.; Tostes, D. Martins; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurin, B.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Merk, M.; Milanes, D. A.; Minard, M. -N.; Mitzel, D. S.; Rodriguez, J. Molina; Monteil, S.; Morandin, M.; Morawski, P.; Morda, A.; Morello, M. J.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mueller, J.; Mueller, K.; Mueller, V.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen-Mau, C.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Ninci, D.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, C. J. G.; Rodrigues, B. Osorio; Goicochea, J. M. Otalora; Otto, A.; Owen, P.; Oyanguren, A.; Palano, A.; Palombo, F.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parkes, C.; Passaleva, G.; Patel, G. D.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Altarelli, M. Pepe; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petruzzo, M.; Olloqui, E. Picatoste; Pietrzyk, B.; Pilar, T.; Pinci, D.; Pistone, A.; Playfer, S.; Plo Casasus, M.; Poikela, T.; Polci, F.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, E.; Price, J. D.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redi, F.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Molina, V. Rives; Rodrigues, A. B.; Rodrigues, E.; Lopez, J. A. Rodriguez; Perez, P. Rodriguez; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Ruiz Valls, P.; Silva, J. J. Saborido; Sagidova, N.; Sail, P.; Saitta, B.; Guimaraes, V. Salustino; Sanchez Mayordomo, C.; Sedes, B. Sanmartin; Santacesaria, R.; Rios, C. Santamarina; Santimaria, M.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M. -H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Coutinho, R. Silva; Simi, G.; Sirendi, M.; Skidmore, N.; Skillicorn, I.; Skwarnicki, T.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; De Paula, B. Souza; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Sterpka, F.; Stevenson, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Tekampe, T.; Teklishyn, M.; Tellarini, G.; Teubert, F.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Todd, J.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valenti, G.; Vallier, A.; Gomez, R. Vazquez; Regueiro, P. Vazquez; Sierra, C. Vazquez; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Diaz, M. Vieites; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voss, C.; Waldi, R.; Wallace, C.; Wallace, R.; Wandernoth, S.; Ward, D. R.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wiedner, D.; Wilkinson, G.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wyllie, K.; Xie, Y.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhelezov, A.; Zhokhov, A.; Zhong, L.

    2015-01-01

    Angular correlations in B+ -> X(3872)K+ decays, with X(3872) -> rho(0)J/psi, rho(0) -> pi(+)pi(-) and J/psi -> pi(+)pi(-), are used to measure orbital angular momentum contributions and to determine the J(PC) value of the X(3872) meson. The data correspond to an integrated luminosity of 3.0 fb(-1)

  12. 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.

  13. Secretory pathway-dependent localization of the Saccharomyces cerevisiae Rho GTPase-activating protein Rgd1p at growth sites.

    Science.gov (United States)

    Lefèbvre, Fabien; Prouzet-Mauléon, Valérie; Hugues, Michel; Crouzet, Marc; Vieillemard, Aurélie; McCusker, Derek; Thoraval, Didier; Doignon, François

    2012-05-01

    Establishment and maintenance of cell polarity in eukaryotes depends upon the regulation of Rho GTPases. In Saccharomyces cerevisiae, the Rho GTPase activating protein (RhoGAP) Rgd1p stimulates the GTPase activities of Rho3p and Rho4p, which are involved in bud growth and cytokinesis, respectively. Consistent with the distribution of Rho3p and Rho4p, Rgd1p is found mostly in areas of polarized growth during cell cycle progression. Rgd1p was mislocalized in mutants specifically altered for Golgi apparatus-based phosphatidylinositol 4-P [PtdIns(4)P] synthesis and for PtdIns(4,5)P(2) production at the plasma membrane. Analysis of Rgd1p distribution in different membrane-trafficking mutants suggested that Rgd1p was delivered to growth sites via the secretory pathway. Rgd1p may associate with post-Golgi vesicles by binding to PtdIns(4)P and then be transported by secretory vesicles to the plasma membrane. In agreement, we show that Rgd1p coimmunoprecipitated and localized with markers specific to secretory vesicles and cofractionated with a plasma membrane marker. Moreover, in vivo imaging revealed that Rgd1p was transported in an anterograde manner from the mother cell to the daughter cell in a vectoral manner. Our data indicate that secretory vesicles are involved in the delivery of RhoGAP Rgd1p to the bud tip and bud neck.

  14. 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)

  15. 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.

  16. 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.

  17. RhoA Inactivation Prevents Photoreceptor Axon Retraction in an In Vitro Model of Acute Retinal Detachment

    Science.gov (United States)

    Fontainhas, Aurora Maria

    2011-01-01

    Purpose. An early injury response to retinal detachment is disruption of synaptic connectivity between photoreceptors and second-order neurons. Most dramatic is the retraction of rod cell axons and their terminals away from the outer synaptic layer and toward their cell bodies. This study tested whether axonal retraction in detached retina was due to the activation of the small GTPase RhoA and was preventable using RhoA antagonists. Methods. Retinal detachments were created in in vitro preparations of porcine eyecups. RhoA activation was determined with a Rhotekin binding assay. To block axon retraction, drugs were applied to neural retinal explants either before or after detachment from the retinal pigment epithelium. Presynaptic movement was quantified by image analysis of double-labeled retinas examined with confocal microscopy. Results. Active RhoA increases transiently after detachment followed by morphologic evidence of axonal retraction over the next 24 hours. Pretreating the retina with a RhoA antagonist, CT-04, or a Rho kinase inhibitor, Y27632, at multiple concentrations significantly inhibited axonal retraction. Reducing calcium influx through L-type calcium channels with nicardipine also blocked retraction. To create a more plausible therapeutic scenario, drug treatments were delayed and applied after retinal detachment. The Rho kinase inhibitor, but not nicardipine, significantly blocked rod axonal retraction when applied up to 6 hours after detachment. Conclusions. Thus, RhoA and downstream Rho kinase activity constitute part of the mechanism that produces rod axonal retraction in retinal explants. Treatments that manipulate RhoA signaling may promote synaptic stability after retinal detachment. PMID:20861490

  18. 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...

  19. The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface

    DEFF Research Database (Denmark)

    Cappello, Silvia; Attardo, Alessio; Wu, Xunwei

    2006-01-01

    the fundamental difference between these progenitors. Here we show that the conditional deletion of the small Rho-GTPase cdc42 at different stages of neurogenesis in mouse telencephalon results in an immediate increase in basal mitoses. Whereas cdc42-deficient progenitors have normal cell cycle length...

  20. Metastasis of aggressive amoeboid sarcoma cells is dependent on Rho/ROCK/MLC signaling

    Czech Academy of Sciences Publication Activity Database

    Kosla, Jan; Paňková, D.; Plachý, Jiří; Tolde, O.; Bicanova, K.; Dvořák, Michal; Rosel, D.; Brabek, J.

    2013-01-01

    Roč. 11, č. 1 (2013), s. 51 ISSN 1478-811X R&D Projects: GA MŠk(CZ) LC06061 Institutional support: RVO:68378050 Keywords : metastasis * sarcoma * rhoA * ROCK * MLC * amoeboid invasiveness * 3D environment * chi cken model Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.672, year: 2013

  1. 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.

  2. Rho_T Production via W_L Z_L Fusion at Hadronic Colliders

    CERN Document Server

    Azuelos, Georges; Slabospitsky, S R

    1999-01-01

    Multiscale technicolor models predict the existence of high mass resonances at hadron colliders. Although the quark fusion process of production dominates, vector boson fusion offers the advantage of allowing forward jet tagging for background suppression. We calculate here the cross section and differential distributions for rho_T production, in the vector boson fusion channel and evaluate the possibility for observation

  3. 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

    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...

  4. 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.)

  5. 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

  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. Evidence for B{sup 0} --> {rho}{sup 0}K{sup 0}/S

    Energy Technology Data Exchange (ETDEWEB)

    Payne, D

    2004-08-17

    The authors present evidence for the decay B{sup 0} --> {rho}{sup 0}K{sup 0}S. The results are obtained from a data sample of 227 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 maximum-likelihood fit giving a yield of 99{+-}19 events and efficiency estimated from simulation the authors make a preliminary measurement of the branching fraction B{sup 0} --> {rho}{sup 0} K{sup 0} = (5.1 {+-} 1.0 {+-} 1.2) 10{sup -6} where the first error is statistical and the second systematic. The hypothesis of zero signal in the {rho}{sup 0} mass region, 600MeV-930MeV, is excluded at the 6.1sigma level. Allowing a B{sup 0} --> f{sub 0}(600)K{sup 0}s contribution in the fit allows the authors to exclude the hypothesis of zero B{sup -} --> {rho}{sup 0}K{sup 0}s at the 3.5sigma level.

  8. Rho-family GTPase Cdc42 controls migration of Langerhans cells in vivo

    DEFF Research Database (Denmark)

    Luckashenak, Nancy; Wähe, Anna; Breit, Katharina

    2013-01-01

    and contributions of this cell type. To target the migratory properties of DCs, we generated mice lacking the Rho-family GTPase Cdc42 specifically in DCs. In these animals, the initial seeding of the epidermis with LCs is functional, resulting in slightly reduced Langerhans cell numbers. However, Cdc42-deficient...

  9. 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.

  10. 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.)

  11. 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.

  12. 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.

  13. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke

    DEFF Research Database (Denmark)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário

    2017-01-01

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our ...

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. Stabilization of anaphase midzone microtubules is regulated by Rho during cytokinesis in human fibrosarcoma cells.

    Science.gov (United States)

    Kanada, Masamitsu; Nagasaki, Akira; Uyeda, Taro Q P

    2009-10-01

    The dynamics of astral and midzone microtubules (MTs) must be separately regulated during cell division, but the mechanism of selective stabilization of midzone MTs is poorly understood. Here we show that, in HT1080 cells, activation of Rho is required to stabilize midzone MTs, and to maintain the midzone structures after anaphase onset or during cytokinesis. Ect2-depleted cells undergoing conventional cytokinesis (cytokinesis A) or contractile ring-independent cytokinesis (cytokinesis B) formed abnormally thin bundles of midzone MTs. C3-loaded mitotic cells with inactivated Rho showed similar but more severe disorganization of midzone MTs. In addition, the bundles of astral MTs were abnormally abundant along the cell periphery in both Ect2-depleted and C3-loaded mitotic cells. Mitotic kinesin-like protein 1 (MKLP1), a component of the spindle midzone required for bundling of MTs, was localized only in the narrower equatorial regions in Ect2-depleted cells, and disappeared from the midzone accompanying the progression of the mitotic phase in C3-loaded cells. Stabilization of MTs by taxol was sufficient to maintain the midzone structures in C3-loaded mitotic cells. These results, when combined with a preceding analysis on another, microtubule-associated Rho GEF (C.J. Bakal, D. Finan, J. LaRose, C.D. Wells, G. Gish, S. Kulkarni, P. DeSepulveda, A. Wilde, R. Rottapel, The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis, Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 9529-9534), suggest that mammalian cells have two potential steps that require active Rho for the stabilization of midzone MTs during mitosis and cytokinesis.

  19. F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling

    Science.gov (United States)

    Heemskerk, Niels; Schimmel, Lilian; Oort, Chantal; van Rijssel, Jos; Yin, Taofei; Ma, Bin; van Unen, Jakobus; Pitter, Bettina; Huveneers, Stephan; Goedhart, Joachim; Wu, Yi; Montanez, Eloi; Woodfin, Abigail; van Buul, Jaap D.

    2016-01-01

    During immune surveillance and inflammation, leukocytes exit the vasculature through transient openings in the endothelium without causing plasma leakage. However, the exact mechanisms behind this intriguing phenomenon are still unknown. Here we report that maintenance of endothelial barrier integrity during leukocyte diapedesis requires local endothelial RhoA cycling. Endothelial RhoA depletion in vitro or Rho inhibition in vivo provokes neutrophil-induced vascular leakage that manifests during the physical movement of neutrophils through the endothelial layer. Local RhoA activation initiates the formation of contractile F-actin structures that surround emigrating neutrophils. These structures that surround neutrophil-induced endothelial pores prevent plasma leakage through actomyosin-based pore confinement. Mechanistically, we found that the initiation of RhoA activity involves ICAM-1 and the Rho GEFs Ect2 and LARG. In addition, regulation of actomyosin-based endothelial pore confinement involves ROCK2b, but not ROCK1. Thus, endothelial cells assemble RhoA-controlled contractile F-actin structures around endothelial pores that prevent vascular leakage during leukocyte extravasation. PMID:26814335

  20. RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription

    Science.gov (United States)

    Gerald, Damien; Adini, Irit; Shechter, Sharon; Perruzzi, Carole; Varnau, Joseph; Hopkins, Benjamin; Kazerounian, Shiva; Kurschat, Peter; Blachon, Stephanie; Khedkar, Santosh; Bagchi, Mandrita; Sherris, David; Prendergast, George C.; Klagsbrun, Michael; Stuhlmann, Heidi; Rigby, Alan C.; Nagy, Janice A.; Benjamin, Laura E.

    2013-11-01

    Mechanisms governing the distinct temporal dynamics that characterize post-natal angiogenesis and lymphangiogenesis elicited by cutaneous wounds and inflammation remain unclear. RhoB, a stress-induced small GTPase, modulates cellular responses to growth factors, genotoxic stress and neoplastic transformation. Here we show, using RhoB null mice, that loss of RhoB decreases pathological angiogenesis in the ischaemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge. We link these unique and opposing roles of RhoB in blood versus lymphatic vasculatures to the RhoB-mediated differential regulation of sprouting and proliferation in primary human blood versus lymphatic endothelial cells. We demonstrate that nuclear RhoB-GTP controls expression of distinct gene sets in each endothelial lineage by regulating VEZF1-mediated transcription. Finally, we identify a small-molecule inhibitor of VEZF1-DNA interaction that recapitulates RhoB loss in ischaemic retinopathy. Our findings establish the first intra-endothelial molecular pathway governing the phased response of angiogenesis and lymphangiogenesis following injury.

  1. 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.

  2. Further work on sodium borates as sacrificial materials for a core-catcher

    International Nuclear Information System (INIS)

    Dalle Donne, M.; Dorner, S.; Roth, A.; Werle, H.

    1982-01-01

    Sodium borates are suitable low melting point sacrificial materials for a core-catcher of a fast reactor. Concept, design and initial development work have been described previously. Here we report on the measurements of density, volumetric thermal expansion coefficients and viscosity of borax and sodium metaborate, pure and with various percentages of dissolved UO 2 . The density of these molten salts was measured with the buoyancy method in the temperature range 850 - 1300 0 C, while the viscosity was measured in the temperature range 700 - 1250 0 C with a Haake viscosity balance. Simulation experiments with low melting point materials were performed to investigate the ratio of the downward to sideward melt velocity. The results of these experiments show that this ratio is equal to 0.34 for a solid to liquid density ratio rho = 1.66. For the real borax core-catcher rho = 4 and this would correspond to a velocity ratio of about one

  3. Multi-core Microprocessors

    Indian Academy of Sciences (India)

    core processors. Abstract. Multi-core microprocessor is an interconnected set of independentprocessors called cores integrated on a single siliconchip. These processing cores communicate and cooperatewith one another to execute one or more ...

  4. The RhoGAP activity of myosin IXB is critical for osteoclast podosome patterning, motility, and resorptive capacity.

    Directory of Open Access Journals (Sweden)

    Brooke K McMichael

    Full Text Available Osteoclasts are large, multinucleated cells of the monocyte-macrophage lineage that generate specialized substrate adhesion complexes to facilitate their function as bone-degrading cells. The patterning and function of these actin-based complexes, podosomes and sealing zones, are regulated by the small GTPase Rho. Myosin IXB (Myo9b is a unique actin-based motor protein that contains a RhoGAP domain, which, like other RhoGAPs, is inhibitory to Rho signaling. In this study, Myo9b is shown to be expressed in osteoclasts and act as a critical regulator of podosome patterning and osteoclast function. SiRNA-mediated knockdown of Myo9b results in increased activity of Rho but not Rac in osteoclasts. Knockdown in osteoclasts on glass results in altered podosome patterning and decreased motility, and this effect is reversed by addition of a Rho inhibitor. SiRNA-mediated suppression of Myo9b expression in osteoclasts on bone results in a dramatic loss of resorptive capacity even though sealing zones appear normal. This loss of resorption is also reversible with addition of a Rho inhibitor. Cells with diminished Myo9b levels display mislocalization and suppressed activation of Src, a tyrosine kinase with critical effects on osteoclast actin cytoskeletal rearrangement and function. In addition, siRNA-treated cells display poorly formed microtubule networks and a lack of tubulin acetylation, a marker of microtubule stability. However, short-term addition of TNFα to cells with suppressed Myo9b levels overcomes or circumvents these defects and causes increased sealing zone size and resorptive capacity. These results indicate that the RhoGAP activity of Myo9b plays a key role in regulating the actin-based structures necessary for osteoclast motility and resorption, and confirms that Myo9b can act as a motorized signaling molecule that links Rho signaling to the dynamic actin cytoskeleton.

  5. Magic angle effect plays a major role in both T1rho and T2 relaxation in articular cartilage.

    Science.gov (United States)

    Shao, H; Pauli, C; Li, S; Ma, Y; Tadros, A S; Kavanaugh, A; Chang, E Y; Tang, G; Du, J

    2017-12-01

    To investigate the effect of sample orientation on T1rho and T2 values of articular cartilage in histologically confirmed normal and abnormal regions using a whole-body 3T scanner. Eight human cadaveric patellae were evaluated using a 2D CPMG sequence for T2 measurement as well as a 2D spin-locking prepared spiral sequence and a 3D magnetization-prepared angle-modulated partitioned-k-space spoiled gradient echo snapshots (3D MAPSS) sequence for T1rho measurement. Each sample was imaged at six angles from 0° to 100° relative to the B 0 field. T2 and T1rho values were measured for three regions (medial, apex and lateral) with three layers (10% superficial, 60% middle, 30% deep). Multiple histopathologically confirmed normal and abnormal regions were used to evaluate the angular dependence of T2 and T1rho relaxation in articular cartilage. Our study demonstrated a strong magic angle effect for T1rho and T2 relaxation in articular cartilage, especially in the deeper layers of cartilage. On average, T2 values were increased by 231.8% (72.2% for superficial, 237.6% for middle, and 187.9% for deep layers) while T1rho values were increased by 92% (31.7% for superficial, 69% for middle, and 140% for deep layers) near the magic angle. Both normal and abnormal cartilage showed similar T1rho and T2 magic angle effect. Changes in T1rho and T2 values due to the magic angle effect can be several times more than that caused by degeneration, and this may significantly complicate the clinical application of T1rho and T2 as an early surrogate marker for degeneration. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. A Search for O2 in CO-Depleted Molecular Cloud Cores With Herschel

    Science.gov (United States)

    Wirstroem, Eva S.; Charnley, Steven B.; Cordiner, Martin; Ceccarelli, Cecilia

    2016-01-01

    The general lack of molecular oxygen in molecular clouds is an outstanding problem in astrochemistry. Extensive searches with the Submillimeter Astronomical Satellite, Odin, and Herschel have only produced two detections; upper limits to the O2 abundance in the remaining sources observed are about 1000 times lower than predicted by chemical models. Previous atomic oxygen observations and inferences from observations of other molecules indicated that high abundances of O atoms might be present in dense cores exhibiting large amounts of CO depletion. Theoretical arguments concerning the oxygen gas-grain interaction in cold dense cores suggested that, if O atoms could survive in the gas after most of the rest of the heavy molecular material has frozen out onto dust, then O2 could be formed efficiently in the gas. Using Herschel HIFI, we searched a small sample of four depletion cores-L1544, L694-2, L429, and Oph D-for emission in the low excitation O2 N(sub J)?=?3(sub 3)-1(sub 2) line at 487.249 GHz. Molecular oxygen was not detected and we derive upper limits to its abundance in the range of N(O2)/N (H2) approx. = (0.6-1.6) x10(exp -7). We discuss the absence of O2 in the light of recent laboratory and observational studies.

  7. Increase of RhoB in {gamma}-radiation-induced apoptosis is regulated by c-Jun N-terminal kinase in Jurkat T cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chun-Ho [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Won, Misun; Choi, Chung-Hae; Ahn, Jiwon; Kim, Bo-Kyung [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Song, Kyung-Bin [Department of Food Science and Technology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kang, Chang-Mo, E-mail: kangcm@kcch.re.kr [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Chung, Kyung-Sook, E-mail: kschung@kribb.re.kr [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2010-01-08

    The Ras-related small GTP-binding protein RhoB is known to be a pro-apoptotic protein and immediate-early inducible by genotoxic stresses. In addition, JNK activation is known to function in {gamma}-radiation-induced apoptosis. However, it is unclear how JNK activation and {gamma}-radiation-dependent RhoB induction are related. Here we verified the relationship between JNK activation and RhoB induction. RhoB induction by {gamma}-radiation occurred at the transcriptional level and transcriptional activation of RhoB was concomitant with an increase in RhoB protein. {gamma}-Radiation-induced RhoB expression was markedly attenuated by pretreatment with a JNK-specific inhibitor, SP600125, but not by a p38 MAPK inhibitor, SB203580. Inhibition of JNK caused a decrease in early apoptotic cell death that correlated with RhoB expression. However, PI3K inhibition had no significant effects, indicating that the AKT survival pathway was not involved. The siRNA knockdown of JNK resulted in a decrease in RhoB expression and the siRNA knockdown of RhoB restored cell growth even in the {gamma}-irradiated cells. These results suggest that RhoB regulation involves the JNK pathway and contributes to the early apoptotic response of Jurkat T cells to {gamma}-radiation.

  8. 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

  9. Rho GTPases and Nox dependent ROS production in skin. Is there a connection?

    DEFF Research Database (Denmark)

    Stanley, Alanna; Hynes, Ailish; Brakebusch, Cord Herbert

    2012-01-01

    Rho GTPases are a family of small GTP binding proteins most commonly known for the regulation of many cellular processes, including actin cytoskeleton re-organisation, cell proliferation, signal transduction and regulation of apoptosis. Additionally, a link between Rho GTPases and reactive oxygen...... species (ROS) has been shown. In line with the growing interest in the role of ROS in cell biology, the relevance of this connection is becoming increasingly clearer. ROS production is classically associated with oxidative metabolic pathways (e.g. respiratory chain, arachidonic acid). During...... these metabolic pathways, ROS are produced as by-products and these can be potentially toxic. However, numerous cell types contain dedicated enzymatic complexes, i.e., NADPH oxidase (Nox) complexes, for regulated production of ROS. This regulated production of ROS seems to be important for a number of fundamental...

  10. 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...... the regulation of NADPH oxidase (Nox) activity. This review focuses on relationships between Nox-regulated ROS, Rho GTPases, and cytoskeletal reorganization, in the context of cell migration. Recent Advances: It has become clear that ROS participate in the regulation of certain Rho GTPase family members, thus...

  11. 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.)

  12. 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.)

  13. Efficacy of Rho-Kinase Inhibitor Fasudil in Secondary Raynaud’s Phenomenon

    Science.gov (United States)

    Fava, Andrea; Wung, Peter K; Wigley, Fredrick M; Hummers, Laura K; Daya, Natalie R.; Ghazarian, Sharon R.; Boin, Francesco

    2012-01-01

    Objective The RhoA/Rho-kinase pathway plays a pivotal role in cold induced vasoconstriction, vascular smooth muscle cells function and vascular homeostasis. This study evaluates the efficacy of fasudil, a RhoA/Rho-kinase inhibitor, to reverse cold-induced vasospasm in patients with Raynaud’s phenomenon (RP) secondary to systemic sclerosis (SSc). Methods This is a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of oral fasudil (40 mg or 80 mg) or placebo administered 2 hours before a standardized cold challenge. The fall in skin temperature after the cold challenge and time to recover 50% and 70% of pre-challenge digital skin temperature were used as primary outcomes. Digital blood flow assessed by Laser Doppler, time to minimum skin temperature, and rate of skin cooling were also measured. Results Seventeen patients with SSc and RP completed the study. After cold challenge, skin temperatures and the average time (minutes) to recover 50% (placebo: 7.9, fasudil 40 mg: 7.5, and fasudil 80 mg: 8.2; p=.791) and 70% (placebo: 18.2, fasudil 40 mg: 15.0, and fasudil 80 mg: 17.1; p=.654) of pre-challenge skin temperature were not significantly different across the three groups. The digital blood flow measurements were higher in fasudil treated groups than placebo but differences were not significant (p=.693). Conclusions Fasudil administered at single oral dose of 40 mg or 80 mg was not associated with significant benefit in term of skin temperature recovery time and digital blood flow after cold challenge. PMID:22275160

  14. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Tracy Vargo-Gogola

    2012-04-01

    Full Text Available 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.

  15. Rho-associated kinase inhibitor eye drop (Ripasudil) transiently alters the morphology of corneal endothelial cells

    OpenAIRE

    Okumura, Naoki; Okazaki, Yugo; Inoue, Ryota; Nakano, Shinichiro; Fullwood, Nigel J.; Kinoshita, Shigeru; Koizumi, Noriko

    2015-01-01

    PURPOSE: Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS: Morphological changes in the corneal endothelium were evaluated in human subjects by specular and slit...

  16. MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Céline Sabatel

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated. METHODOLOGY/PRINCIPAL FINDINGS: We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization. CONCLUSIONS/SIGNIFICANCE: Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB.

  17. 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

  18. Increased adenovirus Type 5 mediated transgene expression due to RhoB down-regulation.

    Directory of Open Access Journals (Sweden)

    Dragomira Majhen

    Full Text Available Adenovirus type 5 (Ad5 is a non-enveloped DNA virus frequently used as a gene transfer vector. Efficient Ad5 cell entry depends on the availability of its primary receptor, coxsackie and adenovirus receptor, which is responsible for attachment, and integrins, secondary receptors responsible for adenovirus internalization via clathrin-mediated endocytosis. However, efficacious adenovirus-mediated transgene expression also depends on successful trafficking of Ad5 particles to the nucleus of the target cell. It has been shown that changes occurring in tumor cells during development of resistance to anticancer drugs can be beneficial for adenovirus mediated transgene expression. In this study, using an in vitro model consisting of a parental cell line, human laryngeal carcinoma HEp2 cells, and a cisplatin-resistant clone CK2, we investigated the cause of increased Ad5-mediated transgene expression in CK2 as compared to HEp2 cells. We show that the primary cause of increased Ad5-mediated transgene expression in CK2 cells is not modulation of receptors on the cell surface or change in Ad5wt attachment and/or internalization, but is rather the consequence of decreased RhoB expression. We propose that RhoB plays an important role in Ad5 post-internalization events and more particularly in Ad5 intracellular trafficking. To the best of our knowledge, this is the first study showing changed Ad5 trafficking pattern between cells expressing different amount of RhoB, indicating the role of RhoB in Ad5 intracellular trafficking.

  19. 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

  20. Study of the doubly radiative decay J /. psi. r arrow. gamma. gamma. rho. sup 0

    Energy Technology Data Exchange (ETDEWEB)

    Coffman, D.; DeJongh, F.; Dubois, G.; Eigen, G.; Hauser, J.; Hitlin, D.G.; Matthews, C.G.; Mincer, A.; Richman, J.D.; Wisniewski, W.J.; Zhu, Y. (California Institute of Technology, Pasadena, California 91125 (USA)); Burchell, M.; Dorfan, D.E.; Drinkard, J.; Gatto, C.; Hamilton, R.P.; Heusch, C.A.; Koepke, L.; Lockman, W.S.; Partridge, R.; Sadrozinski, H.F.W.; Scarlatella, M.; Schalk, T.L.; Seiden, A.; Weinstein, A.J.; Weseler, S.; Xu, R. (University of California at Santa Cruz, Santa Cruz, California 95064 (USA)); Becker, J.J.; Blaylock, G.T.; Eisenstein, B.I.; Freese, T.; Gladding, G.; Izen, J.M.; Plaetzer, S.A.; Simopoulos, C.; Spadafora, A.L.; Stockdale, I.E.; Tripsas, B. (University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (USA)); Mallik, U.; Roco, M.; Wang, M.Z. (University of Iowa, Iowa City, Iowa 52242 (USA)); Adler, J.; Bolton, T.; Brient, J.C.; Bunnell, K.O.; Cassell, R.E.; Coward, D.H.; Einsweiler, K.F.; Grab, C.; Kim, P.C.; Labs, J.; Odian, A.; Pitman, D.; The Mark III Collaboration

    1990-03-01

    We present a study of the decay sequence {ital J}/{psi}{r arrow}{gamma}{ital X}, {ital X}{r arrow}{gamma}{rho}{sup 0}, {rho}{sup 0}{r arrow}{pi}{sup +}{pi}{sup {minus}}, based on 5.8{times}10{sup 6} produced {ital J}/{psi} collected by the Mark III detector at the SLAC storage ring SPEAR. In the {gamma}{rho}{sup 0} mass spectrum, we find two peaks with masses and widths consistent with the axial-vector mesons {ital f}{sub 1}(1285) and {ital f}{sub 1}(1420) that have recently been observed in two-photon collisions. Fits to the angular distributions confirm that the first peak is an axial-vector state, but are unable to distinguish between the {ital f}{sub 1}(1420) or the pseudoscalar {eta}(1430) for the high-mass peak. Product branching fractions for both objects are presented.

  1. 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

  2. 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.)

  3. 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...

  4. 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)

  5. Actin, RhoA, and Rab11 participation during encystment in Entamoeba invadens.

    Science.gov (United States)

    Herrera-Martínez, M; Hernández-Ramírez, V I; Lagunes-Guillén, A E; Chávez-Munguía, B; Talamás-Rohana, P

    2013-01-01

    In the genus Entamoeba, actin reorganization is necessary for cyst differentiation; however, its role is still unknown. The aim of this work was to investigate the role of actin and encystation-related proteins during Entamoeba invadens encystation. Studied proteins were actin, RhoA, a small GTPase involved through its effectors in the rearrangement of the actin cytoskeleton; Rab11, a protein involved in the transport of encystation vesicles; and enolase, as an encystment vesicles marker. Results showed a high level of polymerized actin accompanied by increased levels of RhoA-GTP during cell rounding and loss of vacuoles. Cytochalasin D, an actin polymerization inhibitor, and Y27632, an inhibitor of RhoA activity, reduced encystment in 80%. These inhibitors also blocked cell rounding, disposal of vacuoles, and the proper formation of the cysts wall. At later times, F-actin and Rab11 colocalized with enolase, suggesting that Rab11 could participate in the transport of the cyst wall components through the F-actin cytoskeleton. These results suggest that actin cytoskeleton rearrangement is playing a decisive role in determining cell morphology changes and helping with the transport of cell wall components to the cell surface during encystment of E. invadens.

  6. RhoB promotes cancer initiation by protecting keratinocytes from UVB-induced apoptosis but limits tumor aggressiveness.

    Science.gov (United States)

    Meyer, Nicolas; Peyret-Lacombe, Alexis; Canguilhem, Bruno; Médale-Giamarchi, Claire; Mamouni, Kenza; Cristini, Agnese; Monferran, Sylvie; Lamant, Laurence; Filleron, Thomas; Pradines, Anne; Sordet, Olivier; Favre, Gilles

    2014-01-01

    The role of UVB-induced apoptosis in the formation of squamous cell carcinoma (SCC) is recognized. We previously identified the small RhoB (Ras homolog gene family, member B) GTPase, an early response gene to cellular stress, as a critical protein controlling apoptosis of human keratinocytes after UVB exposure. Here we generated SKH1 (hairless immunocompetent mouse) mice invalidated for RhoB to evaluate its role in UVB-induced skin carcinogenesis in vivo. We show that rhob-/- mice have a lower risk of developing UVB-induced keratotic tumors and actinic keratosis that is associated with a higher sensitivity of UVB-exposed keratinocytes to apoptosis. We extend this observation to primary cultures of normal human keratinocytes in which RhoB was downregulated with small interfering RNA (siRNA) and further show that the hypersensitivity to apoptosis depends on B-cell lymphoma 2 (Bcl-2) downregulation. In rhob-/- mice, the UVB-induced tumors were preferentially undifferentiated and highly proliferative. Finally, we show in humans an almost constant loss of RhoB expression in undifferentiated SCCs. These undifferentiated and RhoB-deficient tumors have elevated phosphorylated histone H2AX (γH2AX) and 53BP1, two markers of DNA double-strand breaks. Together, our results indicate that UVB-induced RhoB expression participates in in vivo SCC initiation by increasing keratinocyte survival. Conversely, RhoB may limit tumor aggressiveness as loss of RhoB expression in tumor cells is associated with tumor progression.

  7. 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.

  8. 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.)

  9. 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}.

  10. RhoE is regulated by cyclic AMP and promotes fusion of human BeWo choriocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Gavin P Collett

    Full Text Available Fusion of placental villous cytotrophoblasts with the overlying syncytiotrophoblast is essential for the maintenance of successful pregnancy, and disturbances in this process have been implicated in pathological conditions such as pre-eclampsia and intra-uterine growth retardation. In this study we examined the role of the Rho GTPase family member RhoE in trophoblast differentiation and fusion using the BeWo choriocarcinoma cell line, a model of villous cytotrophoblast fusion. Treatment of BeWo cells with the cell permeable cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP resulted in a strong upregulation of RhoE at 24 h, coinciding with the onset of fusion. Using the protein kinase A (PKA-specific cAMP analogue N(6-phenyl-cAMP, and a specific inhibitor of PKA (14-22 amide, PKI, we found that upregulation of RhoE by cAMP was mediated through activation of PKA signalling. Silencing of RhoE expression by RNA interference resulted in a significant decrease in dbcAMP-induced fusion. However, expression of differentiation markers human chorionic gonadotrophin and placental alkaline phosphatase was unaffected by RhoE silencing. Finally, we found that RhoE upregulation by dbcAMP was significantly reduced under hypoxic conditions in which cell fusion is impaired. These results show that induction of RhoE by cAMP is mediated through PKA and promotes BeWo cell fusion but has no effect on functional differentiation, supporting evidence that these two processes may be controlled by separate or diverging pathways.

  11. An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells.

    Science.gov (United States)

    Schrade, Katharina; Tröger, Jessica; Eldahshan, Adeeb; Zühlke, Kerstin; Abdul Azeez, Kamal R; Elkins, Jonathan M; Neuenschwander, Martin; Oder, Andreas; Elkewedi, Mohamed; Jaksch, Sarah; Andrae, Karsten; Li, Jinliang; Fernandes, Joao; Müller, Paul Markus; Grunwald, Stephan; Marino, Stephen F; Vukićević, Tanja; Eichhorst, Jenny; Wiesner, Burkhard; Weber, Marcus; Kapiloff, Michael; Rocks, Oliver; Daumke, Oliver; Wieland, Thomas; Knapp, Stefan; von Kries, Jens Peter; Klussmann, Enno

    2018-01-01

    Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.

  12. 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.

  13. RhoA increases ASIC1a plasma membrane localization and calcium influx in pulmonary arterial smooth muscle cells following chronic hypoxia.

    Science.gov (United States)

    Herbert, Lindsay M; Resta, Thomas C; Jernigan, Nikki L

    2018-02-01

    Increases in pulmonary arterial smooth muscle cell (PASMC) intracellular Ca 2+ levels and enhanced RhoA/Rho kinase-dependent Ca 2+ sensitization are key determinants of PASMC contraction, migration, and proliferation accompanying the development of hypoxic pulmonary hypertension. We previously showed that acid-sensing ion channel 1a (ASIC1a)-mediated Ca 2+ entry in PASMC is an important constituent of the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with hypoxic pulmonary hypertension. However, the enhanced ASIC1a-mediated store-operated Ca 2+ entry in PASMC from pulmonary hypertensive animals is not dependent on an increase in ASIC1a protein expression, suggesting that chronic hypoxia (CH) stimulates ASIC1a function through other regulatory mechanism(s). RhoA is involved in ion channel trafficking, and levels of activated RhoA are increased following CH. Therefore, we hypothesize that activation of RhoA following CH increases ASIC1a-mediated Ca 2+ entry by promoting ASIC1a plasma membrane localization. Consistent with our hypothesis, we found greater plasma membrane localization of ASIC1a following CH. Inhibition of RhoA decreased ASIC1a plasma membrane expression and largely diminished ASIC1a-mediated Ca 2+ influx, whereas activation of RhoA had the opposite effect. A proximity ligation assay revealed that ASIC1a and RhoA colocalize in PASMC and that the activation state of RhoA modulates this interaction. Together, our findings show a novel interaction between RhoA and ASIC1a, such that activation of RhoA in PASMC, both pharmacologically and via CH, promotes ASIC1a plasma membrane localization and Ca 2+ entry. In addition to enhanced RhoA-mediated Ca 2+ sensitization following CH, RhoA can also activate a Ca 2+ signal by facilitating ASIC1a plasma membrane localization and Ca 2+ influx in pulmonary hypertension.

  14. Role of Rho proteins in carbachol-induced contractions in intact and permeabilized guinea-pig intestinal smooth muscle.

    Science.gov (United States)

    Otto, B; Steusloff, A; Just, I; Aktories, K; Pfitzer, G

    1996-01-01

    1. The aim of this study was to determine whether the low molecular mass GTPase RhoA or related proteins are involved in carbachol- and high-K(+)-induced contractions in intact intestinal smooth muscle as well as the carbachol-induced increase in Ca2+ sensitivity of the myofilaments in permeabilized preparations. 2. The carbachol-induced increase in the Ca2+ sensitivity of force production in beta-escin-permeabilized intestinal smooth muscle was enhanced in preparations that were loaded with the constitutively active mutant of RhoA, Val14RhoA, and was inhibited by exoenzyme C3 from Clostridium botulinum, which ADP-ribosylates and inactivates small GTPases of the Rho family. The effect of C3 on Ca2+ sensitivity in the absence of the agonist was negligible, while the maximal Ca(2+)-activated force was inhibited by about 20%. 3. Inhibition of carbachol-induced force was associated with an increase in ADP-ribosylation of a protein band with a molecular mass of approximately 22 kDa, corresponding to Rho, and was partially reversed in the presence of Ile41RhoA, which is not a substrate for C3. Val14RhoA did not restore carbachol-induced Ca2+ sensitization in C3-treated smooth muscle. 4. In intact intestinal smooth muscle, toxin B from Clostridium difficile, which monoglucosylates members of the Rho family, inhibited high-K(+)-induced contractions and the initial phasic response to carbachol by about 30%. The delayed contractile response to carbachol was completely inhibited. 5. In smooth muscle preparations that were permeabilized with beta-escin after treatment with toxin B, carbachol-and GTP gamma S-induced Ca2+ sensitization was significantly inhibited. 6. These findings are consistent with a role for Rho or Rho-like proteins in agonist-induced increase in Ca2+ sensitivity of force production in intact and permeabilized intestinal smooth muscle. Images Figure 2 PMID:8910218

  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. Pennogenin tetraglycoside induces rat myometrial contraction and MLC20 phosphorylation via PLC-IP(3 and RhoA/Rho kinase signaling pathways.

    Directory of Open Access Journals (Sweden)

    Limei Wang

    Full Text Available BACKGROUND: Total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs have been widely used in China for the treatment of abnormal uterine bleeding. We previously studied the main active constituents of TSSPs and their structure-activity relationships with respect to rat myometrial contractions. Tg (pennogenin tetraglycoside was identified as one of the active ingredients in TSSPs able to induce rat myometrial contractions. However, the mechanisms underlying the pharmacological actions on uterine activity have not been described clearly. METHODS: Here Tg was screened for effects on contractile activity in isolated uterine strips from estrogen-primed rats and on MLC20 phosphorylation and related signaling pathways in cultured rat myometrial cells as determined by Western blot. Intracellular calcium ([Ca(2+](i was monitored under a confocal microscope using Fluo-4 AM-loaded myometrial cells. RESULTS: Tg dose-dependently stimulated rat myometrial contractions as well as MLC20 phosphorylation in vitro, which could be completely suppressed by an inhibitor of myosin light chain kinase (MLCK. Use of Ca(2+ channel blockers and kinase inhibitors demonstrated that Tg-induced myometrial contractions are mediated by activation of the phospholipase C (PLC-inositol triphosphate (IP3 signaling pathway, resulting in increased MLC20 phosphorylation. Furthermore, Y27632, a specific inhibitor of Rho kinase (ROK, notably suppressed Tg-stimulated myometrial contractions and decreased MLC20 phosphorylation. CONCLUSIONS: These data provide evidence that rat myometrial contractility induced by Tg results from enhanced MLC20 phosphorylation, while both PLC-IP3 and RhoA/ROK signaling pathways mediate the process. These mechanisms may be responsible for the therapeutic effects of TSSPs on abnormal uterine bleeding.

  17. Animal MRI Core

    Data.gov (United States)

    Federal Laboratory Consortium — The Animal Magnetic Resonance Imaging (MRI) Core develops and optimizes MRI methods for cardiovascular imaging of mice and rats. The Core provides imaging expertise,...

  18. RhoA Signaling and Synaptic Damage Occur Within Hours in a Live Pig Model of CNS Injury, Retinal Detachment

    Science.gov (United States)

    Wang, Jianfeng; Zarbin, Marco; Sugino, Ilene; Whitehead, Ian; Townes-Anderson, Ellen

    2016-01-01

    Purpose The RhoA pathway is activated after retinal injury. However, the time of onset and consequences of activation are unknown in vivo. Based on in vitro studies we focused on a period 2 hours after retinal detachment, in pig, an animal whose retina is holangiotic and contains cones. Methods Under anesthesia, retinal detachments were created by subretinal injection of a balanced salt solution. Two hours later, animals were sacrificed and enucleated for GTPase activity assays and quantitative Western blot and confocal microscopy analyses. Results RhoA activity with detachment was increased 1.5-fold compared to that in normal eyes or in eyes that had undergone vitrectomy only. Increased phosphorylation of myosin light chain, a RhoA effector, also occurred. By 2 hours, rod cells had retracted their terminals toward their cell bodies, disrupting the photoreceptor-to-bipolar synapse and producing significant numbers of spherules with SV2 immunolabel in the outer nuclear layer of the retina. In eyes with detachment, distant retina that remained attached also showed significant increases in RhoA activity and synaptic disjunction. Increases in RAC1 activity and glial fibrillary acidic protein (GFAP) were not specific for detachment, and sprouting of bipolar dendrites, reported for longer detachments, was not seen. The RhoA kinase inhibitor Y27632 significantly reduced axonal retraction by rod cells. Conclusions Activation of the RhoA pathway occurs quickly after injury and promotes synaptic damage that can be controlled by RhoA kinase inhibition. We suggest that retinal detachment joins the list of central nervous system injuries, such as stroke and spinal cord injury, that should be considered for rapid therapeutic intervention. PMID:27472075

  19. 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

  20. 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

  1. The nuclear guanine nucleotide exchange factors Ect2 and Net1 regulate RhoB-mediated cell death after DNA damage.

    Directory of Open Access Journals (Sweden)

    Melissa C Srougi

    2011-02-01

    Full Text Available Commonly used antitumor treatments, including radiation and chemotherapy, function by damaging the DNA of rapidly proliferating cells. However, resistance to these agents is a predominant clinical problem. A member of the Rho family of small GTPases, RhoB has been shown to be integral in mediating cell death after ionizing radiation (IR or other DNA damaging agents in Ras-transformed cell lines. In addition, RhoB protein expression increases after genotoxic stress, and loss of RhoB expression causes radio- and chemotherapeutic resistance. However, the signaling pathways that govern RhoB-induced cell death after DNA damage remain enigmatic. Here, we show that RhoB activity increases in human breast and cervical cancer cell lines after treatment with DNA damaging agents. Furthermore, RhoB activity is necessary for DNA damage-induced cell death, as the stable loss of RhoB protein expression using shRNA partially protects cells and prevents the phosphorylation of c-Jun N-terminal kinases (JNKs and the induction of the pro-apoptotic protein Bim after IR. The increase in RhoB activity after genotoxic stress is associated with increased activity of the nuclear guanine nucleotide exchange factors (GEFs, Ect2 and Net1, but not the cytoplasmic GEFs p115 RhoGEF or Vav2. Importantly, loss of Ect2 and Net1 via siRNA-mediated protein knock-down inhibited IR-induced increases in RhoB activity, reduced apoptotic signaling events, and protected cells from IR-induced cell death. Collectively, these data suggest a mechanism involving the nuclear GEFs Ect2 and Net1 for activating RhoB after genotoxic stress, thereby facilitating cell death after treatment with DNA damaging agents.

  2. 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.

  3. Industrial PM2.5cause 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.

  4. Echovirus 30 induced neuronal cell death through TRIO-RhoA signaling activation.

    Directory of Open Access Journals (Sweden)

    June-Woo Lee

    Full Text Available BACKGROUND: Echovirus 30 (Echo30 is one of the most frequently identified human enteroviruses (EVs causing aseptic meningitis and encephalitis. However the mechanism underlying the pathogenesis of Echo30 infection with significant clinical outcomes is not completely understood. The aim of this investigation is to illustrate molecular pathologic alteration in neuronal cells induced by Echo30 infection using clinical isolate from young patient with neurologic involvement. METHODOLOGY/PRINCIPAL FINDINGS: To characterize the neuronal cellular response to Echo30 infection, we performed a proteomic analysis based on two-dimensional gel electrophoresis (2-DE and MALDI-TOF/TOF Mass Spectrophotometric (MS analysis. We identified significant alteration of several protein expression levels in Echo30-infected SK-N-SH cells. Among these proteins, we focused on an outstanding up-regulation of Triple functional domain (TRIO in Echo30-infected SK-N-SH cells. Generally, TRIO acts as a key component in the regulation of axon guidance and cell migration. In this study, we determined that TRIO plays a role in the novel pathways in Echo30 induced neuronal cell death. CONCLUSIONS/SIGNIFICANCE: Our finding shows that TRIO plays a critical role in neuronal cell death by Echo30 infection. Echo30 infection activates TRIO-guanine nucleotide exchange factor (GEF domains (GEFD2 and RhoA signaling in turn. These results suggest that Echo30 infection induced neuronal cell death by activation of the TRIO-RhoA signaling. We expect the regulation of TRIO-RhoA signaling may represent a new therapeutic approach in treating aseptic meningitis and encephalitis induced by Echo30.

  5. Inclusive photoproduction of {rho}{sup 0}, K{sup *0} and {phi} mesons at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Aaron, F.D. [National Inst. for Physics and Nuclear Engineering (NIPNE), Bucharest (Romania)]|[Bucharest Univ. (Romania). Faculty of Physics; Alexa, C. [National Inst. for Physics and Nuclear Engineering (NIPNE), Bucharest (Romania); Andreev, V. [Lebedev Physical Inst., Moscow (RU)] (and others)

    2008-12-15

    Inclusive non-diffractive photoproduction of {rho}(770){sup 0}, K{sup *}(892){sup 0} and {phi}(1020) mesons is investigated with the H1 detector in ep collisions at HERA. The corresponding average {gamma}p centre-of-mass energy is 210 GeV. The mesons are measured in the transverse momentum range 0.5

  6. 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

  7. 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.

  8. Inclusive Photoproduction of rho^0, K^{*0} and phi Mesons at HERA

    CERN Document Server

    Aaron, F.D.; Andreev, V.; Antunovic, B.; Aplin, S.; Asmone, A.; Astvatsatourov, A.; Backovic, S.; Baghdasaryan, A.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Behnke, O.; Belousov, A.; Berger, N.; 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 Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Falkiewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D.-J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, Samvel; Glazov, A.; Glushkov, I.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Hansson, M.; 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.; Jemanov, V.; Jonsson, L.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kluge, T.; Knutsson, A.; Kogler, R.; Korbel, V.; 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.; Meier, K.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Mudrinic, M.; Muller, K.; Murin, P.; Naroska, B.; 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.; 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.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Smiljanic, Ivan; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, Arnd E.; 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.

    2009-01-01

    Inclusive non-diffractive photoproduction of rho(770)^0, K^*(892)^0 and phi(1020) mesons is investigated with the H1 detector in ep collisions at HERA. The corresponding average \\gamma p centre-of-mass energy is 210 GeV. The mesons are measured in the transverse momentum range 0.5

  9. RhoA/ROCK Signaling Pathway Mediates Shuanghuanglian Injection-Induced Pseudo-allergic Reactions

    Directory of Open Access Journals (Sweden)

    Jiayin Han

    2018-02-01

    Full Text Available 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

  10. Comparison of exchange mechanisms in pi N to rho N and pion photo- and electroproduction

    CERN Document Server

    Irving, A C

    1975-01-01

    Rho-, photo- and electroproduction are compared and contrasted from a t-channel exchange point of view. A common exchange mechanism is evident. Systematic differences associated with the variable mass of the vector particle are found-in particular, the mass dependence of the non-pole-like contributions is reminiscent of that seen in higher mass resonance production. Naive vector meson dominance arguments which do not allow for these mass-dependent effects are shown to disagree both qualitatively and quantitatively with the data. The implications of this, and similar studies, are emphasised for an understanding of absorption effects in two-body scattering. (31 refs).

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.)

  18. 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)

  19. Astaxanthin induces migration in human skin keratinocytes via Rac1 activation and RhoA inhibition.

    Science.gov (United States)

    Ritto, Dakanda; Tanasawet, Supita; Singkhorn, Sawana; Klaypradit, Wanwimol; Hutamekalin, Pilaiwanwadee; Tipmanee, Varomyalin; Sukketsiri, Wanida

    2017-08-01

    Re-epithelialization has an important role in skin wound healing. Astaxanthin (ASX), a carotenoid found in crustaceans including shrimp, crab, and salmon, has been widely used for skin protection. Therefore, we investigated the effects of ASX on proliferation and migration of human skin keratinocyte cells and explored the mechanism associated with that migration. HaCaT keratinocyte cells were exposed to 0.25-1 µg/mL of ASX. Proliferation of keratinocytes was analyzed by using MTT assays and flow cytometry. Keratinocyte migration was determined by using a scratch wound-healing assay. A mechanism for regulation of migration was explored via immunocytochemistry and western blot analysis. Our results suggest that ASX produces no significant toxicity in human keratinocyte cells. Cell-cycle analysis on ASX-treated keratinocytes demonstrated a significant increase in keratinocyte cell proliferation at the S phase. In addition, ASX increased keratinocyte motility across the wound space in a time-dependent manner. The mechanism by which ASX increased keratinocyte migration was associated with induction of filopodia and formation of lamellipodia, as well as with increased Cdc42 and Rac1 activation and decreased RhoA activation. ASX stimulates the migration of keratinocytes through Cdc42, Rac1 activation and RhoA inhibition. ASX has a positive role in the re-epithelialization of wounds. Our results may encourage further in vivo and clinical study into the development of ASX as a potential agent for wound repair.

  20. Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis.

    Science.gov (United States)

    Kümper, Sandra; Mardakheh, Faraz K; McCarthy, Afshan; Yeo, Maggie; Stamp, Gordon W; Paul, Angela; Worboys, Jonathan; Sadok, Amine; Jørgensen, Claus; Guichard, Sabrina; Marshall, Christopher J

    2016-01-14

    Rho-associated kinases 1 and 2 (ROCK1/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here, we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and CDK1. Accordingly, while the loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility.

  1. The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier.

    Science.gov (United States)

    Sugano, Yuya; Lindenmeyer, Maja T; Auberger, Ines; Ziegler, Urs; Segerer, Stephan; Cohen, Clemens D; Neuhauss, Stephan C F; Loffing, Johannes

    2015-11-01

    Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros.

  2. Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

    Directory of Open Access Journals (Sweden)

    Zuojun Xu

    2012-07-01

    Full Text Available The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK, may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-β1 (TGF-β1, connective tissue growth factor (CTGF, alpha-smooth muscle actin (α-SMA, and plasminogen activator inhibitor-1 (PAI-1 mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.

  3. Regulation of RhoA by STAT3 coordinates glial scar formation

    Science.gov (United States)

    Kumamaru, Hiromi; Kawase, Satoshi; Baudoux, Matthieu; Ishibashi, Toshiki; Kawabata, Soya; Nishiyama, Yuichiro; Sugai, Keiko; Yasutake, Kaori; Okada, Seiji; Nakamura, Masaya

    2017-01-01

    Understanding how the transcription factor signal transducer and activator of transcription–3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes. Reduction of phosphatase and tensin homologue (PTEN) levels in STAT3-CKO rescues reactive astrocytes dynamics in vitro. By specific targeting of lesion-proximal, reactive astrocytes in Nestin-Cre mice, we show that reduction of PTEN rescues glial scar formation in Nestin-Stat3+/− mice. These findings reveal novel intracellular signaling mechanisms underlying the contribution of reactive astrocyte dynamics to glial scar formation. PMID:28642362

  4. Yeast Translation Elongation Factor-1A Binds Vacuole-localized Rho1p to Facilitate Membrane Integrity through F-actin Remodeling*

    Science.gov (United States)

    Bodman, James A. R.; Yang, Yang; Logan, Michael R.; Eitzen, Gary

    2015-01-01

    Rho GTPases are molecular switches that modulate a variety of cellular processes, most notably those involving actin dynamics. We have previously shown that yeast vacuolar membrane fusion requires re-organization of actin filaments mediated by two Rho GTPases, Rho1p and Cdc42p. Cdc42p initiates actin polymerization to facilitate membrane tethering; Rho1p has a role in the late stages of vacuolar fusion, but its mode of action is unknown. Here, we identified eEF1A as a vacuolar Rho1p-interacting protein. eEF1A (encoded by the TEF1 and TEF2 genes in yeast) is an aminoacyl-tRNA transferase needed during protein translation. eEF1A also has a second function that is independent of translation; it binds and organizes actin filaments into ordered cable structures. Here, we report that eEF1A interacts with Rho1p via a C-terminal subdomain. This interaction occurs predominantly when both proteins are in the GDP-bound state. Therefore, eEF1A is an atypical downstream effector of Rho1p. eEF1A does not promote vacuolar fusion; however, overexpression of the Rho1p-interacting subdomain affects vacuolar morphology. Vacuoles were destabilized and prone to leakage when treated with the eEF1A inhibitor narciclasine. We propose a model whereby eEF1A binds to Rho1p-GDP on the vacuolar membrane; it is released upon Rho1p activation and then bundles actin filaments to stabilize fused vacuoles. Therefore, the Rho1p-eEF1A complex acts to spatially localize a pool of eEF1A to vacuoles where it can readily organize F-actin. PMID:25561732

  5. k -core covers and the core

    NARCIS (Netherlands)

    Sanchez-Rodriguez, E.; Borm, P.; Estevez Fernandez, M.A.; Fiestras-Janeiro, M.G.; Mosquera, M.A.

    2015-01-01

    This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

  6. k-core covers and the core

    NARCIS (Netherlands)

    Sanchez-Rodriguez, E.; Borm, Peter; Estevez-Fernandez, A.; Fiestras-Janeiro, G.; Mosquera, M.A.

    This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion.

    Directory of Open Access Journals (Sweden)

    Joseph H R Hetmanski

    2016-05-01

    Full Text Available Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN containing extracellular matrix (ECM, by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3 pathway and generate filopodial actin-spike protrusions which drive invasion. To further understand the signalling network that drives RCP-driven invasive migration, we generated a Boolean logical model based on existing network pathways/models, where each node can be interrogated by computational simulation. The model predicted an unanticipated feedback loop, whereby Raf/MEK/ERK signalling maintains suppression of Rac1 by inhibiting the Rac-activating Sos1-Eps8-Abi1 complex, allowing RhoA activity to predominate in invasive protrusions. MEK inhibition was sufficient to promote lamellipodia formation and oppose filopodial actin-spike formation, and led to activation of Rac and inactivation of RhoA at the leading edge of cells moving in 3D matrix. Furthermore, MEK inhibition abrogated RCP/α5β1/EGFR1-driven invasive migration. However, upon knockdown of Eps8 (to suppress the Sos1-Abi1-Eps8 complex, MEK inhibition had no effect on RhoGTPase activity and did not oppose invasive migration, suggesting that MEK-ERK signalling suppresses the Rac-activating Sos1-Abi1-Eps8 complex to maintain RhoA activity and promote filopodial actin-spike formation and invasive migration. Our study highlights the predictive potential of mathematical modelling approaches, and demonstrates that a simple intervention (MEK-inhibition could be of therapeutic benefit in preventing invasive migration and metastasis.

  12. Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats via pleiotropic inhibition of RhoA signaling.

    Science.gov (United States)

    Wong, Mathew J; Kantores, Crystal; Ivanovska, Julijana; Jain, Amish; Jankov, Robert P

    2016-11-01

    Chronic neonatal pulmonary hypertension (PHT) frequently results in early death. Systemically administered Rho-kinase (ROCK) inhibitors prevent and reverse chronic PHT in neonatal rats, but at the cost of severe adverse effects, including systemic hypotension and growth restriction. Simvastatin has pleiotropic inhibitory effects on isoprenoid intermediates that may limit activity of RhoA, which signals upstream of ROCK. We therefore hypothesized that statin treatment would safely limit pulmonary vascular RhoA activity and prevent and reverse experimental chronic neonatal PHT via downstream inhibitory effects on pathological ROCK activity. Sprague-Dawley rats in normoxia (room air) or moderate normobaric hypoxia (13% O 2 ) received simvastatin (2 mg·kg -1 ·day -1 ip) or vehicle from postnatal days 1-14 (prevention protocol) or from days 14-21 (rescue protocol). Chronic hypoxia increased RhoA and ROCK activity in lung tissue. Simvastatin reduced lung content of the isoprenoid intermediate farnesyl pyrophosphate and decreased RhoA/ROCK signaling in the hypoxia-exposed lung. Preventive or rescue treatment of chronic hypoxia-exposed animals with simvastatin decreased pulmonary vascular resistance, right ventricular hypertrophy, and pulmonary arterial remodeling. Preventive simvastatin treatment improved weight gain, did not lower systemic blood pressure, and did not cause apparent toxic effects on skeletal muscle, liver or brain. Rescue therapy with simvastatin improved exercise capacity. We conclude that simvastatin limits RhoA/ROCK activity in the chronic hypoxia-exposed lung, thus preventing or ameliorating hemodynamic and structural markers of chronic PHT and improving long-term outcome, without causing adverse effects. Copyright © 2016 the American Physiological Society.

  13. 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

  14. Funktionelle Analyse von bakteriellen W-xxx-E Rho GTPasen GEF Mimetika mittels Typ 3 Sekretionssystems von Yersinia enterocolitica

    OpenAIRE

    Wölke, Stefan

    2011-01-01

    Die zellulären Rho GTPasen kontrollieren und regulieren zentrale elementare Zellvorgänge wie Phagozytose, Migration und epitheliale Integrität. Aufgrund ihrer zentralen Stellung, interagiert eine Vielzahl von bakteriellen Cytotoxinen und Modulinen mit den Rho GTPasen und wirken so als Pathogenitätsfaktoren. Die zur W-xxx-E Familie gehörenden Effektoren IpgB1 und IpgB2 von Shigella und Map von E. coli (Pathotypen EHEC und EPEC) werden über ein Typ 3 Sekretionssystem (T3SS) in Wirtszellen injiz...

  15. 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.

  16. 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.

  17. 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.

  18. Reactor core fuel management

    International Nuclear Information System (INIS)

    Silvennoinen, P.

    1976-01-01

    The subject is covered in chapters, entitled: concepts of reactor physics; neutron diffusion; core heat transfer; reactivity; reactor operation; variables of core management; computer code modules; alternative reactor concepts; methods of optimization; general system aspects. (U.K.)

  19. Nuclear reactor core catcher

    International Nuclear Information System (INIS)

    1977-01-01

    A nuclear reactor core catcher is described for containing debris resulting from an accident causing core meltdown and which incorporates a method of cooling the debris by the circulation of a liquid coolant. (U.K.)

  20. 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.

  1. Sphingosylphosphorylcholine induces α-smooth muscle actin expression in human lung fibroblasts and fibroblast-mediated gel contraction via S1P2 receptor and Rho/Rho-kinase pathway.

    Science.gov (United States)

    Wang, X Q; Mao, L J; Fang, Q H; Kobayashi, T; Kim, H J; Sugiura, H; Kawasaki, S; Togo, S; Kamio, K; Liu, X; Rennard, S I

    2014-01-01

    Chronic airway diseases like COPD and asthma are usually accompanied with airway fibrosis. Myofibroblasts, which are characterized by expression of smooth muscle actin (α-SMA), play an important role in a variety of developmental and pathological processes, including fibrosis and wound healing. Sphingosylphosphorylcholine (SPC), a sphingolipid metabolite, has been implicated in many physiological and pathological conditions. The current study tested the hypothesis that SPC may modulate tissue remodeling by affecting the expression of α-SMA in human fetal lung fibroblast (HFL-1) and fibroblast mediated gel contraction. The results show that SPC stimulates α-SMA expression in HFL-1 and augments HFL-1 mediated collagen gel contraction in a time- and concentration-dependent manner. The α-SMA protein expression and fibroblast gel contraction induced by SPC was not blocked by TGF-β1 neutralizing antibody. However, it was significantly blocked by S1P2 receptor antagonist JTE-013, the Rho-specific inhibitor C3 exoenzyme, and a Rho-kinase inhibitor Y-27632. These findings suggest that SPC stimulates α-SMA protein expression and HFL-1 mediated collagen gel contraction via S1P2 receptor and Rho/Rho kinase pathway, and by which mechanism, SPC may be involved in lung tissue remodeling. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. 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.

  3. Core Competence and Education.

    Science.gov (United States)

    Holmes, Gary; Hooper, Nick

    2000-01-01

    Outlines the concept of core competence and applies it to postcompulsory education in the United Kingdom. Adopts an educational perspective that suggests accreditation as the core competence of universities. This economic approach suggests that the market trend toward lifetime learning might best be met by institutions developing a core competence…

  4. Rickettsia parkeri invasion of diverse host cells involves an Arp2/3 complex, WAVE complex and Rho-family GTPase-dependent pathway.

    Science.gov (United States)

    Reed, Shawna C O; Serio, Alisa W; Welch, Matthew D

    2012-04-01

    Rickettsiae are obligate intracellular pathogens that are transmitted to humans by arthropod vectors and cause diseases such as spotted fever and typhus. Although rickettsiae require the host cell actin cytoskeleton for invasion, the cytoskeletal proteins that mediate this process have not been completely described. To identify the host factors important during cell invasion by Rickettsia parkeri, a member of the spotted fever group (SFG), we performed an RNAi screen targeting 105 proteins in Drosophila melanogaster S2R+ cells. The screen identified 21 core proteins important for invasion, including the GTPases Rac1 and Rac2, the WAVE nucleation-promoting factor complex and the Arp2/3 complex. In mammalian cells, including endothelial cells, the natural targets of R. parkeri, the Arp2/3 complex was also crucial for invasion, while requirements for WAVE2 as well as Rho GTPases depended on the particular cell type. We propose that R. parkeri invades S2R+ arthropod cells through a primary pathway leading to actin nucleation, whereas invasion of mammalian endothelial cells occurs via redundant pathways that converge on the host Arp2/3 complex. Our results reveal a key role for the WAVE and Arp2/3 complexes, as well as a higher degree of variation than previously appreciated in actin nucleation pathways activated during Rickettsia invasion. © 2011 Blackwell Publishing Ltd.

  5. 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.

  6. Signaling Rho-kinase mediates inflammation and apoptosis in T cells and renal tubules in cisplatin nephrotoxicity.

    Science.gov (United States)

    Nozaki, Yuji; Kinoshita, Koji; Hino, Shoichi; Yano, Tomohiro; Niki, Kaoru; Hirooka, Yasuaki; Kishimoto, Kazuya; Funauchi, Masanori; Matsumura, Itaru

    2015-04-15

    Nephrotoxicity is a frequent complication of cisplatin-induced chemotherapy, in which T cells are known to promote acute kidney injury (AKI). Apoptosis and necrosis of tubules and inflammatory events also contribute to the nephrotoxicity. A delineation of the mechanisms that underlie the inappropriate renal and tubular inflammation can thus provide important insights into potential therapies for cisplatin-induced AKI. Rho-kinases are known to act as molecular switches controlling several critical cellular functions, including cell migration, cytokine production, and apoptosis. Here, we show that the Rho-kinase inhibitor fasudil attenuated cisplatin nephrotoxicity, resulting in less histological damage, improved renal function, and the infiltration of fewer leukocytes into the kidney. Renal nuclear factor-κB activation and apoptosis were reduced, and the expressions of proinflammatory renal cytokine and chemokine mRNA were decreased. Urinary and renal kidney injury molecule-1 (Kim-1) expression was also reduced, a finding that is consistent with diminished kidney injury. In the current study, we also showed that fasudil could be protective of the impaired tubules. In vitro, fasudil reduced the apoptosis (annexin-V+PI cells) and cytokine production (tumor necrosis factor+ cells) in T cells and the apoptosis (annexin-V+PI cells) and tubular damage (Kim-1+ cells) in proximal tubular cells by flow cytometric analysis. As Rho-kinase plays an important role in promoting cisplatin nephrotoxicity, inhibiting Rho-kinase may be a therapeutic strategy for preventing cisplatin-induced AKI. Copyright © 2015 the American Physiological Society.

  7. 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

    The regulation of adherens junctions (AJs) is critical for multiple events during CNS development, including the formation and maintenance of the neuroepithelium. We have addressed the role of the small GTPase RhoA in the developing mouse nervous system using tissue-specific conditional gene abla...

  8. The inhaled Rho kinase inhibitor Y-27632 protects against allergen-induced acute bronchoconstriction, airway hyperresponsiveness, and inflammation

    NARCIS (Netherlands)

    Schaafsma, Dedmer; Bos, I. Sophie T.; Zuidhof, Annet B.; Zaagsma, Johan; Meurs, Herman

    Recently, we have shown that allergen-induced airway hyperresponsiveness (AHR) after the early (EAR) and late (LAR) asthmatic reaction in guinea pigs could be reversed acutely by inhalation of the Rho kinase inhibitor Y-27632. The present study addresses the effects of pretreatment with inhaled

  9. Effect of Rho-kinase inhibition on complexity of breathing pattern in a guinea pig model of asthma.

    Directory of Open Access Journals (Sweden)

    Saeed Pazhoohan

    Full Text Available Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma.

  10. Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti-melanoma immune response.

    Science.gov (United States)

    Sarrabayrouse, Guillaume; Pich, Christine; Teiti, Iotefa; Tilkin-Mariame, Anne Françoise

    2017-02-15

    Melanoma is a highly lethal cutaneous tumor, killing affected patients through development of multiple poorly immunogenic metastases. Suboptimal activation of immune system by melanoma cells is often due to molecular modifications occurring during tumor progression that prevent efficient recognition of melanoma cells by immune effectors. Statins are HMG-CoA reductase inhibitors, which block the mevalonate synthesis pathway, used by millions of people as hypocholesterolemic agents in cardiovascular and cerebrovascular diseases. They are also known to inhibit Rho GTPase activation and Rho dependent signaling pathways. Rho GTPases are regarded as molecular switches that regulate a wide spectrum of cellular functions and their dysfunction has been characterized in various oncogenic process notably in melanoma progression. Moreover, these molecules can modulate the immune response. Since 10 years we have demonstrated that Statins and other Rho GTPases inhibitors are critical regulators of molecules involved in adaptive and innate anti-melanoma immune response. In this review we summarize our major observations demonstrating that these pharmacological agents stimulate melanoma immunogenicity and suggest a potential use of these molecules to promote anti-melanoma immune response. © 2016 UICC.

  11. 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

  12. Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries

    NARCIS (Netherlands)

    VanBavel, E.; van der Meulen, E. T.; Spaan, J. A.

    2001-01-01

    The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic

  13. Up-regulation of Rho-associated kinase 1/2 by glucocorticoids promotes migration, invasion and metastasis of melanoma.

    Science.gov (United States)

    Huang, Gao-Xiang; Wang, Yan; Su, Jie; Zhou, Peng; Li, Bo; Yin, Li-Juan; Lu, Jian

    2017-12-01

    Although glucocorticoids (GCs) regulate proliferation, differentiation and apoptosis of tumor cells, their influence on metastasis of tumor cells is poorly understood. Melanoma is a type of skin cancers with high metastasis. We investigated the effect of GCs on metastasis of melanoma cells and its mechanism. We found that GCs significantly promoted the adhesion, migration, invasion of melanoma cells in vitro and lung metastasis in experimental melanoma metastasis mice. Dexamethasone (Dex), a synthetic GC, did not change the RhoA, RhoB and RhoC signalings, but significantly increased the expression and activity of Rho-associated kinase 1/2 (ROCK1/2). The effect of Dex was to increase ROCK1/2 stability mediated by glucocorticoid receptor. Inhibiting ROCK1/2 activity with Y-27632, a ROCK1/2 inhibitor abrogated the pro-migration and pro-metastasis effects of GCs in vitro and in vivo, indicating that ROCK1/2 mediated the pro-metastasis effects of GCs. Activation of PI3K/AKT also contributed to the pro-migration and pro-invasion effects of Dex partially through up-regulating ROCK1/2 expression. Additionally, Dex also down-regulated the expression of tissue inhibitors of matrix metalloproteinase-2. Taken together, our findings provide new data to understand the possible promoting roles and mechanisms of GCs in melanoma metastasis. Copyright © 2017. Published by Elsevier B.V.

  14. 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.

  15. Up-regulation of Rho/ROCK signaling in sarcoma cells drives invasion and increased generation of protrusive forces

    Czech Academy of Sciences Publication Activity Database

    Rosel, D.; Brabek, J.; Tolde, O.; Mierke, C.T.; Zitterbart, D.P.; Raupach, C.; Bicanova, K.; Kollmannsberger, P.; Pánková, D.; Veselý, Pavel; Folk, P.; Fabry, B.

    2008-01-01

    Roč. 6, č. 9 (2008), s. 1410-1420 ISSN 1541-7786 Institutional research plan: CEZ:AV0Z50520514 Keywords : Rho kinase ROCK * traction force microscopy * ameboid invasion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.533, year: 2008

  16. Reaction of [rho]-hydroxycinnamyl alcohols with transition metal salts. 3, Preparation and NMR characterization of improved DHPS

    Science.gov (United States)

    Lawrence L. Landucci

    2000-01-01

    Dehydropolymerization of [rho]-hydroxycinnamyl alcohols with manganese(III) acetate in either aqueous acetic acid or pyridine resulted in dehydropolymers (DHPs) that more closely approximate the structure of natural lignins than do DHPs produced by enzymic techniques. The 13C NMR spectrum of a "biomimetic" guaiacyl-DHP (G-DHP) from coniferyl alcohol was very...

  17. RhoA Inactivation Prevents Photoreceptor Axon Retraction in an In Vitro Model of Acute Retinal Detachment

    OpenAIRE

    Fontainhas, Aurora Maria; Townes-Anderson, Ellen

    2011-01-01

    Axon retraction by rod cells is an early response to detachment that likely contributes to poor outcomes after reattachment. In mammalian retina, blocking RhoA signaling prevents axon retraction. Effective treatment can occur as much as 6 hours after the detachment.

  18. β3-Adrenoceptor-mediated relaxation of rat and human urinary bladder : roles of BKCa channels and Rho kinase

    NARCIS (Netherlands)

    Cernecka, Hana; Kersten, Kim; Maarsingh, Harm; Elzinga, Carolina R.; de Jong, Igle Jan; Korstanje, Cees; Michel, Martin C.; Schmidt, Martina

    Previous studies suggest that the large-conductance Ca2+-activated K+ (BKCa) channel and Rho-kinase play major roles in the control of urinary bladder tone. Here, we investigated their involvement in beta-adrenoceptor (AR)-mediated relaxation of rat and human bladder. Concentration-response curves

  19. Crystallization and preliminary X-ray analysis of Psu, an inhibitor of the bacterial transcription terminator Rho

    International Nuclear Information System (INIS)

    Khamrui, Susmita; Ranjan, Amitabh; Pani, Bibhusita; Sen, Ranjan; Sen, Udayaditya

    2010-01-01

    Psu, a unique 21 kDa protein from bacteriophage P4, is a non-essential capsid-decoration protein that inhibits Rho-dependent termination specifically and efficiently both in vivo and in vitro. Psu has been crystallized using PEG as precipitant and the crystals diffracted to 2.3 Å resolution. Psu, a coat protein from bacteriophage P4, inhibits Rho-dependent transcription termination both in vivo and in vitro. The Psu protein is α-helical in nature and appeared to be a dimer in solution. It interacts with Rho and affects the ATP binding and RNA-dependent ATPase activity of Rho, which in turn reduces the rate of RNA release from the elongation complex. Crystals of Psu were grown in space group I422 in the presence of PEG, with unit-cell parameters a = b = 148.76, c = 63.38 Å and a calculated Matthews coefficient of 2.1 Å 3 Da −1 (41.5% solvent content), assuming the presence of two molecules in the asymmetric unit. A native data set was collected to 2.3 Å resolution

  20. p120-catenin differentially regulates cell migration by Rho-dependent intracellular and secreted signals

    DEFF Research Database (Denmark)

    Epifano, Carolina; Megias, Diego; Perez-Moreno, Mirna

    2014-01-01

    The adherens junction protein p120-catenin is implicated in the regulation of cadherin stability, cell migration and inflammatory responses in mammalian epithelial tissues. How these events are coordinated to promote wound repair is not understood. We show that p120 catenin regulates the intrinsic...... migratory properties of primary mouse keratinocytes, but also influences the migratory behavior of neighboring cells by secreted signals. These events are rooted in the ability of p120-catenin to regulate RhoA GTPase activity, which leads to a two-tiered control of cell migration. One restrains cell...... motility via an increase in actin stress fibers, reduction in integrin turnover and an increase in the robustness of focal adhesions. The other is coupled to the secretion of inflammatory cytokines including interleukin-24, which causally enhances randomized cell movements. Taken together, our results...

  1. Rho meson self-energy and dielectron emissivity in an isospin-asymmetric pion medium

    International Nuclear Information System (INIS)

    Gulamov, T.I.; Titov, A.I.; Forschungszentrum Rossendorf e.V.; Kaempfer, B.; Technische Univ., Dresden

    1995-06-01

    The ρ meson self-energy in an isospin asymmetric pion gas at finite temperature and charged-pion chemical potential is evaluated. We utilize a conventional effective π-ρ Lagrangian and the functional integral representation of the partition function in the second order in the ρππ coupling constant. We analyze the gauge invariant rho meson polarization operator and its dependence on the invariant mass M and spatial momentum vertical stroke pvertical stroke of the ρ meson. The pole positions and the values of the imaginary parts of the self-energy for different polarization states have different functional dependences on M and vertical stroke pvertical stroke . The corresponding dielectron rate (calculated from the imaginary part of the polarization operators) shows a distinctive asymmetry when the momentum t=p + -p - is perpendicular or parallel to p, where p ± are the momenta of the electron pair. (orig.)

  2. Colossal thermoelectric power factor in K7/8RhO2

    KAUST Repository

    Saeed, Yasir

    2012-04-12

    The thermoelectric properties of the layered oxides KxRhO 2 (x = 1/2 and 7/8) are investigated by means of the electronic structure, as determined by ab inito calculations and Boltzmann transport theory. In general, the electronic structure of K xRhO 2 is similar to Na xCoO 2, but with strongly enhanced transport. K 7/8RhO 2 exceeds the ultrahigh power factor of Na 0.88CoO 2 reported previously by more than 50%. The roles of the cation concentration and the lattice parameters in the transport properties in this class of compounds are explained. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. IRAS observations of dust heating and energy balance in the Rho Ophiuchi dark cloud

    Science.gov (United States)

    Greene, Thomas P.; Young, Erick T.

    1989-01-01

    The equilibrium process dust emission in the Rho Ophiuchi dark cloud is studied. The luminosity of the cloud is found to closely match the luminosity of the clouds's known embedded and external radiation sources. There is no evidence for a large population of undetected low-luminosity sources within the cloud and unknown external heating is also only a minor source of energy. Most of the cloud's luminosity is emitted in the mid-to-far-IR. Dust temperature maps indicate that the dust is not hot enough to heat the gas to observed temperatures. A simple cloud model with a radiation field composed of flux HD 147889, S1, and Sco OB2 associations predicts the observed IRAS 60 to 100 micron in-band flux ratios for a mean cloud density n(H2) = 1400. Flattened 12 and 25 micron observations show much extended emission in these bands, suggesting stochastic heating of very small grains or large molecules.

  4. On the evaluation of the correction factor μ (rho', tau') for the periodic pulse method

    International Nuclear Information System (INIS)

    Mueller, J.W.

    1976-01-01

    The inconveniences associated with the purely numerical approach we have chosen to solve some of the problems which arise in connection with the source-pulser method are twofold. On the one hand, there is the trouble of calculating the tables for μ, requiring several nights of computer time. On the other hand, apart from some simple limiting values as μ = 1 for tau' = 0 or 1, μ = 1/0.5 + /0.5 - tau'/ for rho' → 0 (and 0 > 1, no appropriate analytical form for the correction factor μ of sufficient precision is known for the moment. This drawback, we hope, is partly removed by a tabulation which should cover the whole region of practical interest. The computer programs for both the evaluation of μ and the Monte Carlo simulation are available upon request

  5. Rho-kinase inhibitors augment the inhibitory effect of propofol on rat bronchial smooth muscle contraction.

    Science.gov (United States)

    Hanazaki, Motohiko; Yokoyama, Masataka; Morita, Kiyoshi; Kohjitani, Atsushi; Sakai, Hiroyasu; Chiba, Yoshihiko; Misawa, Miwa

    2008-06-01

    Airway smooth muscle contraction is not caused by the increase in intracellular Ca(2+) ([Ca(2+)](i)) alone because agonist stimulation increases tension at the same [Ca(2+)](i) (increase in Ca(2+) sensitivity). The small G protein Rho A and Rho-kinase (ROCK) play important roles in the regulation of Ca(2+) sensitivity. In this study, we investigated the effects of three ROCK inhibitors (fasudil, Y-27632, and H-1152) on rat airway smooth muscle contraction and the effects of ROCK inhibitors on propofol-induced bronchodilatory effects. Ring strips from intrapulmonary bronchus of male Wistar rats were placed in 400-microL organ baths containing Krebs-Henseleit solution. After obtaining stable contraction with 30 microM acetylcholine, (1) propofol (1 microM-1 mM) was cumulatively applied; (2) cumulative doses of Y-27632 (0.01-300 microM), fasudil (0.01-100 microM), or H-1152 (0.01-100 microM) were applied; (3) propofol (1 microM-1 mM), with Y-27632, fasudil or H-1152 (0.03 microM or 0.1 microM), was cumulatively applied. (1) Propofol produced concentration-dependent relaxation of rat bronchial smooth muscle. (2) All ROCK inhibitors produced concentration-dependent relaxation. (3) 0.03 microM Y-27632 and fasudil had no significant effect on the concentration-response curve for propofol, while 0.1 microM of both agents significantly shifted concentration-response curves to the left and decreased EC(50). H-1152 (both 0.03 microM and 0.1 microM) significantly sifted the concentration-response curve for propofol to the left and decreased EC(50). ROCK inhibitors, especially H-1152, can attenuate the contraction of rat airway smooth muscle. The combined use of ROCK inhibitors and propofol causes greater relaxation.

  6. Rho-kinase inhibition improves vasodilator responsiveness during hyperinsulinemia in the metabolic syndrome.

    Science.gov (United States)

    Schinzari, Francesca; Tesauro, Manfredi; Rovella, Valentina; Di Daniele, Nicola; Gentileschi, Paolo; Mores, Nadia; Campia, Umberto; Cardillo, Carmine

    2012-09-15

    In patients with the metabolic syndrome (MetS), the facilitatory effect of insulin on forearm vasodilator responsiveness to different stimuli is impaired. Whether the RhoA/Rho kinase (ROCK) pathway is involved in this abnormality is unknown. We tested the hypotheses that, in MetS patients, ROCK inhibition with fasudil restores insulin-stimulated vasodilator reactivity and that oxidative stress plays a role in this mechanism. Endothelium-dependent and -independent forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, were assessed in MetS patients (n = 8) and healthy controls (n = 5) before and after the addition of fasudil (200 μg/min) to an intra-arterial infusion of insulin (0.1 mU/kg/min). In MetS patients (n = 5), fasudil was also infused without hyperinsulinemia. The possible involvement of oxidative stress in the effect of fasudil during hyperinsulinemia was investigated in MetS patients (n = 5) by infusing vitamin C (25 mg/min). In MetS patients, compared with saline, fasudil enhanced endothelium-dependent and -independent vasodilator responses during insulin infusion (P < 0.001 and P = 0.008, respectively), but not in the absence of hyperinsulinemia (P = 0.25 and P = 0.13, respectively). By contrast, fasudil did not affect vasoreactivity to ACh and SNP during hyperinsulinemia in controls (P = 0.11 and P = 0.56, respectively). In MetS patients, fasudil added to insulin and vitamin C did not further enhance vasodilation to ACh and SNP (P = 0.15 and P = 0.43, respectively). In the forearm circulation of patients with the MetS, ROCK inhibition by fasudil improves endothelium-dependent and -independent vasodilator responsiveness during hyperinsulinemia; increased oxidative stress seems to be involved in the pathophysiology of this phenomenon.

  7. Rho kinase inhibitor fasudil mitigates high-cholesterol diet-induced hypercholesterolemia and vascular damage.

    Science.gov (United States)

    Abdali, Nibrass Taher; Yaseen, Awny H; Said, Eman; Ibrahim, Tarek M

    2017-04-01

    The current study was designed to investigate the potential beneficial therapeutic outcome of Rho kinase inhibitor (fasudil) against hypercholesterolemia-induced myocardial and vascular injury in rabbits together with diet modification. Sixteen male rabbits were randomly divided into four groups: normal control group which received standard rabbit chow, hypercholesterolemic control group, and treated groups which received cholesterol-rich rabbit chow (1.5% cholesterol) for 8 weeks. Treated groups received either fasudil (100 mg/kg/day) or rosuvastatin (2.5 mg/kg/day) starting from the ninth week for further 4 weeks with interruption of the cholesterol-rich chow. Biochemical assessment of serum cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and myocardial oxidative/antioxidant biomarkers malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH), besides biochemical assessment of serum nitric oxide (NO), creatine kinase (CK), and lactate dehydrogenase (LDH) activities and serum total antioxidant capacity (TAC), was conducted. Serum vascular cell adhesion molecule 1 (VCAM-1) and serum Rho-associated protein kinase 1 (ROCK-1) were also evaluated along with histopathological examination of aorta specimens. Fasudil administration significantly decreased serum cholesterol, triglyceride (TG), and LDL and significantly increased serum HDL, with concomitant decrease in serum CK and LDH activities, NO, and restoration of serum TAC. Myocardial MDA significantly declined; SOD activity and GSH contents were restored. Serum ROCK-1 and VCAM-1 levels significantly declined as well. Vascular improvement was confirmed with histopathological examination, which revealed normal aortic intema with the absence of atheromas. Fasudil has promising anti-atherogenic activity mediated primarily via alleviation of hypercholesterolemia-induced oxidative stress and modulation of inflammatory response.

  8. Cyclic stretch-induced stress fiber dynamics - Dependence on strain rate, Rho-kinase and MLCK

    International Nuclear Information System (INIS)

    Lee, Chin-Fu; Haase, Candice; Deguchi, Shinji; Kaunas, Roland

    2010-01-01

    Research highlights: → Cyclic stretch induces stress fiber disassembly, reassembly and fusion perpendicular to the direction of stretch. → Stress fiber disassembly and reorientation were not induced at low stretch frequency. → Stretch caused actin fiber formation parallel to stretch in distinct locations in cells treated with Rho-kinase and MLCK inhibitors. -- Abstract: Stress fiber realignment is an important adaptive response to cyclic stretch for nonmuscle cells, but the mechanism by which such reorganization occurs is not known. By analyzing stress fiber dynamics using live cell microscopy, we revealed that stress fiber reorientation perpendicular to the direction of cyclic uniaxial stretching at 1 Hz did not involve disassembly of the stress fiber distal ends located at focal adhesion sites. Instead, these distal ends were often used to assemble new stress fibers oriented progressively further away from the direction of stretch. Stress fiber disassembly and reorientation were not induced when the frequency of stretch was decreased to 0.01 Hz, however. Treatment with the Rho-kinase inhibitor (Y27632) reduced stress fibers to thin fibers located in the cell periphery which bundled together to form thick fibers oriented parallel to the direction of stretching at 1 Hz. In contrast, these thin fibers remained diffuse in cells subjected to stretch at 0.01 Hz. Cyclic stretch at 1 Hz also induced actin fiber formation parallel to the direction of stretch in cells treated with the myosin light chain kinase (MLCK) inhibitor ML-7, but these fibers were located centrally rather than peripherally. These results shed new light on the mechanism by which stress fibers reorient in response to cyclic stretch in different regions of the actin cytoskeleton.

  9. An ELMO2-RhoG-ILK network modulates microtubule dynamics.

    Science.gov (United States)

    Jackson, Bradley C; Ivanova, Iordanka A; Dagnino, Lina

    2015-07-15

    ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting β1 integrin-dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3β, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca(2+)-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes. © 2015 Jackson et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Core stability exercise principles.

    Science.gov (United States)

    Akuthota, Venu; Ferreiro, Andrea; Moore, Tamara; Fredericson, Michael

    2008-02-01

    Core stability is essential for proper load balance within the spine, pelvis, and kinetic chain. The so-called core is the group of trunk muscles that surround the spine and abdominal viscera. Abdominal, gluteal, hip girdle, paraspinal, and other muscles work in concert to provide spinal stability. Core stability and its motor control have been shown to be imperative for initiation of functional limb movements, as needed in athletics. Sports medicine practitioners use core strengthening techniques to improve performance and prevent injury. Core strengthening, often called lumbar stabilization, also has been used as a therapeutic exercise treatment regimen for low back pain conditions. This article summarizes the anatomy of the core, the progression of core strengthening, the available evidence for its theoretical construct, and its efficacy in musculoskeletal conditions.

  11. 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.

  12. Fibroblast activation protein (FAP is essential for the migration of bone marrow mesenchymal stem cells through RhoA activation.

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    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.

  13. The protective effect of Rho-associated kinase inhibitor on aluminum-induced neurotoxicity in rat cortical neurons.

    Science.gov (United States)

    Chen, Tsan-Ju; Hung, Hui-Shan; Wang, Dean-Chuan; Chen, Shun-Sheng

    2010-07-01

    Aluminum (Al) is a neurotoxicant and is implicated in several neurodegenerative diseases, including Alzheimer's disease (AD). In AD brains, one of the pathological hallmarks is the extracellular deposition of senile plaques, which are mainly composed of aggregated amyloid-beta (Abeta). Endoproteolysis of the amyloid-beta precursor protein (AbetaPP) by the beta-secretase and the gamma-secretase generates Abeta. AbetaPP can also be cleaved by the alpha-secretase within the Abeta region, which releases a soluble fragment sAPPalpha and precludes the formation of Abeta. Al has been reported to increase the level of Abeta, promote Abeta aggregation, and increase Abeta neurotoxicity. In contrast, small G protein Rho and its effector, Rho-associated kinase (ROCK), are known to negatively regulate the amount of Abeta. Inhibition of the Rho-ROCK pathway may underlie the ability of nonsteroidal anti-inflammatory drugs and statins to reduce Abeta production. Whether the Rho-ROCK pathway is involved in Al-induced elevation and aggregation of Abeta is unknown. In the present study, cultured rat cortical neurons were treated with Al(malt)(3) in the absence or presence of ROCK inhibitor Y-27632. After the treatment of Al(malt)(3), the cell viability and the level of sAPPalpha were reduced, whereas the amyloid fibrils in the conditioned media were increased. Treatment with Y-27632 prevented these adverse effects of Al(malt)(3) and thus maintained neuronal survival. These results reveal that the activation of the Rho-ROCK signaling pathway was involved in Al-induced effects in terms of the cell viability, the production of sAPPalpha, and the formation of amyloid fibril, which provides a novel mechanism underlying Al-induced neurotoxicity.

  14. The small GTPase RhoU lays downstream of JAK/STAT signaling and mediates cell migration in multiple myeloma.

    Science.gov (United States)

    Canovas Nunes, Sara; Manzoni, Martina; Pizzi, Marco; Mandato, Elisa; Carrino, Marilena; Quotti Tubi, Laura; Zambello, Renato; Adami, Fausto; Visentin, Andrea; Barilà, Gregorio; Trentin, Livio; Manni, Sabrina; Neri, Antonino; Semenzato, Gianpietro; Piazza, Francesco

    2018-02-13

    Multiple myeloma is a post-germinal center B-cell neoplasm, characterized by the proliferation of malignant bone marrow plasma cells, whose survival and proliferation is sustained by growth factors and cytokines present in the bone marrow microenvironment. Among them, IL-6 triggers the signal downstream of its receptor, leading to the activation of the JAK/STAT pathway. The atypical GTPase RhoU lays downstream of STAT3 transcription factor and could be responsible for mediating its effects on cytoskeleton dynamics. Here we demonstrate that RHOU is heterogeneously expressed in primary multiple myeloma cells and significantly modulated with disease progression. At the mRNA level, RHOU expression in myeloma patients correlated with the expression of STAT3 and its targets MIR21 and SOCS3. Also, IL-6 stimulation of human myeloma cell lines up-regulated RHOU through STAT3 activation. On the other hand, RhoU silencing led to a decrease in cell migration with the accumulation of actin stress fibers, together with a decrease in cyclin D2 expression and in cell cycle progression. Furthermore, we found that even though lenalidomide positively regulated RhoU expression leading to higher cell migration rates, it actually led to cell cycle arrest probably through a p21 dependent mechanism. Lenalidomide treatment in combination with RhoU silencing determined a loss of cytoskeletal organization inhibiting cell migration, and a further increase in the percentage of cells in a resting phase. These results unravel a role for RhoU not only in regulating the migratory features of malignant plasma cells, but also in controlling cell cycle progression.

  15. The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals.

    Science.gov (United States)

    Fort, Philippe; Blangy, Anne

    2017-06-01

    The dynamics of cell morphology in eukaryotes is largely controlled by small GTPases of the Rho family. Rho GTPases are activated by guanine nucleotide exchange factors (RhoGEFs), of which diffuse B-cell lymphoma (Dbl)-like members form the largest family. Here, we surveyed Dbl-like sequences from 175 eukaryotic genomes and illuminate how the Dbl family evolved in all eukaryotic supergroups. By combining probabilistic phylogenetic approaches and functional domain analysis, we show that the human Dbl-like family is made of 71 members, structured into 20 subfamilies. The 71 members were already present in ancestral jawed vertebrates, but several members were subsequently lost in specific clades, up to 12% in birds. The jawed vertebrate repertoire was established from two rounds of duplications that occurred between tunicates, cyclostomes, and jawed vertebrates. Duplicated members showed distinct tissue distributions, conserved at least in Amniotes. All 20 subfamilies have members in Deuterostomes and Protostomes. Nineteen subfamilies are present in Porifera, the first phylum that diverged in Metazoa, 14 in Choanoflagellida and Filasterea, single-celled organisms closely related to Metazoa and three in Fungi, the sister clade to Metazoa. Other eukaryotic supergroups show an extraordinary variability of Dbl-like repertoires as a result of repeated and independent gain and loss events. Last, we observed that in Metazoa, the number of Dbl-like RhoGEFs varies in proportion of cell signaling complexity. Overall, our analysis supports the conclusion that Dbl-like RhoGEFs were present at the origin of eukaryotes and evolved as highly adaptive cell signaling mediators. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  16. Low molecular weight protein tyrosine phosphatase isoforms regulate breast cancer cells migration through a RhoA dependent mechanism.

    Science.gov (United States)

    Alho, Irina; Costa, Luis; Bicho, Manuel; Coelho, Constança

    2013-01-01

    Low molecular weight protein tyrosine phosphatase (LMW-PTP) has been associated with cell proliferation control through dephosphorylation and inactivation of growth factor receptors such as PDGF-R and EphA2, and with cellular adhesion and migration through p190RhoGap and RhoA. We aim to clarify the role of two main LMW-PTP isoforms in breast cancer tumorigenesis. We used a siRNA-mediated loss-of-function in MDA-MB-435 breast cancer cell line to study the role of the two main LMW-PTP isoforms, fast and slow, in breast cancer tumorigenesis and migration. Our results show that the siRNAs directed against total LMW-PTP and LMW-PTP slow isoform enhanced cell motility in an invasive breast cancer cell line, MDA-MB-435, with no changes in the proliferation and invasive potential of cells. The total LMW-PTP knockdown caused a more pronounced increase of cell migration. Suppression of total LMW-PTP decreased RhoA activation and suppression of the LMW-PTP slow isoform caused a small but significant increase in RhoA activation. We propose that the increase or decrease in RhoA activation induces changes in stress fibers formation and consequently alter the adhesive and migratory potential of cells. These findings suggest that the two main isoforms of LMW-PTP may act differentially, with the fast isoform having a more prominent role in tumor cell migration. In addition, our results highlight functional specificity among LMW-PTP isoforms, suggesting hitherto unknown roles for these proteins in breast cancer biology. Novel therapeutic approaches targeting LMW-PTP, considering the expression of these two isoforms and not LMW-PTP as a whole, should be investigated.

  17. Effect of chronic perinatal hypoxia on the role of rho-kinase in pulmonary artery contraction in newborn lambs.

    Science.gov (United States)

    Blood, Arlin B; Terry, Michael H; Merritt, Travis A; Papamatheakis, Demosthenes G; Blood, Quintin; Ross, Jonathon M; Power, Gordon G; Longo, Lawrence D; Wilson, Sean M

    2013-01-15

    Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at 3,801 m above sea level during gestation and the first 2 wk of life were compared with those with gestation at low altitude. In vitro studies of isolated pulmonary arterial rings found a more forceful contraction in response to KCl and 5-HT in high-altitude compared with low-altitude lambs. There was no difference between the effects of blockers of various pathways of extracellular Ca(2+) entry in low- and high-altitude arteries. In contrast, inhibition of rho-kinase resulted in significantly greater attenuation of 5-HT constriction in high-altitude compared with low-altitude arteries. High-altitude lambs had higher baseline pulmonary artery pressures and greater elevations in pulmonary artery pressure during 15 min of acute hypoxia compared with low-altitude lambs. Despite evidence for an increased role for rho-kinase in high-altitude arteries, in vivo studies found no significant difference between the effects of rho-kinase inhibition on hypoxic pulmonary vasoconstriction in intact high-altitude and low-altitude lambs. We conclude that chronic hypoxia in utero results in increased vasopressor response to both acute hypoxia and serotonin, but that rho-kinase is involved only in the increased response to serotonin.

  18. Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function.

    Science.gov (United States)

    Duong-Quy, S; Dao, P; Hua-Huy, T; Guilluy, C; Pacaud, P; Dinh-Xuan, A T

    2011-02-01

    Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function. Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought. Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls. Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.

  19. Rho-independent stimulation of axon outgrowth and activation of the ERK and Akt signaling pathways by C3 transferase in sensory neurons

    Directory of Open Access Journals (Sweden)

    Maria eAuer

    2012-10-01

    Full Text Available Peripheral nerve injury triggers the activation of RhoA in spinal motor and peripheral sensory neurons. RhoA activates a number of effector proteins including the Rho-associated kinase, ROCK, which targets the cytoskeleton and leads to inhibition of neurite outgrowth. Blockade of the Rho/ROCK pathway by pharmacological means improves axon regeneration after experimental injury. C3bot transferase, an exoenzyme produced by Clostridium botulinum, inactivates RhoA by ADP-ribosylation. Up to now it was not investigated thoroughly whether C3bot exerts positive effects on peripheral axon regeneration as well. In the present study, recombinant membrane permeable C3bot produced a small, but significant, axon outgrowth effect on peripheral sensory neurons dissociated from adult dorsal root ganglia of the rat. Neuronal overexpression of C3, however, did not enhance axonal growth. Moreover, transfection of plasmids encoding dominant negative RhoA or RhoA specific shRNAs failed to increase axonal growth. Furthermore, we show that the C3bot mutant, C3E174Q, which lacks RhoA inhibitory activity, still stimulates axonal growth. When analyzing possible signaling mechanisms we found that ERK (extracellular signal-regulated kinase and Akt are activated by C3bot and ERK is induced by the C3E174Q mutant. Upregulation of kinase activities by C3bot occurs significantly faster than inactivation of RhoA indicating a RhoA-independent pathway of action by C3bot. The induction of ERK signaling by C3bot was detected in embryonic hippocampal neurons, too. Taken together, although RhoA plays a central role for inhibition of axon outgrowth by myelin-derived inhibitors, it does not interfere with axonal growth of sensory neurons on a permissive substrate in vitro. C3bot blocks neuronal RhoA activity, but its positive effects on axon elongation and branching appear to be mediated by Rho independent mechanisms involving activation of axon growth promoting ERK and Akt kinases.

  20. 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.

  1. 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.)

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

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    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.

  3. Acetylsalicylic acid regulates overexpressed small GTPase RhoA in vascular smooth muscle cells through prevention of new synthesis and enhancement of protein degradation.

    Science.gov (United States)

    Li, Dong-Bo; Fu, Zhi-Xuan; Ruan, Shu-Qin; Hu, Shen-Jiang; Li, Xia

    2012-04-01

    RhoA has been shown to play a major role in vascular processes and acetylsalicylic acid (aspirin) is known to exert a cytoprotective effect via multiple mechanisms. In the present study, we aimed at investigating the effect of aspirin on RhoA expression under a stress state in rat VSMCs (vascular smooth muscle cells) and the underlying mechanisms. The expression of iNOS (inducible nitric oxide synthase) and iNOS activity as well as NO concentration was significantly promoted by LPS (lipopolysaccharide) accompanying the elevation of RhoA expression, which was blocked by the addition of the iNOS inhibitor L-NIL [L-N6-(1-iminoethyl)lysine dihydrochloride]. Aspirin (30 μM) significantly attenuated the elevation of RhoA, while indomethacin and salicylate had no similar effect. The sGC (soluble guanylate cyclase) inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) showed the same effect as aspirin in down-regulating RhoA but was reversed by the addition of the cGMP analogue 8-Br-PET-cGMP (β-phenyl-1,N2-ethano-8-bromoguanosine 3',5'-cyclic monophosphorothioate). 8-Br-PET-cGMP solely enhanced the RhoA expression that was abrogated by preincubation with aspirin. Degradation analysis indicated that aspirin enhanced the protein degradation rate of RhoA and GDP-bound RhoA seemed to be more susceptible to aspirin-enhanced degradation compared with the GTP-bound form. Our results indicate that aspirin attenuates the LPS-induced overexpression of RhoA both by inhibiting new synthesis and accelerating protein degradation, which may help elucidate the multiple beneficial effects of aspirin.

  4. 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

  5. Indole-3-carbinol inhibits MDA-MB-231 breast cancer cell motility and induces stress fibers and focal adhesion formation by activation of Rho kinase activity.

    Science.gov (United States)

    Brew, Christine T; Aronchik, Ida; Kosco, Karena; McCammon, Jasmine; Bjeldanes, Leonard F; Firestone, Gary L

    2009-05-15

    Indole-3-carbinol (I3C), a phytochemical derived from cruciferous vegetables such as broccoli and Brussels sprouts, has potent antiproliferative effects in human breast cancer cells and has been shown to decrease metastatic spread of tumors in experimental animals. Using chemotaxis and fluorescent-bead cell motility assays, we demonstrated that I3C significantly decreased the in vitro migration of MDA-MB-231 cells, a highly invasive breast cancer cell line. Immunofluorescence staining of the actin cytoskeleton revealed that concurrent with the loss of cell motility, I3C treatment significantly increased stress fiber formation. Furthermore, I3C induced the localization of the focal adhesion component vinculin and tyrosine-phosphorylated proteins to the cell periphery, which implicates an indole-dependent enhancement of focal adhesions within the outer boundary of the cells. Coimmunoprecipitation analysis of focal adhesion kinase demonstrated that I3C stimulated the dynamic formation of the focal adhesion protein complex without altering the total level of individual focal adhesion proteins. The RhoA-Rho kinase pathway is involved in stress fiber and focal adhesion formation, and I3C treatment stimulated Rho kinase enzymatic activity and cofilin phosphorylation, which is a downstream target of Rho kinase signaling, but did not increase the level of active GTP-bound RhoA. Exposure of MDA-MB-231 cells to the Rho kinase inhibitor Y-27632, or expression of dominant negative RhoA ablated the I3C induced formation of stress fibers and of peripheral focal adhesions. Expression of constitutively active RhoA mimicked the I3C effects on both processes. Taken together, our data demonstrate that I3C induces stress fibers and peripheral focal adhesions in a Rho kinase-dependent manner that leads to an inhibition of motility in human breast cancer cells. (c) 2008 Wiley-Liss, Inc.

  6. 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.

  7. Nuclear reactor core flow baffling

    International Nuclear Information System (INIS)

    Berringer, R.T.

    1979-01-01

    A flow baffling arrangement is disclosed for the core of a nuclear reactor. A plurality of core formers are aligned with the grids of the core fuel assemblies such that the high pressure drop areas in the core are at the same elevations as the high pressure drop areas about the core periphery. The arrangement minimizes core bypass flow, maintains cooling of the structure surrounding the core, and allows the utilization of alternative beneficial components such as neutron reflectors positioned near the core

  8. Sediment Core Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides instrumentation and expertise for physical and geoacoustic characterization of marine sediments.DESCRIPTION: The multisensor core logger measures...

  9. 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.)

  10. 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

  11. Can Psychiatric Rehabilitation Be Core to CORE?

    Science.gov (United States)

    Olney, Marjorie F.; Gill, Kenneth J.

    2016-01-01

    Purpose: In this article, we seek to determine whether psychiatric rehabilitation principles and practices have been more fully incorporated into the Council on Rehabilitation Education (CORE) standards, the extent to which they are covered in four rehabilitation counseling "foundations" textbooks, and how they are reflected in the…

  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. 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.

  14. Making an Ice Core.

    Science.gov (United States)

    Kopaska-Merkel, David C.

    1995-01-01

    Explains an activity in which students construct a simulated ice core. Materials required include only a freezer, food coloring, a bottle, and water. This hands-on exercise demonstrates how a glacier is formed, how ice cores are studied, and the nature of precision and accuracy in measurement. Suitable for grades three through eight. (Author/PVD)

  15. Multi-core Microprocessors

    Indian Academy of Sciences (India)

    Design cost of multi-core processors is lower than the cost of designing very complex single processors. This is because in a multi-core pro- cessor a simple processor is designed and replicated. The idea of using several independent processors to work simul- taneously and cooperate to execute a single program is quite ...

  16. PWR core design calculations

    International Nuclear Information System (INIS)

    Trkov, A.; Ravnik, M.; Zeleznik, N.

    1992-01-01

    Functional description of the programme package Cord-2 for PWR core design calculations is presented. Programme package is briefly described. Use of the package and calculational procedures for typical core design problems are treated. Comparison of main results with experimental values is presented as part of the verification process. (author) [sl

  17. Multi-core Microprocessors

    Indian Academy of Sciences (India)

    using these transistors and resultant improvement in the process-. Keywords. Moore's law, evolution of multi- core processors, programming multi-core processors. ing speed. Packing more transistors in a chip also enabled de- signers to improve the architecture of microprocessors in many. RESONANCE | December 2017.

  18. Mars' core and magnetism.

    Science.gov (United States)

    Stevenson, D J

    2001-07-12

    The detection of strongly magnetized ancient crust on Mars is one of the most surprising outcomes of recent Mars exploration, and provides important insight about the history and nature of the martian core. The iron-rich core probably formed during the hot accretion of Mars approximately 4.5 billion years ago and subsequently cooled at a rate dictated by the overlying mantle. A core dynamo operated much like Earth's current dynamo, but was probably limited in duration to several hundred million years. The early demise of the dynamo could have arisen through a change in the cooling rate of the mantle, or even a switch in convective style that led to mantle heating. Presently, Mars probably has a liquid, conductive outer core and might have a solid inner core like Earth.

  19. Lunar Core and Tides

    Science.gov (United States)

    Williams, J. G.; Boggs, D. H.; Ratcliff, J. T.

    2004-01-01

    Variations in rotation and orientation of the Moon are sensitive to solid-body tidal dissipation, dissipation due to relative motion at the fluid-core/solid-mantle boundary, and tidal Love number k2 [1,2]. There is weaker sensitivity to flattening of the core-mantle boundary (CMB) [2,3,4] and fluid core moment of inertia [1]. Accurate Lunar Laser Ranging (LLR) measurements of the distance from observatories on the Earth to four retroreflector arrays on the Moon are sensitive to lunar rotation and orientation variations and tidal displacements. Past solutions using the LLR data have given results for dissipation due to solid-body tides and fluid core [1] plus Love number [1-5]. Detection of CMB flattening, which in the past has been marginal but improving [3,4,5], now seems significant. Direct detection of the core moment has not yet been achieved.

  20. Proneural Transcription Factors Regulate Different Steps of Cortical Neuron Migration through Rnd-Mediated Inhibition of RhoA Signaling

    Science.gov (United States)

    Pacary, Emilie; Heng, Julian; Azzarelli, Roberta; Riou, Philippe; Castro, Diogo; Lebel-Potter, Mélanie; Parras, Carlos; Bell, Donald M.; Ridley, Anne J.; Parsons, Maddy; Guillemot, François

    2011-01-01

    Summary Little is known of the intracellular machinery that controls the motility of newborn neurons. We have previously shown that the proneural protein Neurog2 promotes the migration of nascent cortical neurons by inducing the expression of the atypical Rho GTPase Rnd2. Here, we show that another proneural factor, Ascl1, promotes neuronal migration in the cortex through direct regulation of a second Rnd family member, Rnd3. Both Rnd2 and Rnd3 promote neuronal migration by inhibiting RhoA signaling, but they control distinct steps of the migratory process, multipolar to bipolar transition in the intermediate zone and locomotion in the cortical plate, respectively. Interestingly, these divergent functions directly result from the distinct subcellular distributions of the two Rnd proteins. Because Rnd proteins also regulate progenitor divisions and neurite outgrowth, we propose that proneural factors, through spatiotemporal regulation of Rnd proteins, integrate the process of neuronal migration with other events in the neurogenic program. PMID:21435554

  1. 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}.

  2. Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

    DEFF Research Database (Denmark)

    Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli

    2013-01-01

    The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

  3. Study of Branching Ratio And Polarization Fraction in Neutral B Meson Decays to Negative Rho Meson Positive Kaon Resonance

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Baosen; /Wisconsin U., Madison

    2006-03-07

    We present the preliminary results on the search for B{sup 0} {yields} {rho}{sup -}K*{sup +}. The data sample comprises 122.7 million B{bar B} pairs in the e{sup +}e{sup -} annihilation through the {Upsilon}(4S) resonance collected during 1999-2003 with the BABAR detector at the PEP-II asymmetric-energy collider at Stanford Linear Accelerator Center (SLAC). We obtain an upper limit of the branching ratio at 90% confidence level as {Beta}(B{sup 0} {yields} {rho}{sup -}K*{sup +}) < 17.2 x 10{sup -6}. The fitted result on the polarization fraction shows no evidence that the decay is longitudinally dominated as predicted by various theoretical models.

  4. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

    International Nuclear Information System (INIS)

    Fukuda, Hiroki; Nakamura, Seikou; Chisaki, Yugo; Takada, Tetsuya; Toda, Yuki; Murata, Hiroaki; Itoh, Kazuyuki; Yano, Yoshitaka; Takata, Kazuyuki; Ashihara, Eishi

    2016-01-01

    Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.

  5. Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Hiroki [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Nakamura, Seikou [Department of Pharmacognosy, Kyoto Pharmaceutical University, Kyoto (Japan); Chisaki, Yugo [Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto (Japan); Takada, Tetsuya [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Toda, Yuki [Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Murata, Hiroaki [Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Department of Orthopedic Surgery, Matsushita Memorial Hospital, Osaka (Japan); Itoh, Kazuyuki [Department of Biology, Osaka Medical Center of Cancer and Cardiovascular Diseases, Osaka (Japan); Yano, Yoshitaka [Education and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Kyoto (Japan); Takata, Kazuyuki [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan); Ashihara, Eishi, E-mail: ash@mb.kyoto-phu.ac.jp [Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Kyoto (Japan)

    2016-02-26

    Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti-proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non-treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. - Highlights: • Daphnetin, a coumarin-derivative, inhibited invasion and migration of LM8 cells. • Stress fibers and filopodia were decreased by daphnetin treatment. • Daphnetin decreased RhoA and Cdc42 protein expression.

  6. Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1

    Directory of Open Access Journals (Sweden)

    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.

  7. Rotavirus infection of cells in culture induces activation of RhoA and changes in the actin and tubulin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Jose Luis Zambrano

    Full Text Available Rotavirus infection induces an increase in [Ca(2+](cyto, which in turn may affect the distribution of the cytoskeleton proteins in the infected cell. Changes in microfilaments, including the formation of stress fibers, were observed starting at 0.5 h.p.i. using fluorescent phalloidin. Western blot analysis indicated that RhoA is activated between 0.5 and 1 h.p.i. Neither the phosphorylation of RhoA nor the formation of stress fibers were observed in cells infected with virions pre-treated with an anti-VP5* non-neutralizing mAb, suggesting that RhoA activation is stimulated by the interaction of the virus with integrins forming the cell receptor complex. In addition, the structure of the tubulin cytoskeleton was also studied. Alterations of the microtubules were evident starting at 3 h.p.i. and by 7 h.p.i. when microtubules were markedly displaced toward the periphery of the cell cytoplasm. Loading of rotavirus-infected cells with either a Ca(2+ chelator (BAPTA or transfection with siRNAs to silence NSP4, reversed the changes observed in both the microfilaments and microtubules distribution, but not the appearance of stress fibers. These results indicate that alterations in the distribution of actin microfilaments are initiated early during infection by the activation of RhoA, and that latter changes in the Ca(2+ homeostasis promoted by NSP4 during infection may be responsible for other alterations in the actin and tubulin cytoskeleton.

  8. The production of $\\phi , \\omega$ and $\\rho$ mesons in $p$-, $d$-, S- and Pb- induced reactions at the CERN SPS

    CERN Document Server

    Jouan, D; Alessandro, B; Alexa, C; Arnaldi, R; Atayan, M; Baglin, C; Baldit, A; Bedjidian, M; Beolè, S; Boldea, V; Boraldo, P; Borenstein, S R; Borges, G; Bussière, A; Capelli, L; Castanier, C; Castor, J I; Chaurand, B; Cheynis, B; Chiavassa, E; Cicalò, C; Claudino, T; Comets, M P; Constantinescu, S; Cortese, P; Cruz, J; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Espagnon, B; Fargeix, J; Force, P; Gallio, M; Gavrilov, Yu K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grigorian, S; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanian, H R; Hakobyan, R S; Haroutunian, R; Idzik, M; Karavitcheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Macciotta, P; MacCormick, M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prado da Silva, W L; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Rato-Mendes, P; Riccati, L; Romana, A; Santos, H; Saturnini, P; Scalas, E; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, F; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N; Wu, T

    2004-01-01

    From proton, deuteron, S- and Pb-induced reactions, experiments NA38 and NA50 have measured muon pair production with various targets. In particular, the production rates of the phi omega and rho mesons have been simultaneously extracted and compared. Preliminary partial results of the most recent Pb-Pb measurement done in year 2000 by NA50 are presented here. They are also included in the comparison with the results obtained with lighter interacting nuclei. (23 refs).

  9. A Birthday Paradox for Markov chains with an optimal bound for collision in the Pollard Rho algorithm for discrete logarithm

    OpenAIRE

    Kim, Jeong Han; Montenegro, Ravi; Peres, Yuval; Tetali, Prasad

    2010-01-01

    We show a Birthday Paradox for self-intersections of Markov chains with uniform stationary distribution. As an application, we analyze Pollard's Rho algorithm for finding the discrete logarithm in a cyclic group $G$ and find that if the partition in the algorithm is given by a random oracle, then with high probability a collision occurs in $\\Theta(\\sqrt{|G|})$ steps. Moreover, for the parallelized distinguished points algorithm on $J$ processors we find that $\\Theta(\\sqrt{|G|}/J)$ steps suffi...

  10. Physical and genetic interaction between ammonium transporters and the signaling protein Rho1 in the plant pathogen Ustilago maydis.

    Science.gov (United States)

    Paul, Jinny A; Barati, Michelle T; Cooper, Michael; Perlin, Michael H

    2014-10-01

    Dimorphic transitions between yeast-like and filamentous forms occur in many fungi and are often associated with pathogenesis. One of the cues for such a dimorphic switch is the availability of nutrients. Under conditions of nitrogen limitation, fungal cells (such as those of Saccharomyces cerevisiae and Ustilago maydis) switch from budding to pseudohyphal or filamentous growth. Ammonium transporters (AMTs) are responsible for uptake and, in some cases, for sensing the availability of ammonium, a preferred nitrogen source. Homodimer and/or heterodimer formation may be required for regulating the activity of the AMTs. To investigate the potential interactions of Ump1 and Ump2, the AMTs of the maize pathogen U. maydis, we first used the split-ubiquitin system, followed by a modified split-YFP (yellow fluorescent protein) system, to validate the interactions in vivo. This analysis showed the formation of homo- and hetero-oligomers by Ump1 and Ump2. We also demonstrated the interaction of the high-affinity ammonium transporter, Ump2, with the Rho1 GTPase, a central protein in signaling, with roles in controlling polarized growth. This is the first demonstration in eukaryotes of the physical interaction in vivo of an ammonium transporter with the signaling protein Rho1. Moreover, the Ump proteins interact with Rho1 during the growth of cells in low ammonium concentrations, a condition required for the expression of the Umps. Based on these results and the genetic evidence for the interaction of Ump2 with both Rho1 and Rac1, another small GTPase, we propose a model for the role of these interactions in controlling filamentation, a fundamental aspect of development and pathogenesis in U. maydis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  11. Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

    Directory of Open Access Journals (Sweden)

    Roman J Krawetz

    Full Text Available The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the

  12. Assessment of the Activation State of Rho Family GTP-Binding Proteins in Breast Cancer Cells and Specimens

    Science.gov (United States)

    2004-08-01

    04.00+0 DOI: 10.1128/MCB.21.5.1463-1474.2001 Copyright © 2001, American Society for Microbiology . All Rights Reserved. Autoinhibition Mechanism of...Tennessee Health Science Center, Memphis, Tennessee 38163,’ and Laboratorio di Bioligia Molecolare, Istituto G. Gaslini, 16148 Genoa, Italy 2 Received 29...American Society for Microbiology . All Rights Reserved. Involvement of Rho Family GTPases in pl9Arf- and p53-Mediated Proliferation of Primary Mouse

  13. Tilt - ellips and rho - phase modelling of VLF EM and VLF R in Candi Umbul Magelang

    Science.gov (United States)

    Affanti, Adella Putri; Niasari, Sintia Windhi

    2017-07-01

    A research for geothermal energy is increased due to the need of green energy. The presence of geothermal manifestations indicate the existence of geothermal system. One of the geothermal manifestations is warm spring. CandiUmbul area which located in Telomoyo, Magelang has warm spring as the geothermal manifestation. Very Low Frequency (VLF) is one of geophysical method that can be used to map the subsurface in Candi Umbul, Telomoyo. VLF is a method using electromagnetic field that powered and transferred by the transmitter. The receiver read the electromagnetic signal which induce the rock and give information about the conductivity as the physical property measurred. In this research, after collecting and processing data, we modeled tilt-ellips data of VLF-EM and rho-phase data of VLF-R to explain the geothermal system of Candi Umbul. Both VLF-EM and VLF-R model were correlated for the interpretation. The model showed an anomalous conductive feature beneath the research area. The result of this research showed that the anomaly is oriented in NW-SE direction. This direction is assumed as a fluid path way of Candi Umbul which became the outflow of Telomoyo geothermal system. To prove the early deduction this research is still on going.

  14. Involvement of Histamine and RhoA/ROCK in Penicillin Immediate Hypersensitivity Reactions.

    Science.gov (United States)

    Han, Jiayin; Yi, Yan; Li, Chunying; Zhang, Yushi; Wang, Lianmei; Zhao, Yong; Pan, Chen; Liang, Aihua

    2016-09-13

    The mechanism of penicillin immediate hypersensitivity reactions has not been completely elucidated. These reactions are generally considered to be mediated by IgE, but penicillin-specific IgE could not be detected in most cases. This study demonstrated that penicillin was able to cause vascular hyperpermeability in a mouse model mimicking clinical symptoms of penicillin immediate hypersensitivity reactions. The first exposure to penicillin also induced immediate edema and exudative reactions in ears and lungs of mice in a dose-dependent manner. Vasodilation was noted in microvessels in ears. These reactions were unlikely to be immune-mediated reactions, because no penicillin-specific IgE was produced. Furthermore, penicillin treatment directly elicited rapid histamine release. Penicillin also led to F-actin reorganization in human umbilical vein endothelial cells and increased the permeability of the endothelial monolayer. Activation of the RhoA/ROCK signaling pathway was observed in ears and lungs of mice and in endothelial cells after treatment with penicillin. Both an anti-histamine agent and a ROCK inhibitor attenuated penicillin immediate hypersensitivity reactions in mice. This study presents a novel mechanism of penicillin immediate hypersensitivity reactions and suggests a potential preventive approach against these reactions.

  15. Differentiation of brain tumor-related edema based on 3D T1rho imaging.

    Science.gov (United States)

    Villanueva-Meyer, J E; Barajas, R F; Mabray, M C; Chen, W; Shankaranarayanan, A; Koon, P; Barani, I J; Tihan, T; Cha, S

    2017-06-01

    Cerebral edema associated with brain tumors is an important source of morbidity. Its type depends largely on the capillary ultra-structures of the histopathologic subtype of underlying brain tumor. The purpose of our study was to differentiate vasogenic edema associated with brain metastases and infiltrative edema related to diffuse gliomas using quantitative 3D T1 rho (T1ρ) imaging. Preoperative MR examination including whole brain 3D T1ρ imaging was performed in 23 patients with newly diagnosed brain tumors (9 with metastasis, 8 with lower grade glioma, LGG, 6 with glioblastoma, GBM). Mean T1ρ values were measured in regions of peritumoral non-enhancing T2 signal hyperintensity, excluding both enhancing and necrotic or cystic component, and normal-appearing white matter. Mean T1ρ values were significantly elevated in the vasogenic edema surrounding intracranial metastases when compared to the infiltrative edema associated with either LGG or GBM (p=0.02 and <0.01, respectively). No significant difference was noted between T1ρ values of infiltrative edema between LGG and GBM (p=0.84 and 0.96, respectively). Our study demonstrates the feasibility and potential diagnostic role of T1ρ in the quantitative differentiation between edema related to intracranial metastases and gliomas and as a potentially complementary tool to standard MR techniques in further characterizing pathophysiology of vasogenic and infiltrative edema. Copyright © 2017. Published by Elsevier B.V.

  16. Neurite outgrowth resistance to rho kinase inhibitors in PC12 Adh cell.

    Science.gov (United States)

    Yin, Hua; Hou, Xiaolin; Tao, Tingrui; Lv, Xiaoman; Zhang, Luyong; Duan, Weigang

    2015-05-01

    Rho kinase (ROCK) inhibitor is a promising agent for neural injury disorders, which mechanism is associated with neurite outgrowth. However, neurite outgrowth resistance occurred when PC12 Adh cell was treated with ROCK inhibitors for a longer time. PC12 Adh cells were treated with ROCK inhibitor Y27632 or NGF for different durations. Neurite outgrowth resistance occurred when PC12 Adh cell exposed to Y27632 (33 µM) for 3 or more days, but not happen when exposed to nerve growth factor (NGF, 100 ng/mL). The gene expression in the PC12 Adh cells treated with Y27632 (33 µM) or NGF (100 ng/mL) for 2 or 4 days was assayed by gene microarray, and the reliability of the results were confirmed by real-time RT-PCR. Cluster analysis proved that the gene expression profile of PC12 Adh cell treated with Y27632 for 4 days was different from that treated with Y27632 for 2 days and those treated with NGF for 2 and 4 days, respectively. Pathway analysis hinted that the neurite outgrowth resistance could be associated with up-regulation of inflammatory pathways, especially rno04610 (complement and coagulation cascades), and down-regulation of cell cycle pathways, especially rno04110. © 2015 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  17. Long-term culture of human odontoma-derived cells with a Rho kinase inhibitor.

    Science.gov (United States)

    Uzawa, Katsuhiro; Kasamatsu, Atsushi; Saito, Tomoaki; Takahara, Toshikazu; Minakawa, Yasuyuki; Koike, Kazuyuki; Yamatoji, Masanobu; Nakashima, Dai; Higo, Morihiro; Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki

    2016-09-10

    Because of cellular senescence/apoptosis, no effective culture systems are available to maintain replication of cells from odontogenic tumors especially for odontoma, and, thus, the ability to isolate human odontoma-derived cells (hODCs) for functional studies is needed. The current study was undertaken to develop an approach to isolate hODCs and fully characterize the cells in vitro. The hODCs were cultured successfully with a Rho-associated protein kinase inhibitor (Y-27632) for an extended period with stabilized lengths of the telomeres to sustain a similar phenotype/property as the primary tumoral cells. While the hODCs showed stable long-term expansion with expression of major dental epithelial markers including dentin sialophosphoprotein (DSPP) even in the three-dimensional microenvironment, they lack the specific markers for the characteristics of stem cells. Moreover, cells from dental pulp showed significant up-regulation of DSPP when co-cultured with the hODCs, while control fibroblasts with the hODCs did not. Taken together, we propose that the hODCs can be isolated and expanded over the long term with Y-27632 to investigate not only the development of the hODCs but also other types of benign human tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Crosstalk between Substrates and Rho-Associated Kinase Inhibitors in Cryopreservation of Tissue-Engineered Constructs

    Directory of Open Access Journals (Sweden)

    Arindam Bit

    2017-01-01

    Full Text Available It is documented that human mesenchymal stem cells (hMSCs can be differentiated into various types of cells to present a tool for tissue engineering and regenerative medicine. Thus, the preservation of stem cells is a crucial factor for their effective long-term storage that further facilitates their continuous supply and transportation for application in regenerative medicine. Cryopreservation is the most important, practicable, and the only established mechanism for long-term preservation of cells, tissues, and organs, and engineered tissues; thus, it is the key step for the improvement of tissue engineering. A significant portion of MSCs loses cellular viability while freeze-thawing, which represents an important technical limitation to achieving sufficient viable cell numbers for maximum efficacy. Several natural and synthetic materials are extensively used as substrates for tissue engineering constructs and cryopreservation because they promote cell attachment and proliferation. Rho-associated kinase (ROCK inhibitors can improve the physiological function and postthaw viability of cryopreserved MSCs. This review proposes a crosstalk between substrate topology and interaction of cells with ROCK inhibitors. It is shown that incorporation of ionic nanoparticles in the presence of an external electrical field improves the generation of ROCK inhibitors to safeguard cellular viability for the enhanced cryopreservation of engineered tissues.

  19. Effects of Brown-Rho scalings in nuclear matter, neutron stars and finite nuclei

    Science.gov (United States)

    Kuo, T. T. S.; Dong, Huan

    2011-01-01

    We have carried out calculations for nuclear matter, neutron stars and finite nuclei using NN potentials with and without the medium-dependent modifications based on the Brown-Rho (BR) scalings. Using the Vlow-k low-momentum interactions derived from such potentials, the equations of state (EOS) for symmetric and asymmetric nuclear matter, for densities up to ~ 5ρ0, are calculated using a RPA method where the particle-particle hole-hole ring diagrams are summed to all orders. The medium effects from both a linear BR scaling (BR1) and a non-linear one (BR2) are considered, and they both are essential for our EOSs to reproduce the nuclear matter saturation properties. For densities ρ below ρ0, results from BR1 and BR2 are close to each other. For higher densities, the EOS given by BR2 is more desirable and is well reproduced by that given by the interaction (Vlow-k+TBF) where Vlow-k is the unsealed low-momentum interaction and TBF is an empirical Skyrme three-body force. The moment of inertia of neutron stars is ~ 60 and ~ 25Modotkm2 respectively with and without the inclusion of the above BR2 medium effects. Effects from the BR scaling are important for the long half-life, ~ 5000yrs, of the 14C - 14N β-decay.

  20. Association of Rho-kinase Gene Polymorphisms with Respiratory Distress Syndrome in Preterm Neonates.

    Science.gov (United States)

    Kaya, Gül; Sivasli, Ercan; Oztuzcu, Serdar; Melekoglu, Nuriye A; Ozkara, Esma; Sarikabadayi, Unal; Demiryürek, Abdullah T

    2017-02-01

    Respiratory distress syndrome (RDS) of the newborn is one of the most common causes of morbidity and mortality in preterm infants. Our objective was to determine the association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and RDS in preterm neonates. A total of 193 preterm infants with RDS and 186 preterm infants without respiratory problems were included in this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. We observed that ROCK1 gene rs2271255 (Lys222Glu) and rs35996865 polymorphisms, and ROCK2 gene rs726843, rs2290156, rs10178332, and rs35768389 (Asp601Val) polymorphisms were associated with RDS. However, no associations were found with rs73963110, rs1515219, rs965665, rs2230774 (Thr431Asn), rs6755196, and rs10929732 polymorphisms. Additionally, 12 haplotypes (6 in ROCK1 and 6 in ROCK2) were found to be markedly associated with RDS. This is the first study to examine the involvement of ROCK gene variation in the risk of incident RDS. The results strongly suggest that ROCK gene polymorphisms may modify individual susceptibility to RDS in the Turkish population. Copyright © 2016. Published by Elsevier B.V.

  1. Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction.

    Science.gov (United States)

    Ohashi, Kazumasa; Fujiwara, Sachiko; Mizuno, Kensaku

    2017-03-01

    All cells sense and respond to various mechanical forces in and mechanical properties of their environment. To respond appropriately, cells must be able to sense the location, direction, strength and duration of these forces. Recent progress in mechanobiology has provided a better understanding of the mechanisms of mechanoresponses underlying many cellular and developmental processes. Various roles of mechanoresponses in development and tissue homeostasis have been elucidated, and many molecules involved in mechanotransduction have been identified. However, the whole picture of the functions and molecular mechanisms of mechanotransduction remains to be understood. Recently, novel mechanisms for sensing and transducing mechanical stresses via the cytoskeleton, cell-substrate and cell-cell adhesions and related proteins have been identified. In this review, we outline the roles of the cytoskeleton, cell-substrate and cell-cell adhesions, and related proteins in mechanosensing and mechanotransduction. We also describe the roles and regulation of Rho-family GTPases in mechanoresponses. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  2. Dependence of Core and Extended Flux on Core Dominance ...

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... Based on two extragalactic radio source samples, the core dominance parameter is calculated, and the correlations between the core/extended flux density and core dominance parameter are investigated. When the core dominance parameter is lower than unity, it is linearly correlated with the core flux ...

  3. Earth's inner core: Innermost inner core or hemispherical variations?

    NARCIS (Netherlands)

    Lythgoe, K. H.; Deuss, A.; Rudge, J. F.; Neufeld, J. A.

    2014-01-01

    The structure of Earth's deep inner core has important implications for core evolution, since it is thought to be related to the early stages of core formation. Previous studies have suggested that there exists an innermost inner core with distinct anisotropy relative to the rest of the inner core.

  4. Dependence of Core and Extended Flux on Core Dominance ...

    Indian Academy of Sciences (India)

    Abstract. Based on two extragalactic radio source samples, the core dominance parameter is calculated, and the correlations between the core/extended flux density and core dominance parameter are investi- gated. When the core dominance parameter is lower than unity, it is linearly correlated with the core flux density, ...

  5. 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.)

  6. rhoCentralRfFoam: An OpenFOAM solver for high speed chemically active flows - Simulation of planar detonations -

    Science.gov (United States)

    Gutiérrez Marcantoni, L. F.; Tamagno, J.; Elaskar, S.

    2017-10-01

    A new solver developed within the framework of OpenFOAM 2.3.0, called rhoCentralRfFoam which can be interpreted like an evolution of rhoCentralFoam, is presented. Its use, performing numerical simulations on initiation and propagation of planar detonation waves in combustible mixtures H2-Air and H2-O2-Ar, is described. Unsteady one dimensional (1D) Euler equations coupled with sources to take into account chemical activity, are numerically solved using the Kurganov, Noelle and Petrova second order scheme in a domain discretized with finite volumes. The computational code can work with any number of species and its corresponding reactions, but here it was tested with 13 chemically active species (one species inert), and 33 elementary reactions. A gaseous igniter which acts like a shock-tube driver, and powerful enough to generate a strong shock capable of triggering exothermic chemical reactions in fuel mixtures, is used to start planar detonations. The following main aspects of planar detonations are here, treated: induction time of combustible mixtures cited above and required mesh resolutions; convergence of overdriven detonations to Chapman-Jouguet states; detonation structure (ZND model); and the use of reflected shocks to determine induction times experimentally. The rhoCentralRfFoam code was verified comparing numerical results and it was validated, through analytical results and experimental data.

  7. An Adaptor Molecule Afadin Regulates Lymphangiogenesis by Modulating RhoA Activity in the Developing Mouse Embryo.

    Directory of Open Access Journals (Sweden)

    Takashi Majima

    Full Text Available Afadin is an intracellular binding partner of nectins, cell-cell adhesion molecules, and plays important roles in the formation of cell-cell junctions. Afadin-knockout mice show early embryonic lethality, therefore little is known about the function of afadin during organ development. In this study, we generated mice lacking afadin expression in endothelial cells, and found that the majority of these mice were embryonically lethal as a result of severe subcutaneous edema. Defects in the lymphatic vessels of the skin were observed, although the morphology in the blood vessels was almost normal. Severe disruption of VE-cadherin-mediated cell-cell junctions occurred only in lymphatic endothelial cells, but not in blood endothelial cells. Knockout of afadin did not affect the differentiation and proliferation of lymphatic endothelial cells. Using in vitro assays with blood and lymphatic microvascular endothelial cells (BMVECs and LMVECs, respectively, knockdown of afadin caused elongated cell shapes and disruption of cell-cell junctions among LMVECs, but not BMVECs. In afadin-knockdown LMVECs, enhanced F-actin bundles at the cell periphery and reduced VE-cadherin immunostaining were found, and activation of RhoA was strongly increased compared with that in afadin-knockdown BMVECs. Conversely, inhibition of RhoA activation in afadin-knockdown LMVECs restored the cell morphology. These results indicate that afadin has different effects on blood and lymphatic endothelial cells by controlling the levels of RhoA activation, which may critically regulate the lymphangiogenesis of mouse embryos.

  8. 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

    kinase inhibitor Y-27632 and the phosphatidyl-inositol 3 kinase (PI3K) inhibitor wortmannin. The maximal rates of swelling-activated K+ (86 Rb+ as tracer) and taurine ([3H]taurine as tracer) efflux after a 30 % reduction in extracellular osmolarity were increased about twofold in cells with maximal Rho......AV14 expression compared to wild-type cells, but were unaffected by Y-27632. The volume set points for activation of release of both osmolytes appeared to be reduced by RhoAV14 expression. The maximal taurine efflux rate constant was potentiated by the tyrosine phosphatase inhibitor Na(3)VO(4......), and inhibited by the tyrosine kinase inhibitor genistein. The magnitude of the swelling-activated Cl- current (I(Cl,swell) ) was higher in RhoAV14 than in wild-type cells after a 7.5 % reduction in extracellular osmolarity, but, in contrast to 86Rb+ and [3H]taurine efflux, similar in both strains after a 30...

  9. SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction.

    Science.gov (United States)

    Pasquier, Jennifer; Abu-Kaoud, Nadine; Abdesselem, Houari; Madani, Aisha; Hoarau-Véchot, Jessica; Thawadi, Hamda Al; Vidal, Fabien; Couderc, Bettina; Favre, Gilles; Rafii, Arash

    2015-08-01

    The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites. Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases. We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion. We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases.

  10. SDF-1alpha concentration dependent modulation of RhoA and Rac1 modifies breast cancer and stromal cells interaction

    International Nuclear Information System (INIS)

    Pasquier, Jennifer; Abu-Kaoud, Nadine; Abdesselem, Houari; Madani, Aisha; Hoarau-Véchot, Jessica; Thawadi, Hamda Al.; Vidal, Fabien; Couderc, Bettina; Favre, Gilles; Rafii, Arash

    2015-01-01

    The interaction of SDF-1alpha with its receptor CXCR4 plays a role in the occurrence of distant metastasis in many solid tumors. This interaction increases migration from primary sites as well as homing at distant sites. Here we investigated how SDF-1α could modulate both migration and adhesion of cancer cells through the modulation of RhoGTPases. We show that different concentrations of SDF-1α modulate the balance of adhesion and migration in cancer cells. Increased migration was obtained at 50 and 100 ng/ml of SDF-1α; however migration was reduced at 200 ng/ml. The adhesion between breast cancer cells and BMHC was significantly increased by SDF-1α treatment at 200 ng/ml and reduced using a blocking monoclonal antibody against CXCR4. We showed that at low SDF-1α concentration, RhoA was activated and overexpressed, while at high concentration Rac1 was promoting SDF-1α mediating-cell adhesion. We conclude that SDF-1α concentration modulates migration and adhesion of breast cancer cells, by controlling expression and activation of RhoGTPases. The online version of this article (doi:10.1186/s12885-015-1556-7) contains supplementary material, which is available to authorized users

  11. 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; Karentzos, Efstathios; Karpov, Sergey; Karpova, Zoya; Karthik, Krishnaiyengar; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kasahara, Kota; Kashif, Lashkar; Kass, Richard; Kastanas, Alex; Kataoka, Yousuke; Kato, Chikuma; Katre, Akshay; Katzy, Judith; Kawade, Kentaro; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kay, Ellis; Kazanin, Vassili; Keeler, Richard; Kehoe, Robert; Keller, John; Kellermann, Edgar; Kempster, Jacob Julian; Kendrick, James; Keoshkerian, Houry; Kepka, Oldrich; Kerševan, Borut Paul; Kersten, Susanne; Keyes, Robert; Khader, Mazin; Khalil-zada, Farkhad; Khanov, Alexander; Kharlamov, Alexey; Kharlamova, Tatyana; Khodinov, Alexander; Khoo, Teng Jian; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kido, Shogo; Kilby, Callum; Kim, Hee Yeun; Kim, Shinhong; Kim, Young-Kee; Kimura, Naoki; Kind, Oliver Maria; King, Barry; Kirchmeier, David; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kitali, Vincent; Kivernyk, Oleh; Kladiva, Eduard; Klapdor-Kleingrothaus, Thorwald; 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; Madaffari, Daniele; Madar, Romain; Mader, Wolfgang; Madsen, Alexander; Madysa, Nico; Maeda, Junpei; Maeland, Steffen; Maeno, Tadashi; Maevskiy, Artem; Magerl, Veronika; Maiani, Camilla; Maidantchik, Carmen; Maier, Thomas; Maio, Amélia; Majersky, Oliver; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Malaescu, Bogdan; Malecki, Pawel; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Claire; Maltezos, Stavros; Malyukov, Sergei; Mamuzic, Judita; Mancini, Giada; Mandić, Igor; Maneira, José; Manhaes de Andrade Filho, Luciano; Manjarres Ramos, Joany; Mankinen, Katja Hannele; Mann, Alexander; Manousos, Athanasios; Mansoulie, Bruno; Mansour, Jason Dhia; Mantifel, Rodger; Mantoani, Matteo; Manzoni, Stefano; Mapelli, Livio; Marceca, Gino; March, Luis; Marchese, Luigi; Marchiori, Giovanni; Marcisovsky, Michal; Marin Tobon, Cesar Augusto; Marjanovic, Marija; Marley, Daniel; Marroquim, Fernando; Marsden, Stephen Philip; Marshall, Zach; Martensson, Mikael; Marti-Garcia, Salvador; 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; Pacheco Pages, Andres; Pacheco Rodriguez, Laura; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganini, Michela; Paige, Frank; Palacino, Gabriel; Palazzo, Serena; Palestini, Sandro; Palka, Marek; Pallin, Dominique; Panagiotopoulou, Evgenia; Panagoulias, Ilias; Pandini, Carlo Enrico; Panduro Vazquez, William; Pani, Priscilla; Panitkin, Sergey; Pantea, Dan; Paolozzi, Lorenzo; Papadopoulou, Theodora; Papageorgiou, Konstantinos; Paramonov, Alexander; Paredes Hernandez, Daniela; Parker, Adam Jackson; Parker, Michael Andrew; Parker, Kerry Ann; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pascuzzi, Vincent; Pasner, Jacob Martin; Pasqualucci, Enrico; Passaggio, Stefano; Pastore, Francesca; Pataraia, Sophio; Pater, Joleen; Pauly, Thilo; Pearson, Benjamin; Pedraza Lopez, Sebastian; Pedro, Rute; Peleganchuk, Sergey; Penc, Ondrej; Peng, Cong; Peng, Haiping; Penwell, John; Peralva, Bernardo; Perego, Marta Maria; Perepelitsa, Dennis; Peri, Francesco; Perini, Laura; Pernegger, Heinz; Perrella, Sabrina; 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; 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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; 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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; 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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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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 ac