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Sample records for active rs cvn

  1. RS CVn stars - Chromospheric phenomena

    NASA Technical Reports Server (NTRS)

    Bopp, B. W.

    1983-01-01

    The observational information regarding chromospheric emission features in surface-active RS CVn stars is reviewed. Three optical features are considered in detail: Ca II H and K, Balmer H-alpha and He I 10830 A. While the qualitative behavior of these lines is in accord with solar-analogy/rotation-activity ideas, the quantitative variation and scaling are very poorly understood. In many cases, the spectroscopic observations with sufficient SNR and resolution to decide these questions have simply not yet been made. The FK Com stars, in particular, present extreme examples of rotation that may well tax present understanding of surface activity to its limits.

  2. Long-Term Starspot Activity of Some Chromospherically Active Rs CVn and BY Dra Stars

    NASA Astrophysics Data System (ADS)

    Kozhevnikova, Alla; Ilya, Alekseev

    2016-10-01

    We present results of our long-term photometric observations of a sample of 15 chromospherically active BY Dra and RS CVn-type stars. Observations were carried out at a 70-cm telescope and multichannel photometer of Kourovka Astronomical Observatory of Ural Federal University and at a 1.25-m telescope of Crimean Astrophysical Observatory from 2003 to 2015 in Johnson B, V, R, I bands. We also use the previously published photometric data for all these stars to find the meaning of historical star's brightness, that we assume as a brightness of unspotted photosphere. Using a renewed zonal spot model for spotted stellar photospheres we determined spot parameters for all observational seasons, as our as published ones, that were spanning almost over 45 years for some stars (e.g. CG Cyg, WY Cnc, EV Lac, V 1396 Cyg). It is shown that the spots were located at low and middle latitudes up to 58 deg., are cooler than the surrounding photosphere by 200 - 2000 K according to the spectral class. The spotted area varied from season to season, comprising 13%-47% of the surface area of the star. Almost half of the stars display drifts of their spots towards the equator and poles during certain time intervals; however, the speeds of the spots' latitude drifts are lower than the analogous speeds for sunspots, by factors of 1.5-4, on average. Activity cycles lasting from 5 to 40 years have been determined or confirmed for majority of the studied stars. As a rule, cycles are expressed in synchronous variations of spot areas, spot latitudes and average photometric star's brightness.

  3. Models for the active and quiescent regions on the RS CVN-type system 2 Pegasi (HD 224085)

    NASA Technical Reports Server (NTRS)

    Linsky, J. L.; Brown, A.; Marstad, N. C.; Rodono, M.; Andrews, A. D.; Butler, C. J.; Byrne, P. B.

    1984-01-01

    The IUE observations of the RS CVn binary system II Pegasi obtained during the period 1981 October 1-7 were used to derive the emission measure distributions and to calculate transmission region models of the quiescent and plage (active) regions of II Peg. Active region models were calculated assuming area coverages of 10%, 6%, 3% and 1% of the visible hemisphere. These models are used to provide lower limits to the electron pressure in the quiescent and plage regions, which are compared with the available density diagnostics. The amount of mechanical energy deposition required to account for the observed radiative losses is very large.

  4. Radio emission from RS CVn binary systems

    SciTech Connect

    Doiron, D.J.

    1984-01-01

    The RS CVn binary stellar systems UX Ari, HR 1099, AR Lac, HR 5110, II Peg, lambda And, and SZ Psc were investigated by use of radio interferometry during the period from July 1982 through August 1983. Interferometry took two forms: Very Large Array (VLA) observations and Very Long Baseline Interferometry (VLBI). The VLA observations determined the characteristic polarization and flux behavior of the centimeter wavelength radio emission. The observed spectral index was near zero during quiescent periods, rising to between 0.5 and 1.0 during active periods. No net linear polarization is observed to a limit of 1.7%. This is expected since the Faraday depth of thermal electrons deduced from x-ray observations is approx. 10/sup 5/. Circular polarization is observed to be less than 20% at all frequencies often with a helicity reversal between 1.6 GHz and 5 GHz. The VLBI observations have shown that the brightness temperatures are often T/sub B/ approx.> 10/sup 10/ /sup 0/K and size sources smaller than or comparable to the overall size of the binary system. These data are consistent with incoherent gyrosynchrotron emission from mildly relativistic electrons which are optically thick to their own radiation at 1.6 GHz and optically thin at 5 GHz and above. The spectral behavior suggests that the radio emission is due to a power-law distribution of electrons.

  5. A Three Dimensional Picture of RS CVN Stellar Atmospheres

    NASA Astrophysics Data System (ADS)

    Linsky, Jeffrey L.

    The ROSAT all-sky survey provides a unique opportunity to study an RS CVn system simultaneously at x-ray, EUV, UV, optical, and radio wavelengths at many phases throughout an orbital period. ROSAT can detect the x-ray flux of each candidate system during each 30 second viewing 16 times per day for at least 2 days. We request a block of 7 IUE shifts to obtain NEAR SIMULTANEOUS emission line fluxes (SWP-LO) and Mg IT line profiles (LWP-HI), and we will obtain contemporaneous optical photometry and spectroscopy and VLA radio fluxes (3.6, 6, and 20 cm). one objective of this PROPOSAL is to obtain the FIRST 3-D MODEL OF THE INHOMOGENEOUS PHOTOSPHERE, CHROMOSPHERE, AND CORONA OF A STAR OTHER THAN THE SUN. We will use optical photometry and spectroscopy to map the spotted photospheres of each star, and the Mg II line profiles to DOPPLERIMAGE their chromospheres, to determine the location, size, and surface flux of the active regions. We will then use the time variation of the UV emission line and x-ray fluxes to determine what fluxes are due to the quiet and active regions separately. These data will provide SURFACE FLUXES for the quiet and active regions separately. We will then will model BOTH REGIONS independently using an emission measure analysis. We will also model any flares observed. The second part of the program will be a simultaneous UV/X-ray SURVEY with the objective of DETERMINING THE RANGE OF PHYSICAL MODELS APPLICABLE TO THE CHROMOSPHERES AND CORONAE OF RS CVN SYSTEMS. We propose to obtain emission line fluxes (SWP-LO) and Mg II line profiles (LWP-HI) of all bright RS CVns observed by ROSAT from mid-July through September 1990 that meet the IUE observing constraints. About 17 systems in the Strassmeier catalog will likely be observed during this period. While many RS CVn systems have been observed separately by IUE and x-ray satellites, SIMULTANEOUS UV and x-ray observations are required to model these spatially inhomogenous and timevariable systems. This

  6. Radio polarization characteristics of two RS CVn binaries

    NASA Technical Reports Server (NTRS)

    Mutel, R. L.; Lestrade, J.-F.; Doiron, D. J.

    1985-01-01

    The results of multifrequency epoch VLA observations of polarized radio emission from the nearby active RS CVn binaries UX Arietis and HR 1099 are reported. For both systems, there is an excellent correlation between handedness of circular polarization and frequency. Helicity reversal is almost always seen between 1.4 and 5.0 GHz, possibly due to optical depth effects. There may also be an anticorrelation between total intensity and fractional circular polarization, especially at 5 GHz. This is consistent with models in which intense flares are associated with compact selfabsorbed synchrotron sources, while the quiescent emission arises from larger gyrosynchrotron-emitting plasma.

  7. RS CVn binaries: Testing the solar-stellar dynamo connection

    NASA Technical Reports Server (NTRS)

    Dempsey, R.

    1995-01-01

    We have used the Extreme Ultraviolet Explorer satellite to study the coronal emission from the EUV-bright RS CVn binaries Sigma2 CrB, observed February 10-21, 1994, and II Peg, observed October 1-5, 1993. We present time-resolved and integrated EUV short-, medium-, and long-wavelength spectra for these binaries. Sigma2 CrB shows significant first-order emission features in the long-wavelength region. The coronal emission distributions and electron densities are estimated for those active coronae dominated by high temperature plasma.

  8. The Eclipsing Binary Pulsar PSR B1718-19: a Clean RS CVN System?

    NASA Astrophysics Data System (ADS)

    Kaspi, Victoria

    1996-07-01

    We request WFPC2 observations of the eclipsing binary pulsarPSR B1718-19. This slowly-rotating pulsar lies in thedirection of the globular cluster NGC 6342, and defiesstandard binary pulsar formation models in which the pulsar is``spun-up'' via mass accretion. Furthermore, the observedeclipses cannot be explained with standard models. Thispulsar's unusual properties can be explained elegantly if itscompanion is an active, non-degenerate star like thoseobserved in RS CVn systems, but in this case, subject only togravity. Following Keck observations of the field, we proposeHST observations of PSR B1718-19 to detect and studyvariability in the companion, in order to answer the followingquestions. 1- Are the eclipses seen in PSR B1718-19 indeed aresult of RS CVn-type activity in the companion, and what isthe evolutionary history of the binary? 2- Is the activity inRS CVn systems purely a tidal effect? 3- How are mass loss,rotation, and surface activity related in RS CVn stars? 4- IsPSR B1718-19 in NGC 6342?

  9. The photospheric abundances of active binaries. II. Atmospheric parameters and abundance patterns for 6 single-lined RS CVn systems

    NASA Astrophysics Data System (ADS)

    Morel, T.; Micela, G.; Favata, F.; Katz, D.; Pillitteri, I.

    2003-12-01

    Photospheric parameters and abundances are presented for a sample of single-lined chromospherically active binaries from a differential LTE analysis of high-resolution spectra. Abundances have been derived for 13 chemical species, including several key elements such as Li, Mg, and Ca. Two methods have been used. The effective temperatures, surface gravities and microturbulent velocities were first derived from a fully self-consistent analysis of the spectra, whereby the temperature is determined from the excitation equilibrium of the Fe I lines. The second approach relies on temperatures derived from the (B-V) colour index. These two methods give broadly consistent results for the stars in our sample, suggesting that the neutral iron lines are formed under conditions close to LTE. We discuss the reliability in the context of chromospherically active stars of various colour indices used as temperature indicators, and conclude that the (V-R) and (V-I) colours are likely to be significantly affected by activity processes. Irrespective of the method used, our results indicate that the X-ray active binaries studied are not as metal poor as previously claimed, but are at most mildly iron-depleted relative to the Sun (-0.41protect <~ [Fe/H]protect la +0.11). A significant overabundance of several chemical species is observed (e.g., the alpha -synthezised elements). These abundance patterns are discussed in relation to stellar activity. Based on observations collected at ESO (La Silla, Chile). Table A.1 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/412/495

  10. Chromospherically active stars. III - HD 26337 = EI Eri: An RS CVn candidate for the Doppler-imaging technique

    NASA Technical Reports Server (NTRS)

    Fekel, Francis C.; Quigley, Robert; Gillies, Kim; Africano, John L.

    1987-01-01

    Spectroscopic observations of the chromospherically active G5 IV single-lined binary HD 26337 = EI Eri are presented. An orbital period of 1.94722 days is found for the star. It has moderately strong Ca II H and K emission and strong ultraviolet emission features, while H-alpha is a weak absorption feature that is variable in strength. The inclination of the system is 46 + or - 12 deg, and the unseen secondary is probably a late K or early M dwarf. The v sin i of the primary is 50 + or - 3 km/s, resulting in a minimum radius of 1.9 + or - 0.1 solar radius. The star is within the required limits for Doppler imaging. The primary is close to filling its Roche lobe, resulting in a strong constraint that the mass ratio is 2.6 or greater, with a primary mass of at least 1.4 solar mass. The distance to the system is estimated at 75 pc.

  11. V474 Car: A RARE HALO RS CVn BINARY IN RETROGRADE GALACTIC ORBIT

    SciTech Connect

    Bubar, Eric J.; Mamajek, Eric E.; Jensen, Eric L. N.; Walter, Frederick M.

    2011-04-15

    We report the discovery that the star V474 Car is an extremely active, high velocity halo RS CVn system. The star was originally identified as a possible pre-main-sequence star in Carina, given its enhanced stellar activity, rapid rotation (10.3 days), enhanced Li, and absolute magnitude which places it above the main sequence (MS). However, its extreme radial velocity (264 km s{sup -1}) suggested that this system was unlike any previously known pre-MS system. Our detailed spectroscopic analysis of echelle spectra taken with the CTIO 4 m finds that V474 Car is both a spectroscopic binary with an orbital period similar to the photometric rotation period and metal-poor ([Fe/H] {approx_equal}-0.99). The star's Galactic orbit is extremely eccentric (e {approx_equal} 0.93) with a perigalacticon of only {approx}0.3 kpc of the Galactic center-and the eccentricity and smallness of its perigalacticon are surpassed by only {approx}0.05% of local F/G-type field stars. The observed characteristics are consistent with V474 Car being a high-velocity, metal-poor, tidally locked, chromospherically active binary, i.e., a halo RS CVn binary, and one of only a few such specimens known.

  12. IUE spectra of a flare in HR 5110: A flaring RS CVn or Algol system?

    NASA Technical Reports Server (NTRS)

    Simon, T.; Linsky, J. L.; Schiffer, F. H., III

    1981-01-01

    Ultraviolet spectra of the RS CVn type binary system HR 5110 were obtained with IUE on May 31, 1979 during a period of intense radio flaring of this star. High temperature transition region lines are present, but are not enhanced above observed quiescent strengths. The similarities of HR 5110 to the Algol system, As Eri, suggest that the 1979 May to June flare may involve mass exchange rather than annihilation of coronal magnetic fields.

  13. KOI-1003: A New Spotted, Eclipsing RS CVn Binary in the Kepler Field

    NASA Astrophysics Data System (ADS)

    Roettenbacher, Rachael M.; Kane, Stephen R.; Monnier, John D.; Harmon, Robert O.

    2016-12-01

    Using the high-precision photometry from the Kepler space telescope, thousands of stars with stellar and planetary companions have been observed. The characterization of stars with companions is not always straightforward and can be contaminated by systematic and stellar influences on the light curves. Here, through a detailed analysis of starspots and eclipses, we identify KOI-1003 as a new, active RS CVn star—the first identified with data from Kepler. The Kepler light curve of this close binary system exhibits the system’s primary transit, secondary eclipse, and starspot evolution of two persistent active longitudes. The near equality of the system’s orbital and rotation periods indicates the orbit and primary star’s rotation are nearly synchronized ({P}{orb}=8.360613+/- 0.000003 {days}; {P}{rot}˜ 8.23 {days}). By assuming the secondary star is on the main sequence, we suggest the system consists of a {1.45}-0.19+0.11 {M}⊙ subgiant primary and a {0.59}-0.04+0.03 {M}⊙ main-sequence companion. Our work gives a distance of 4400 ± 600 pc and an age of t={3.0}+2.0-0.5 {Gyr}, parameters which are discrepant with previous studies that included the star as a member of the open cluster NGC 6791.

  14. Southern RS CVn systems - Candidate list. [spectral catalog of variable binary stars

    NASA Technical Reports Server (NTRS)

    Weiler, E. J.; Stencel, R. E.

    1979-01-01

    A list of 43 candidate RS CVn binary systems in the far southern hemisphere of the sky (south of -40 deg declination) is presented. The candidate systems were selected from the first two volumes of the Michigan Spectral Catalog (1975, 1978), which provides MK classifications for southern HD stars and identifies any unusual characteristics noted for individual stellar spectra. The selection criteria used were: (1) the occurrence of Ca II H and K emission; (2) known or suspected binary nature; (3) regular light variations of zero to one magnitude; and (4) spectral type between F0 and K2 and luminosity less than bright giant (II).

  15. Detection of an X-ray flare in the RS CVn binary Sigma Coronae Borealis

    NASA Technical Reports Server (NTRS)

    Agrawal, P. C.; Rao, A. R.; Riegler, G. R.

    1986-01-01

    The detection of an X-ray flare in the RS CVn binary Sigma Coronae Borealis with the Monitor Proportional Counter on the Einstein Observatory is described. During the 513 min of observation, an X-ray flare of 208 min duration was detected at a significance level of 26 sigma in the 1.19-10.16 keV band. The rise time of the flare is between 25 and 70 min and the decay time is greater than or equal to 34 min. The X-ray luminosity at the flare maximum is found to be 6 x 10 to the 30th erg/s and the total energy radiated in X-rays during the flare is 2 x 10 to the 34th erg. The energy spectrum in the flaring state is found to be harder (temperature T about 2.5 x 10 to the 7th K) compared to the one observed in the quiescent state (T about 6 x 10 to the 6th K). Applying the coronal loop model, the loop parameters are calculated and compared for the X-ray flares observed in the various RS CVn binaries and the sun. The significance of the differences in the observed and derived parameters of the X-ray flares is briefly discussed.

  16. Radio emission from RS CVn binaries. II. Polarization and spectral properties

    SciTech Connect

    Mutel, R.L.; Morris, D.H.; Doiron, D.J.; Lestrade, J.F.

    1987-05-01

    Multiepoch radio observations of circular polarization and spectral characteristics of several close, late-type stellar binaries are reported. The median luminosity of four well-studied systems ranged from 16.2 to 17.1 ergs/s/Hz. For individual systems, the fractional circular polarization decreases with increasing luminosity, particularly at frequencies above 5 GHz. Eclipsing binaries have significantly lower average circular polarization compared with noneclipsing systems. Helicity reversal is almost always observed between 1.4 and 4.9 GHz for systems with high orbital inclination. Comparison with ten years of previously published polarization observations for two RS CVn stellar systems show that the same helicity occurs at a given frequency for a given source, indicating a very stable, large-scale magnetic field geometry. These spectral and polarization characteristics strongly support a model of inhomogeneous gyrosynchrotron emission arising from electrons with power law energy spectra interacting with inhomogeneous magnetic fields. 35 references.

  17. Radio emission from RS CVn binaries. II - Polarization and spectral properties

    NASA Technical Reports Server (NTRS)

    Mutel, R. L.; Morris, D. H.; Doiron, D. J.; Lestrade, J. F.

    1987-01-01

    Multiepoch radio observations of circular polarization and spectral characteristics of several close, late-type stellar binaries are reported. The median luminosity of four well-studied systems ranged from 16.2 to 17.1 ergs/s/Hz. For individual systems, the fractional circular polarization decreases with increasing luminosity, particularly at frequencies above 5 GHz. Eclipsing binaries have significantly lower average circular polarization compared with noneclipsing systems. Helicity reversal is almost always observed between 1.4 and 4.9 GHz for systems with high orbital inclination. Comparison with ten years of previously published polarization observations for two RS CVn stellar systems show that the same helicity occurs at a given frequency for a given source, indicating a very stable, large-scale magnetic field geometry. These spectral and polarization characteristics strongly support a model of inhomogeneous gyrosynchrotron emission arising from electrons with power law energy spectra interacting with inhomogeneous magnetic fields.

  18. Comment on the three-body theory for period changes in RS CVn systems

    NASA Technical Reports Server (NTRS)

    Van Buren, D.

    1986-01-01

    In the three-body theory for period variations in RS CVn systems, the timing residuals are interpreted as light-travel time differences as the eclipsing system moves about the barycenter of the triple. These residuals can require a larger orbit than Kepler's law allows, given the time scale of the period variations. For only two of eight systems investigated, SV Cam and V471 Tau, is the theory plausible in that the inferred barycentric motion of the binary is smaller than the orbit of the third body, and the inferred properties of the third body are both reasonable and consistent with its remaining hidden. The theory is thus not a general theory for period changes. Observational testing of the theory is straightforward and may lead to the detection of 'brown dwarfs' associated with eclipsing systems through their kinematic effects.

  19. The RS CVn Binary HD 155555: A Comparative Study of the Atmospheres for the Two Component Stars

    NASA Technical Reports Server (NTRS)

    Airapetian, V. S.; Dempsey, R. C.

    1997-01-01

    We present GHRS/HST observations of the RS CVn binary system HD 155555. Several key UV emission lines (Fe XXI, Si IV, O V, C IV) have been analyzed to provide information about the heating rate throughout the atmosphere from the chromosphere to the corona. We show that both the G and K components reveal features of a chromosphere, transition region and corona. The emission measure distribution as a function of temperature for both components is derived and compared with the RS Cvn system, HR 1099, and the Sun. The transition region and coronal lines of both stars show nonthermal broadenings of approx. 20-30 km/s. Possible physical implications for coronal heating mechanisms are discussed.

  20. Rotational modulation and flares on RS Canum Venaticorum and BY Draconis stars. 18: Coordinated VLA, ROSAT, and IUE observations of RS CVn binaries

    NASA Technical Reports Server (NTRS)

    Fox, David C.; Linsky, Jeffrey L.; Veale, Anthony; Dempsey, Robert C.; Brown, Alex; Neff, James E.; Pagano, Isabella; Rodono, Marcello; Bromage, Gordon E.; Kuerster, Martin

    1994-01-01

    As part of a coordinated program of multi-wavelength observations of RS CVn close binary systems, we observed 15 systems with the Very Large Array (VLA) and 10 systems with IUE, simultaneously or nearly simultaneously with the ROSAT All Sky Survey observations of these stars. Of the 22 systems observed with ROSAT, three were observed both by IUE and the VLA. Radio observations were made at 3.6, 6 and 20 cm. Of the 15 observed RS CVn systems, we detected 11 with greater than 4 sigma confidence at one or more wavelengths. The IUE observations were made within the RIASS (ROSAT-IUE All Sky Survey) program. We present the results of the VLA observations, along with the corresponding subsets of the ROSAT Position Sensitive Proportional Counter (PSPC) X-ray and Wide Field Camera (WFC) XUV survey, and RIASS IUE observations. We obtained an extended VLA/IUE/ROSAT simultaneous coverage of one system, TY Pyx, covering more than one orbital period. These observations reveal that the quiescent radio flux of TY Pyx is relatively constant over time scales of up to 7 hours, but that it did change by a factor of 3 over 24 hours, probably due to a flare on 1990 Nov. 12. The UV, XUV and X-ray fluxes do not show large day-to-day or phase-related variability. The observation of the decay phase of a radio flare on EI Eri, with no accompanying X-ray or XUV flare, suggests that the lack of a strong correlation between X-ray and radio flares previously noted for dMe flare stars holds for RS CVn systems as well. We suggest that the radio flare may have been due to a coherent emission process such as electron cyclotron emission. The simultaneous measurements presented here provide a unique test of the general correlation between radio and soft X-ray luminosities, L(sub radio) approximately L(sub x exp m) (Drake et al. 1989) with a power-law slope close to unity, which was previously derived using data obtained years apart. Our derived slopes are consistent with and thus support the general

  1. Long-term Optical Activity of the Hard X-ray Flaring Star DG CVn

    NASA Astrophysics Data System (ADS)

    Šimon, V.

    2017-04-01

    DG CVn is a young late-type star which displayed an X-ray and optical superflare in 2014. This paper presents an analysis of the long-term activity of this object in the optical band. I used the photographic data from DASCH (Digital Access to a Sky Century @ Harvard). These measurements from the years 1895-1989 cover the blue spectral region. CCD V-band ASAS data were used for several UV Cet-type stars to place the activity of DG CVn in the context of flaring stars. I show that three large brightenings (flares) of DG CVn by more than 1 mag were detected on the DASCH plates. The character of the long-term activity (regarding the histogram of brightness) of DG CVn is compatible with those of flaring stars UV Cet and V371 Ori. The flares brighter than ˜ 0.4 mag represent less than 1 percent of the observed data in all three objects

  2. BD Andromedae: A new short-period RS CVn eclipsing binary star with a distant tertiary body in a highly eccentric orbit

    SciTech Connect

    Kim, Chun-Hwey; Song, Mi-Hwa; Yoon, Jo-Na; Jeong, Min-Ji; Han, Wonyong

    2014-06-20

    A photometric study of BD And was made through the analysis of two sets of new BVR light curves. The light curves with migrating photometric waves outside eclipse show that BD And is a short-period RS CVn-type binary star. The analysis of all available timings reveals that the orbital period has varied in a strictly cyclical way with a period of 9.2 yr. The periodic variation most likely arises from the light-time effect due to a tertiary moving in a highly elliptical orbit (e {sub 3} = 0.76). The Applegate mechanism could not operate properly in the eclipsing pair. The light curves were modeled with two large spots on the hotter star and a large third light amounting to about 14% of the total systemic light. BD And is a triple system: a detached binary system consisting of two nearly equal solar-type stars with an active primary star and a G6-G7 tertiary dwarf. The absolute dimensions of the eclipsing pair and tertiary components were determined. The three components with a mean age of about 5.8 Gyr are located at midpositions in main-sequence bands. The radius of the secondary is about 17% larger than that deduced from stellar models. The orbital and radiometric characteristics of the tertiary are intensively investigated. One important feature is that the mutual inclination between two orbits is larger than 60°, implying that Kozai cycles had occurred very efficiently in the past. The possible past and future evolutions of the BD And system, driven by KCTF and MBTF, are also discussed.

  3. Theoretical studies of the RS Canum Venaticorum stars

    NASA Technical Reports Server (NTRS)

    Mullan, D. J.

    1982-01-01

    The activity in RS Canum Venaticorum (CVn) is investigated. Models for chromospheric structure are developed and the role of magnetic fields both in the photosphere as well as in the chromosphere and upper atmosphere are examined. T Tau stars are also studied from the same points of view. The properties of magnetic field loops are used to help understand the atmospheric structure in RS CVn stars. The concepts developed in the case of these stars appear to be applicable over a much broader region of the HR diagram. The absence of stable magnetic loops in the atmospheres of late type giant stars suggests that the atmospheres of RS CVn active components are qualitatively distinct from the solar atmosphere.

  4. Rotational-modulation mapping of the active atmosphere of the RS Canum Venaticorum binary HD 106225

    NASA Astrophysics Data System (ADS)

    Strassmeier, K. G.

    1994-01-01

    Observations of rotational modulation of photospheric absorption lines, chromospheric emission lines, and the continuum brightness of the RS CVn binary HD 106225 Pord = 10.4 days) are reported. From Doppler imaging of four photosperic lines we obtain the surface temperatures distribution at two observing epochs in 1991. Spot temperatures on HD 106225 were determined from three different proxy indicators (photometric broad-band colors, line-depth ratios, and line-profile shapes) and yield values between 1000-1500 K. Simultaneous Ca II H and K and H-alpha line-profile variations provide some clues on the spatial relation between the temperature distribution of the photosphere and the location of active regions in the chromosphere and we present, for the first time, a crude three-dimensional picture of a stellar atmosphere. Simultaneous and contemporaneous UBV photometry is used to trace the evolution of spotted regions in 1991. We applied a time-series spot modeling code and found a fairly stable spot configuration with two major spots. Only small and sporadic spot-area changes were present in 1991, which likely are unrelated to a long-term cycle.

  5. On the Light Curves of AM CVn

    NASA Astrophysics Data System (ADS)

    Smak, J.

    2017-03-01

    Light curves of AM CVn are analyzed by decomposing them into their Fourier components. The amplitudes of the fundamental mode and overtones of the three components: the superhumps, the negative superhumps and the orbital variations, are found to be variable. This implies that variations in the shape of the observed light curve of AM CVn are not only due to the interference between those components, but also due to the intrinsic variability within these components.

  6. Rotational modulation and flares on RS CVn and BY Dra-type stars. I - Photometry and spot models for BY Dra, AU Mic, AR Lac, II Peg and V 711 Tau (= HR 1099)

    NASA Technical Reports Server (NTRS)

    Rodono, M.; Cutispoto, G.; Pazzani, V.; Catalano, S.; Byrne, P. B.

    1986-01-01

    Multicolor wide-band photometry of five active stars is presented. The observations were carried out at several places before, during and after the period of IUE observations for the purpose of determining the location, sizes, and evolution of photospheric spots at the time when chromospheric, transition region, and coronal activity data were obtained from UV and radio observations. II Peg, BY Dra, and AU Mic show fairly stable quasi-sinusoidal light curves, while AR Lac and V 711 Tau show double-peaked light curves. For V 711 Tau, a remarkable evolution of the spotted area extent and/or longitude distribution is found. Small, but definite color variations that are consistent with the cool spot hypothesis have also been detected for BY Dra, II Peg and V 711 Tau.

  7. Radio outbursts in RS Canum Venaticorum stars - coronal heating and electron runaway

    SciTech Connect

    Mullan, D.J.

    1985-08-01

    Radio outbursts of RS CVn stars are sometimes thought of as analogs of flares in red dwarf stars. The possibility is examined that the outbursts are not due to flares, but rather to a highly efficient case of coronal heating: mechanical energy reaching the corona from the convection zone of an RS CVn star gives rise to induced electric fields which may be so large that electron runaway becomes possible. It is proposed that gyrosynchrotron emission from fast electrons which are produced by this process are the source of radio outbursts from RS CVn stars. 31 references.

  8. CVN 78 Gerald R. Ford Class Nuclear Aircraft Carrier (CVN 78)

    DTIC Science & Technology

    2015-12-01

    Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-223 CVN 78 Gerald R. Ford Class Nuclear Aircraft Carrier (CVN 78) As of FY 2017 President’s...POE - Program Office Estimate RDT&E - Research, Development, Test, and Evaluation SAR - Selected Acquisition Report SCP - Service Cost Position TBD...Preparation contract was awarded the same day. This modification included the remaining component and steel fabrication and selected construction unit

  9. CVN 78 Gerald R. Ford Class Nuclear Aircraft Carrier (CVN 78)

    DTIC Science & Technology

    2013-12-01

    E IOT &E Start ..:<! IOT &E Complete -· Platform-Level Integration .. ...:<! CVN 78 Milestones SAR Baseline Dev Est Current APB Development...Information Retrieval Dev Est - Development Estimate DoD - Department of Defense DSN - Defense Switched Network Econ - Economic Eng - Engineering Est...Capabil... -Follow-on Ship (CVN 79) DAB Program Review - • Start Construction - • Delivery .-:K IOT &E IOT &E Start .-:41 IOT &E Complete e(41 Follow-on

  10. Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

    DTIC Science & Technology

    2016-03-08

    Service, May 29, 2011, accessed online on June 1, 2011 at http://www.navy.mil/search/display.asp?story_id=60686. See also Peter Frost, “U.S. Navy’s Next...activities where they can most efficiently be performed. The CVN 79 build sequence installs 20 percent more parts in shop , and 30 percent more parts on...being accomplished late in the build cycle. So we are rewriting the build plan for CVN-79, do more work in the shops where it’s more efficient, more

  11. New Ultraviolet Observations of AM CVn

    NASA Astrophysics Data System (ADS)

    Wade, Richard A.; Eracleous, Michael; Flohic, Hélène M. L. G.

    2007-11-01

    We have obtained observations of the ultraviolet spectrum of AM CVn, an ultrashort-period helium cataclysmic variable, using the Space Telescope Imaging Spectrograph aboard the Hubble Space Telescope (HST). We obtained data in time-tag mode during two consecutive orbits of HST, covering 1600-3150 and 1140-1710 Å, respectively. The mean spectrum is approximately flat in fν. The absorption profiles of the strong lines of N V, Si IV, C IV, He II, and N IV are blueshifted and in some cases asymmetric, evidencing a wind that is partly occulted by the accretion disk. There is weak redshifted emission from N V and He II. The profiles of these lines vary mildly with time. The light curve shows a decline of ~20% over the span of the observations. There is also flickering and a 27 s (or 54 s) "dwarf nova oscillation," revealed in a power-spectrum analysis. The amplitude of this oscillation is larger at shorter wavelengths. We assemble and illustrate the spectral energy distribution of AM CVn from the ultraviolet to the near-infrared. Modeling the accretion phenomenon in this binary system can in principle lead to a robust estimate of the mass accretion rate on to the central white dwarf, which is of great interest in characterizing the evolutionary history of the binary system. Inferences about the mass accretion rate depend strongly on the local radiative properties of the disk, as we illustrate. Uncertainty in the distance of AM CVn and other parameters of the binary system currently limit the ability to confidently infer the mass accretion rate. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555. These observations are associated with program 8159.

  12. X-ray crystal structure of divalent metal-activated ß-xyloisdase, RS223BX

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the first X-ray structure of a glycoside hydrolase family 43 ß-xylosidase, RS223BX, which is strongly activated by the addition of divalent metal cations. The 2.69 Å structure reveals that the Ca2+ cation is located at the back of the active site pocket. The Ca2+ coordinates to H274 to sta...

  13. RS-34 Phoenix In-Space Propulsion System Applied to Active Debris Removal Mission

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Burnside, Christopher G.

    2014-01-01

    In-space propulsion is a high percentage of the cost when considering Active Debris Removal mission. For this reason it is desired to research if existing designs with slight modification would meet mission requirements to aid in reducing cost of the overall mission. Such a system capable of rendezvous, close proximity operations, and de-orbit of Envisat class resident space objects has been identified in the existing RS-34 Phoenix. RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper program; specifically the pressure-fed storable bi-propellant Stage IV Post Boost Propulsion System. The National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC has obtained permission from the USAF to obtain all the remaining RS-34 stages for re-use opportunities. The MSFC Advanced Concepts Office (ACO) was commissioned to lead a study for evaluation of the Rocketdyne produced RS-34 propulsion system as it applies to an active debris removal design reference mission for resident space object targets including Envisat. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy payloads at multiple orbital locations. The RS-34 Concept Study lead by sought to further understand application for a similar orbital debris design reference mission to provide propulsive capability for rendezvous, close proximity operations to support the capture phase of the mission, and deorbit of single or multiple large class resident space objects. Multiple configurations varying the degree of modification were identified to trade for dry mass optimization and

  14. Anti Pneumococcal Activity of Azithromycin-Eudragit RS100 Nano-Formulations

    PubMed Central

    Adibkia, Khosro; Khorasani, Golrokh; Payab, Shahriar; Lotfipour, Farzaneh

    2016-01-01

    Purpose: Bacterial pneumonia is a common lung infection caused by different types of bacteria. Azithromycin (AZI), an azalide antibiotic, is widely used to manage pneumococcal infections. Studies have shown that antibiotics in nanocarriers may lead to increased antibacterial activity and reduced toxicity. The aim of this work was to valuate in vitro antibacterial performance azithromycin-Eudragit RS100 nano-formulations against Streptococcus pneumoniae and Staphylococcus aureus. Methods: AZI-Eudragit RS100 nanoparticles were prepared via electrospinning technique and the in vitro antibacterial performance against S. pneumoniae and S. aureus were assessed using agar dilution method. Results: Nanofibers in the sizes about 100-300 nm in diameter and micro scale in length and nanobeads in the range of 100-500 nm were achieved. The Minimum Inhibitory Concentrations (MIC) showed an enhancement in the antimicrobial effect of AZI-Eudragit RS100 nanofibers (40 µg/ml) compare to untreated AZI solution (>160 µg/ml) against S. pneumonia. The MIC value for AZI-Eudragit RS100 nanofibers against S. aureus was >128 µg/ml, same as that of the untreated AZI solution. Conclusion: The enhanced efficiency of AZI in nanofibers could be related to the more adsorption opportunity of nanofibers to S. pneumonia capsulated cell wall which provides an antibiotic depot on the bacterial surface compared to S. aureus. AZI-Eudragit RS100 nanofibers with enhanced antimicrobial effect against S. pneumonia can be considered as a candidate for in vivo evaluations in antibiotic therapy of Pneumococcal infections. PMID:27766231

  15. DHPG Activation of Group 1 mGluRs in BLA Enhances Fear Conditioning

    ERIC Educational Resources Information Center

    Rudy, Jerry W.; Matus-Amat, Patricia

    2009-01-01

    Group 1 metabotropic glutamate receptors are known to play an important role in both synaptic plasticity and memory. We show that activating these receptors prior to fear conditioning by infusing the group 1 mGluR agonist, (R.S.)-3,5-dihydroxyphenylglycine (DHPG), into the basolateral region of the amygdala (BLA) of adult Sprague-Dawley rats…

  16. TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 gene polymorphisms as possible risk factor for rheumatoid arthritis: relation to activity and severity.

    PubMed

    Mosaad, Y M; El-Bassiony, S R; El-Ghaweet, A E; Elhindawy, M M; El-Deek, B S; Sultan, W A

    2015-08-01

    This study was aimed to evaluate the impact of both TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 polymorphisms on susceptibility to rheumatoid arthritis (RA) in a cohort of Egyptian population and to evaluate for the first time their relation to activity, severity, disease-related disability and erosion. TIM-1 rs41297579 G>A (-1454) and TIM-4 rs7700944 gene polymorphisms were typed by RFLP for 128 patients with RA and 125 healthy controls. The A allele, A-containing genotypes (GA and AA) of the TIM-4 and GA haplotype were present with significant higher frequency in patients with RA than healthy controls (Pc  < 0.001). These findings suggest that the A allele, A-containing genotypes (GA and AA) and GA haplotype may be a susceptibility risk factor for RA [OR = 5.83 (3.6-9.4), OR = 9.41 (5.0-17.6) and OR = 4.21 (1.07-19.2), respectively]. No associations were found between TIM genotypes and disease activity, severity or presence of erosion. However, the RA patients with GA genotype of TIM-4 have higher grade of rheumatoid factor (RF) positivity (P = 0.018), and have worse disease-related disability (P = 0.007) and worse pain (0.025). TIM-4 rs7700944 and not TIM-1 rs41297579 G>A (-1454) is associated with RA in the present cohort of Egyptian and may be a risk factor for development of RA in Egyptian. Both SNPs have no effect on disease activity, severity or erosion. However, TIM-4 GA genotype is associated with higher grade of RF positivity and worse disease-related disability and pain.

  17. The Formation of EL CVn-type Binaries

    NASA Astrophysics Data System (ADS)

    Chen, Xuefei; Maxted, P. F. L.; Li, Jiao; Han, Zhanwen

    2017-01-01

    EL CVn-type binaries are eclipsing binaries that contain an A- or F-type dwarf star and a very low mass (˜0.2M⊙) helium white dwarf precursor (proto-He WD). A number of such objects have been discovered in the WASP and Kepler photometric surveys. Here we have studied the formation of EL CVn-type binaries and give the properties and the space density of this population of stars in the Galaxy. We show that EL CVn binaries cannot be produced by common envelope evolution as previously believed because this process leads to merging of the components when giants have such low-mass cores. Stable mass transfer in low-mass binaries, from more than 65,000 runs of Population I binary evolution, may well reproduce the properties of EL CVn stars such as the evolutionary phase, mass ratios and the WD mass-period (MWD - P) relation. The study shows that the most common donor mass range for producing the observed EL CVn-type stars is 1.15 - 1.20M⊙ and that the lifetime of such objects increases dramatically with decreasing proto-He WD mass. This leads to an intrinsic peak mass around the minimum mass of proto-He WDs of ˜0.16M⊙. The most probable proto-He WD mass is 0.17 - 0.21M⊙ after selection effects included. We estimated the number of EL CVn stars with P ≤ 2.2 d to be 2 - 5 × 106 in the Galaxy, indicating a local density of 4 - 10 × 10-6pc-3. We conclude that many more EL CVn-type binaries remain to be discovered and that these binaries will be predominantly low-mass systems in old stellar populations.

  18. Bitter peptides activate hTAS2Rs, the human bitter receptors

    PubMed Central

    Maehashi, Kenji; Matano, Mami; Wang, Hong; Vo, Lynn A.; Yamamoto, Yasushi; Huang, Liquan

    2008-01-01

    Fermented food contains numerous peptides derived from material proteins. Bitter peptides formed during the fermentation process are responsible for the bitter taste of fermented food. We investigated whether human bitter receptors (hTAS2Rs) recognize bitterness of peptides with a heterologous expression system. HEK293 cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 responded to bitter casein digests. Among those cells, the hTAS2R1-expressing cell was most strongly activated by the synthesized bitter peptides Gly-Phe and Gly-Leu, and none of the cells was activated by the non-bitter dipeptide Gly-Gly. The results showed that these bitter peptides, as well as many other bitter compounds, activate hTAS2Rs, suggesting that humans utilize these hTAS2Rs to recognize and perceive the structure and bitterness of peptides. PMID:18037373

  19. An Analysis of Light Variations of RS Canum Venaticorum Binary Systems.

    NASA Astrophysics Data System (ADS)

    Caton, Daniel Bruce

    Photoelectric data for fourteen RS Canum Venaticorum binary systems were obtained by the author from 1978 through 1981, at Rosemary Hill Observatory. These data are presented in the form of light curves and tabulated magnitudes and heliocentric Julian Dates. The outside-of-eclipse points for eight systems were Fourier analyzed for measurement of any distortion wave in the light curve. The wave in RS Canum Venaticorum itself was found to have moved half a phase unit in only two years. A wave was discovered in the light curve of RZ Eridani, and was found to have changed in a manner consistent with the starspot model for RS CVn systems. The light curve for UX Comae Bernices was found to have a large amount of intrinsic scatter, and the system was found to be anomalously bright on one night. These characteristics suggest that some type of flare activity may be present in that system. The other five systems analyzed were found to have waves consistent with other published results, or to have no definite wave at all. The possibility of detecting spots and deriving spot sizes from secondary eclipse observations was also explored. For this purpose the Wilson-Devinney computer program for light curve synthesis was modified to allow spots on the secondary star. Comparison of computer synthesized secondary eclipses of spotted stars to actual observations showed that there is little chance of detecting fluctuations due to individual spots. It was found that there is even less chance for discriminating between a few large spots and a large number of smaller spots. However, the program did produce good fits to RS CVn light curves, using reasonable spot parameters.

  20. A light-curve distortion-wave analysis of eight RS Canum Venaticorum systems

    NASA Astrophysics Data System (ADS)

    Caton, D. B.

    1986-01-01

    A program of differential U,B,V photometry of 14 RS CVn systems carried out at Rosemary Hill Observatory in 1978 - 1981 is described, and an analysis of the light curves for the characteristic distortion wave for eight of the systems is presented. The V light curves of the systems are shown. Significant waves were observed in RS CVn, RZ Eri, and RW UMa. No significant waves were found in UX Com, GK Hya, AR Lac, LX Per, or TY Pyx. Unusual light curve distortions were observed in UX Com and AR Lac.

  1. Polymorphism rs7278468 is associated with Age-related cataract through decreasing transcriptional activity of the CRYAA promoter.

    PubMed

    Ma, Xiaoyin; Jiao, Xiaodong; Ma, Zhiwei; Hejtmancik, J Fielding

    2016-03-17

    CRYAA plays critical functional roles in lens transparency and opacity, and polymorphisms near CRYAA have been associated with age-related cataract (ARC). This study examines polymorphisms in the CRYAA promoter region for association with ARC and elucidates the mechanisms of this association. Three SNPs nominally associated with ARC were identified in the promoter region of CRYAA: rs3761382 (P = 0.06, OR (Odds ratio) = 1.5), rs13053109 (P = 0.04, OR = 1.6), rs7278468 (P = 0.007, OR = 0.6). The C-G-T haplotype increased the risk for ARC overall (P = 0.005, OR = 1.8), and both alleles and haplotypes show a stronger association with cortical cataract (rs3761382, P = 0.002, OR = 2.1; rs13053109, P = 0.002, OR = 2.1; rs7278468, P = 0.0007, OR = 0.5; C-G-T haplotype, P = 0.0003, OR = 2.2). The C-G-T risk haplotype decreased transcriptional activity through rs7278468, which lies in a consensus binding site for the transcription repressor KLF10. KLF10 binding inhibited CRYAA transcription, and both binding and inhibition were greater with the T rs7278468 allele. Knockdown of KLF10 in HLE cells partially rescued the transcriptional activity of CRYAA with rs7278468 T allele, but did not affect activity with the G allele. Thus, our data suggest that the T allele of rs7278468 in the CRYAA promoter is associated with ARC through increasing binding of KLF-10 and thus decreasing CRYAA transcription.

  2. Calprotectin Increases the Activity of the SaeRS Two Component System and Murine Mortality during Staphylococcus aureus Infections.

    PubMed

    Cho, Hoonsik; Jeong, Do-Won; Liu, Qian; Yeo, Won-Sik; Vogl, Thomas; Skaar, Eric P; Chazin, Walter J; Bae, Taeok

    2015-07-01

    Calprotectin, the most abundant cytoplasmic protein in neutrophils, suppresses the growth of Staphylococcus aureus by sequestering the nutrient metal ions Zn and Mn. Here we show that calprotectin can also enhance the activity of the SaeRS two component system (TCS), a signaling system essential for production of over 20 virulence factors in S. aureus. The activity of the SaeRS TCS is repressed by certain divalent ions found in blood or neutrophil granules; however, the Zn bound-form of calprotectin relieves this repression. During staphylococcal encounter with murine neutrophils or staphylococcal infection of the murine peritoneal cavity, calprotectin increases the activity of the SaeRS TCS as well as the production of proinflammatory cytokines such as IL-1β and TNF-α, resulting in higher murine mortality. These results suggest that, under certain conditions, calprotectin can be exploited by S. aureus to increase bacterial virulence and host mortality.

  3. Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs.

    PubMed

    Sanderson, Thomas M; Collingridge, Graham L; Fitzjohn, Stephen M

    2011-07-27

    The removal of AMPA receptors from synapses is a major component of long-term depression (LTD). How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2) expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses). In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP) inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

  4. Hyperphosphorylation of RyRs Underlies Triggered Activity in Transgenic Rabbit Model of LQT2 Syndrome

    PubMed Central

    Terentyev, Dmitry; Rees, Colin M.; Li, Weiyan; Cooper, Leroy L.; Jindal, Hitesh K.; Peng, Xuwen; Lu, Yichun; Terentyeva, Radmila; Odening, Katja E.; Daley, Jean; Bist, Kamana; Choi, Bum-Rak; Karma, Alain; Koren, Gideon

    2015-01-01

    Rationale Loss-of function mutations in HERG potassium channels underlie long QT syndrome (LQTS) type 2 (LQT2), and are associated with fatal ventricular tachyarrhythmia. Previously, most studies focused on plasmamembrane-related pathways involved in arrhythmogenesis in LQTS, while pro-arrhythmic changes in intracellular Ca2+ handling remained unexplored. Objective We investigated the remodeling of Ca2+ homeostasis in ventricular cardiomyocytes derived from transgenic rabbit model of LQT2 in order to determine whether these changes contribute to triggered activity in the form of early afterdepolarizations (EADs). Methods and Results Confocal Ca2+ imaging revealed decrease in amplitude of Ca2+ transients and SR Ca2+ content in LQT2 myocytes. Experiments using SR-entrapped Ca2+ indicator demonstrated enhanced RyR-mediated SR Ca2+ leak in LQT2 cells. Western blot analyses showed increased phosphorylation of RyR in LQT2 myocytes vs. controls. Co-immunoprecipitation experiments demonstrated loss of protein phosphatases type 1 and type 2 from the RyR complex. Stimulation of LQT2 cells with β-adrenergic agonist isoproterenol resulted in prolongation of the plateau of action potentials accompanied by aberrant Ca2+ releases and EADs, which were abolished by inhibition of CaMKII. Computer simulations showed that late aberrant Ca2+ releases caused by RyR hyperactivity promote EADs and underlie the enhanced triggered activity through increased forward mode of NCX1. Conclusions Hyperactive, hyperphosphorylated RyRs due to reduced local phosphatase activity enhance triggered activity in LQT2 syndrome. EADs are promoted by aberrant RyR-mediated Ca2+ releases that are present despite a reduction of sarcoplasmic reticulum (SR) content. Those releases increase forward mode NCX1, thereby slowing repolarization and enabling L-type Ca2+ current reactivation. PMID:25249569

  5. Self-assembly of chiral nanoparticle pyramids with strong R/S optical activity.

    PubMed

    Yan, Wenjing; Xu, Liguang; Xu, Chuanlai; Ma, Wei; Kuang, Hua; Wang, Libing; Kotov, Nicholas A

    2012-09-12

    Chirality at the nanometer scale represents one of the most rapidly developing areas of research. Self-assembly of DNA-nanoparticle (NP) hybrids enables geometrically precise assembly of chiral isomers. The concept of a discrete chiral nanostructure of tetrahedral shape and topology fabricated from four different NPs located in the corners of the pyramid is fundamental to the field. While the first observations of optical activity of mixed pyramidal assemblies were made in 2009 (Chen, W.; Nano Lett. 2009, 9, 2153-2159), further studies are difficult without finely resolved optical data for precisely organized NP pyramidal enantiomers. Here we describe the preparation of a family of self-assembled chiral pyramids made from multiple metal and/or semiconductor NPs with a yield as high as 80%. Purposefully made R- and S-enantiomers of chiral pyramids with four different NPs from three different materials displayed strong chiroptical activity, with anisotropy g-factors as high as 1.9 × 10(-2) in the visible spectral range. Importantly, all NP constituents contribute to the chiroptical activity of the R/S pyramids. We were able to observe three different circular dichroism signals in the range of 350-550 nm simultaneously. They correspond to the plasmonic oscillations of gold, silver, and bandgap transitions of quantum dots. Tunability of chiroptical bands related to these transitions is essential from fundamental and practical points of view. The predictability of optical properties of pyramids, the simplicity of their self-assembly in comparison with lithography, and the possibility for polymerase chain reaction-based automation of their synthesis are expected to facilitate their future applications.

  6. Growth phase-dependent activation of the DccRS regulon of Campylobacter jejuni

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two-component systems are widespread prokaryotic signal transduction devices which allow the regulation of cellular functions in response to changing environmental conditions. The two-component system DccRS (Cj1223-Cj1222) of Campylobacter jejuni is important for the colonization of chickens. Here w...

  7. Escherichia coli avoids high dissolved oxygen stress by activation of SoxRS and manganese-superoxide dismutase

    PubMed Central

    2013-01-01

    Background High concentrations of reactive oxygen species (ROS) were reported to cause oxidative stress to E. coli cells associated with reduced or inhibited growth. The high ROS concentrations described in these reports were generated by exposing the bacteria to H2O2 and superoxide-generating chemicals which are non-physiological growth conditions. However, the effect of molecular oxygen on oxidative stress response has not been evaluated. Since the use of oxygen-enriched air is a common strategy to support high density growth of E. coli, it was important to investigate the effect of high dissolved oxygen concentrations on the physiology and growth of E. coli and the way it responds to oxidative stress. Results To determine the effect of elevated oxygen concentrations on the growth characteristics, specific gene expression and enzyme activity in E. coli, the parental and SOD-deficient strain were evaluated when the dissolved oxygen (dO2) level was increased from 30% to 300%. No significant differences in the growth parameters were observed in the parental strain except for a temporary decrease of the respiration and acetate accumulation profile. By performing transcriptional analysis, it was determined that the parental strain responded to the oxidative stress by activating the SoxRS regulon. However, following the dO2 switch, the SOD-deficient strain activated both the SoxRS and OxyR regulons but it was unable to resume its initial growth rate. Conclusion The transcriptional analysis and enzyme activity results indicated that when E. coli is exposed to dO2 shift, the superoxide stress regulator SoxRS is activated and causes the stimulation of the superoxide dismutase system. This enables the E. coli to protect itself from the poisoning effects of oxygen. The OxyR protecting system was not activated, indicating that H2O2 did not increase to stressing levels. PMID:23497217

  8. Nicotine activates YAP1 through nAChRs mediated signaling in esophageal squamous cell cancer (ESCC).

    PubMed

    Zhao, Yue; Zhou, Wei; Xue, Liyan; Zhang, Weimin; Zhan, Qimin

    2014-01-01

    Cigarette smoking is an established risk factor for esophageal cancers. Yes-associated protein 1 (YAP1), the key transcription factor of the mammalian Hippo pathway, has been reported to be an oncogenic factor for many cancers. In this study, we find nicotine administration can induce nuclear translocation and activation of YAP1 in ESCC. Consistently, we observed nuclear translocation and activation of YAP1 by knockdown of CHRNA3, which is a negative regulator of nicotine signaling in bronchial and esophageal cancer cells. Nicotine administration or CHRNA3 depletion substantially increased proliferation and migration in esophageal cancer cells. Interestingly, we find that YAP1 physically interacts with nAChRs, and nAChRs-signaling dissociates YAP1 from its negative regulatory complex composed with α-catenin, β-catenin and 14-3-3 in the cytoplasm, leading to upregulation and nuclear translocation of YAP1. This process likely requires PKC activation, as PKC specific inhibitor Enzastaurin can block nicotine induced YAP1 activation. In addition, we find nicotine signaling also inhibits the interaction of YAP1 with P63, which contributes to the inhibitory effect of nicotine on apoptosis. Using immunohistochemistry analysis we observed upregulation of YAP1 in a significant portion of esophageal cancer samples. Consistently, we have found a significant association between YAP1 upregulation and cigarette smoking in the clinical esophageal cancer samples. Together, these findings suggest that the nicotine activated nAChRs signaling pathway which further activates YAP1 plays an important role in the development of esophageal cancer, and this mechanism may be of a general significance for the carcinogenesis of smoking related cancers.

  9. The pharmacological activity of nicotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery.

    PubMed

    Papke, Roger L; Dwoskin, Linda P; Crooks, Peter A

    2007-04-01

    Cigarette smoking and other forms of tobacco use deliver an array of pharmacologically active alkaloids, including nicotine and ultimately various metabolites of these substances. While nornicotine is a significant component in tobacco as well as a minor systemic metabolite of nicotine, nornicotine appears to be N-demethylated locally in the brain where it accumulates at relatively high levels after chronic nicotine administration. We have now examined the effects of nornicotine on specific combinations of neuronal nicotinic acetylcholine receptor (nAChR) subunits expressed in Xenopus oocytes and compared these responses to those evoked by acetylcholine and nicotine. Of the nAChR subtypes studied, we have found that alpha7 receptors are very responsive to nornicotine (EC50 approximately 17 micromol/L I(max) 50%, compared with acetylcholine (ACh)). nAChRs containing the ligand-binding domain of the alpha6 subunits (in the form of an alpha6/alpha3 chimera) are also strongly responsive to nornicotine (EC50 approximately 4 micromol/L I(max) 50%, compared with ACh). Alpha7-type nAChRs have been suggested to be potential therapeutic targets for Alzheimer's disease, schizophrenia and possibly other pathologies. nAChRs containing alpha6 subunits have been suggested to have a role in nicotine-evoked dopamine release. Thus, understanding the actions of nornicotine in the brain may have significance for both emerging therapeutics and the management of nicotine dependence.

  10. Gaia14aae: the First Fully-Eclipsing AM CVn

    NASA Astrophysics Data System (ADS)

    Green, M. J.; Marsh, T. R.; Steeghs, D. T. H.; Breedt, E.; Campbell, H. C.; Dhillon, V. S.; Hardy, L. K.; Littlefair, S. P.

    2017-03-01

    AM CVns are a class of cataclysmic variables consisting of a white dwarf accreting H-deficient matter from a donor star. With periods of 5 to 65 minutes, AM CVns include the shortest period binaries containing white dwarfs. AM CVns are believed to form by one of three formation channels which can in principle be distinguished by the nature of the donor star, but are difficult to constrain observationally. Gaia14aae was one of the first transients discovered by the Gaia Science Alerts project. It eclipses on a period of 50 minutes, and is the only known AM CVn in which the white dwarf is fully eclipsed. This makes it an attractive system for parameter studies. We present an update on our attempts to measure these properties, using high-speed multi-colour photometry. Preliminary results suggest that the donor star is not as degenerate as predicted by models of white dwarf donors.

  11. Peroxisome proliferator-activated receptor gamma (PPARG) rs1801282 C>G polymorphism is associated with cancer susceptibility in asians: an updated meta-analysis

    PubMed Central

    Wang, Yafeng; Chen, Yu; Jiang, Heping; Tang, Weifeng; Kang, Mingqiang; Liu, Tianyun; Guo, Zengqing; Ma, Zhiqiang

    2015-01-01

    Peroxisome proliferator-activated receptor gamma (PPARG) is related to inflammation and plays an important role in the development of cancer. PPARG rs1801282 C>G polymorphism might influence the risk of cancer by regulating production of PPARG gene. Hence, a comprehensive meta-analysis was conducted to explore the association of PPARG rs1801282 C>G polymorphism with cancer susceptibility. An extensive search of PubMed and Embase databases for all relevant publications was carried out. A total of 38 publications with 16,844 cancer cases and 23,736 controls for PPARG rs1801282 C>G polymorphism were recruited in our study. Our results indicated that PPARG rs1801282 C>G variants were associated with an increased cancer risk in Asian populations and gastric cancer. In summary, the findings suggest that PPARG rs1801282 C>G polymorphism may play a crucial role in malignant transformation and the development of cancer. PMID:26550180

  12. The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide

    PubMed Central

    Gu, Mianzhi; Imlay, James A.

    2011-01-01

    When Escherichia coli is exposed to redox-cycling drugs, its SoxR transcription factor is activated by oxidation of its [2Fe–2S] cluster. In aerobic cells these drugs generate superoxide, and because superoxide dismutase (SOD) is a member of the SoxRS regulon, superoxide was initially thought to be the activator of SoxR. Its many-gene regulon was therefore believed to comprise a defense against superoxide stress. However, we found that abundant superoxide did not effectively activate SoxR in an SOD− mutant, that overproduced SOD could not suppress activation by redox-cycling drugs, and that redox-cycling drugs were able to activate SoxR in anaerobic cells as long as alternative respiratory acceptors were provided. Thus superoxide is not the signal that SoxR senses. Indeed, redox-cycling drugs directly oxidized the cluster of purified SoxR in vitro, while superoxide did not. Redox-cycling drugs are excreted by both bacteria and plants. Their toxicity does not require superoxide, as they poisoned E. coli under anaerobic conditions, in part by oxidizing dehydratase iron-sulfur clusters. Under these conditions SoxRS induction was protective. Thus it is physiologically appropriate that the SoxR protein directly senses redox-cycling drugs rather than superoxide. PMID:21226770

  13. Very Bright, Very Hot and Very Long: Swift Observations of the DG CVn "Superflare" of April 23rd, 2014

    NASA Astrophysics Data System (ADS)

    Drake, Stephen Alan; Osten, Rachel A.; Page, Kim L; Kennea, Jamie A; Oates, Samantha R; Krimm, Hans A; Gehrels, Neil; Page, Mathew J; Kowalski, Adam

    2014-08-01

    On April 23rd this year, one of the 2 stars in the close visual binary dM4e system DG CVn flared to a level bright enough 300 milliCrab in the 15-150 keV band) that it triggered the Swift Burst Alert Telescope. Two minutes later, after Swift had slewed to the direction of this source, the Swift X-ray Telescope (XRT) and the Ultraviolet Optical Telescope (UVOT) commenced observing this flare. These observations continued (intermittently) for about 20 days and yielded a fascinating case history of this colossal event, the decay of which took more than a week in the UV and soft X-ray regions, and included several smaller superimposed secondary flares. The peak 0.3-10 keV luminosity observed by the XRT of 1.9e32 erg/s at the 18 pc distance of this system is 1.5 times the 'normal' combined systemic bolometric luminosity of 1.3e32 erg/s, making this event a super-bolometric flare similar to the 2008 flare of EV Lac (also detected by Swift). The BAT and XRT spectra of this flare in the first 6 minutes indicate that the emission was dominated by very hot (>>10 keV) plasma and/or a non-thermal power-law emission. This flare is arguably the longest, most X-ray luminous and hottest flare ever seen for an M dwarf in the solar neighborhood, and is reminiscent of the 9 days long flare of the RS CVn binary CF Tuc detected by ROSAT. We discuss how these exceptional characteristics may be related to the known properties of this system, specifically to its youth (30 Myr) and rapid rotation (55 km/s).

  14. Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

    DTIC Science & Technology

    2013-10-22

    ported around the shipyard and the weight of a unit module that can be lifted by the gantry crane into the drydock. However, on CVN 78, more...independently erected into the drydock, helping to alleviate demands on the gantry drydock crane and decreasing the number of times welders have to...perlifts- Prior to construction ofCVN 78, the lifting capacity of the gantry crane used to erect superlifts was increased from 900 to 1050 tons. While

  15. The ZOG Technology Demonstration Project: A System Evaluation of USS CARL VINSON (CVN 70)

    DTIC Science & Technology

    1984-12-01

    rNPRDC TR 85-14 DECEMBER 1984 ~JI 00o THE ZOG TECHNOLOGY DEMONSTRATION PROJECT : 00 A SYSTEM EVALUATION OF USS CARL VINSON ICVN 70) Lfl Reproduced...California 92152 NPR.DC TR 85-14 December 1984 THE ZOG TECHNOLOGY DEMONSTRATION PROJECT : A SYSTEM EVALUATION ON USS CARL VINSON (CVN 70) Nicholas H...ZOG TECHNOLOGY DEMONSTRATION PROJECT : A SYSTEM EVALUATION ON THE USS CARL VINSON (CVN 70) Van Matre, Nicholas; Moy, Melvyn, C.; McCann, Patrick, H

  16. CVN 68 Class Displacement Concerns; Dealing with the Differences between the Modeled and Actual Displacements

    DTIC Science & Technology

    2009-09-01

    Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE September 2009 3. REPORT TYPE AND...CVN 68 class aircraft carriers are actually exceeding displacement limits based on NAVSEA projections . The NAVSEA projections are based on...values collected from all commissioned CVN 68 class aircraft carriers. Analysis reveals that the NAVSEA projections are predicting the carrier’s

  17. Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

    DTIC Science & Technology

    2016-05-27

    Names Next Aircraft Carrier USS John F. Kennedy,” Navy News Service, May 29, 2011, accessed online on June 1, 2011 at http://www.navy.mil/search...and USS John F. Kennedy (CVN 79) come online ? A: The proposed plan matches the number of complete carrier air wings to the number of operationally...efficiently be performed. The CVN 79 build sequence installs 20 percent more parts in shop , and 30 percent more parts on the final assembly platen, as

  18. Navy Ford (CVN 78) Class Aircraft Carrier Program: Background and Issues for Congress

    DTIC Science & Technology

    2016-05-27

    Names Next Aircraft Carrier USS John F. Kennedy,” Navy News Service, May 29, 2011, accessed online on June 1, 2011 at http://www.navy.mil/search...and USS John F. Kennedy (CVN 79) come online ? A: The proposed plan matches the number of complete carrier air wings to the number of operationally...efficiently be performed. The CVN 79 build sequence installs 20 percent more parts in shop , and 30 percent more parts on the final assembly platen, as

  19. He-accreting WDs: AM CVn stars with WD donors

    NASA Astrophysics Data System (ADS)

    Piersanti, L.; Yungelson, L. R.; Tornambé, A.

    2015-09-01

    We study the physical and evolutionary properties of the `white dwarf (WD) family' of AM CVn stars by computing realistic models of interacting double-degenerate systems. We evaluate self-consistently both the mass-transfer rate from the donor, as determined by gravitational wave emission and interaction with the binary companion, and the thermal response of the accretor to mass deposition. We find that, after the onset of mass transfer, all the considered systems undergo a strong non-dynamical He-flash. However, due to the compactness of these systems, the expanding accretors fill their Roche lobe very soon, thus preventing the efficient heating of the external layers of the accreted CO WDs. Moreover, due to the loss of matter from the systems, the orbital separations enlarge and mass transfer comes to a halt. The further evolution depends on the value of dot{M} after the donors fill again their lobe. On one hand, if the accretion rate, as determined by the actual value of (Mdon, Macc), is high enough, the accretors experience several He-flashes of decreasing strength and then quiescent He-burning sets in. Later on, since the mass-transfer rate in IDD is a permanently decreasing function of time, accretors experience several recurrent strong flashes. On the other hand, for intermediate and low values of dot{M} the accretors enter directly the strong flashes accretion regime. As expected, in all the considered systems the last He-flash is the strongest one, even if the physical conditions suitable for a dynamical event are never attained. When the mass accretion rate decreases below (2-3) × 10-8 M⊙ yr-1, the compressional heating of the He-shell becomes less efficient than the neutrino cooling, so that all the accretors in the considered systems evolve into massive degenerate objects. Our results suggest that SNe .Ia or Type Ia Supernovae due to Edge-Lit Detonation in the WD family of AM CVn stars should be much more rare than previously expected.

  20. Activation of Functional α7-Containing nAChRs in Hippocampal CA1 Pyramidal Neurons by Physiological Levels of Choline in the Presence of PNU-120596

    PubMed Central

    Kalappa, Bopanna I.; Gusev, Alexander G.; Uteshev, Victor V.

    2010-01-01

    Background The level of expression of functional α7-containing nicotinic acetylcholine receptors (nAChRs) in hippocampal CA1 pyramidal neurons is believed to be very low compared to hippocampal CA1 interneurons, and for many years this expression was largely overlooked. However, high densities of expression of functional α7-containing nAChRs in CA1 pyramidal neurons may not be necessary for triggering important cellular and network functions, especially if activation of α7-containing nAChRs occurs in the presence of positive allosteric modulators such as PNU-120596. Methodology/Principal Findings An approach previously developed for α7-containing nAChRs expressed in tuberomammillary neurons was applied to investigate functional CA1 pyramidal α7-containing nAChRs using rat coronal hippocampal slices and patch-clamp electrophysiology. The majority (∼71%) of tested CA1 pyramidal neurons expressed low densities of functional α7-containing nAChRs as evidenced by small whole-cell responses to choline, a selective endogenous agonist of α7 nAChRs. These responses were potentiated by PNU-120596, a novel positive allosteric modulator of α7 nAChRs. The density of functional α7-containing nAChRs expressed in CA1 pyramidal neurons (and thus, the normalized net effect of activation, i.e., response net charge per unit of membrane capacitance per unit of time) was estimated to be ∼5% of the density observed in CA1 interneurons. The results of this study demonstrate that despite low levels of expression of functional pyramidal α7-containing nAChRs, physiological levels of choline (∼10 µM) are sufficient to activate these receptors and transiently depolarize and even excite CA1 pyramidal neurons in the presence of PNU-120596. The observed effects are possible because in the presence of 10 µM choline and 1–5 µM PNU-120596, a single opening of an individual pyramidal α7-containing nAChR ion channel appears to transiently depolarize (∼4 mV) the entire pyramidal

  1. The evolution of magnetic activity on V711 Tauri and evidence for a significant facular contribution

    NASA Technical Reports Server (NTRS)

    Dorren, J. D.; Guinan, E. F.

    1990-01-01

    The nature of the long-term evolution of magnetic activity in the RS CVn binary V711 Tauri is investigated using the complete set of available archival IUE SWP low-dispersion spectra of V711 Tau for the period covering August 1978 - December 1984. An analysis of the spectra confirmed the pattern of a long-term smooth variation of chromospheric and transition region emission found previosly by Dorren et al. (1986). An explanation of the relationship between the different facets of the magnetic activity on V711 Tau is presented.

  2. Pharmacological characterization of RS-1259, an orally active dual inhibitor of acetylcholinesterase and serotonin transporter, in rodents: possible treatment of Alzheimer's disease.

    PubMed

    Abe, Yasuyuki; Aoyagi, Atsushi; Hara, Takao; Abe, Kazumi; Yamazaki, Reina; Kumagae, Yoshihiro; Naruto, Shunji; Koyama, Kazuo; Marumoto, Shinji; Tago, Keiko; Toda, Narihiro; Takami, Kazuko; Yamada, Naho; Ori, Mayuko; Kogen, Hiroshi; Kaneko, Tsugio

    2003-09-01

    A dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT), RS-1259 (4-[1S)-methylamino-3-(4-nitrophenoxy)]propylphenyl N,N-dimethylcarbamate (fumaric acid)(1/2)salt), was newly synthesized. RS-1259 simultaneously inhibited AChE and SERT in the brain following an oral administration in mice and rats. Actual simultaneous elevation of extracellular levels of 5-HT and ACh in the rat hippocampus was confirmed by microdialysis. The compound was as effective as SERT inhibitors such as fluoxetine and fluvoxamine in a 5-hydroxytryptophan-enhancing test in mice. Spatial memory deficits in the two-platform task of a water maze in aged rats were ameliorated by RS-1259 as well as donepezil. Both RS-1259 and donepezil increased the awake episodes in the daytime electroencephalogram of rats. Although RS-1259 was weaker than donepezil in enhancing central cholinergic transmission, as observed by ACh elevation in the hippocampus and memory enhancement in aged rats, the efficacy of RS-1259 on the consciousness level, which reflects the whole activity in the brain, was almost the same as that of donepezil. These results suggest that both cholinergic and serotonergic systems are involved in maintaining brain arousal and that a dual inhibitor of AChE and SERT may be useful for the treatment of cognitive disorders associated with reduced brain activity such as in Alzheimer's disease.

  3. The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length.

    PubMed

    Concetti, Fabio; Carpi, Francesco M; Nabissi, Massimo; Picciolini, Matteo; Santoni, Giorgio; Napolioni, Valerio

    2015-02-01

    Recent evidence demonstrated a relevant role of adenosine deaminase (ADA) in replicative senescence of T cells through its capacity to modulate telomerase activity (TA). Herein, we tested the impact of the functional polymorphism ADA rs73598374:G>A (c.22G>A, p.Asp8Asn) on telomere biology, by measuring TA and leukocyte telomere length (LTL) in healthy subjects selected according to rs73598374 genotype. rs73598374-A carriers showed lower TA (P=0.019) and shorter LTL (P=0.003), respectively, compared to G/G carriers. rs73598374-A carriers showed a stronger cross-sectional age reduction of LTL (r=-0.314, P=0.005) compared to G/G carriers (r=-0.243, P=0.022). The reduced ADA activity associated to rs73598374-A variant predisposes those carriers to display higher levels of adenosine compared to G/G carriers. Consequently, it may lead to an accelerated process of replicative senescence, causing a stronger reduction of TA and in turn shorter LTL. In conclusion, the crucial role played by replicative senescence of the immune system in several human diseases and in the aging process underscores the relevance of the present findings and also spurs interest into the possible involvement of rs73598374 in shaping the susceptibility to several age-related diseases.

  4. AM CVn Stars: Structure and Evolution of Ultra-Short Period Interacting Binaries

    NASA Technical Reports Server (NTRS)

    Froning, Cynthia

    2005-01-01

    This is the final report of a FUSE program to study the physics of accretion and outflows in ultra-compact, helium dominated, disk-accreting binaries. With FUSE, we observed the AM CVn binary V803 Cen, which is one of only two AM CVn systems observed by FUSE to date. V803 Cen is a short-period interacting binary in which a hydrogen-deficient white dwarf transfers mass to another white dwarf via a hot, steady-state accretion disk. Unlike other cataclysmic variables (CVs), AM CVn stars have undergone double common envelope evolution (one for each white dwarf in the binary) and so probe an alternate route of evolution in binary stars. Our goals in this project were to investigate how the structure of the accretion disk and the link between the disk and wind outflows are affected by the absence of hydrogen in the system and by the compact size of the binary and the accretion disk.

  5. BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene.

    PubMed

    Rinkwitz, Silke; Geng, Fan-Suo; Manning, Elizabeth; Suster, Maximiliano; Kawakami, Koichi; Becker, Thomas S

    2015-10-01

    Single Nucleotide Polymorphisms in FTO intron 1 have been associated with obesity risk, leading to the hypothesis that FTO is the obesity-related gene. However, other studies have shown that the FTO gene is part of the regulatory domain of the neighboring IRX3 gene and that enhancers in FTO intron 1 regulate IRX3. While Irx3 activity was shown to be necessary in the hypothalamus for the metabolic function of Irx3 in mouse, no enhancers with hypothalamic activity have been demonstrated in the risk-associated region within FTO. In order to identify potential enhancers at the human FTO locus in vivo, we tested regulatory activity in FTO intron 1 using BAC transgenesis in zebrafish. A minimal gata2 promoter-GFP cassette was inserted 1.3 kb upstream of the obesity associated SNP rs9939609 in a human FTO BAC plasmid. In addition to the previously identified expression domains in notochord and kidney, human FTO BAC:GFP transgenic zebrafish larvae expressed GFP in the ventral posterior tuberculum, the posterior hypothalamus and the anterior brainstem, which are also expression domains of zebrafish irx3a. In contrast, an in-frame insertion of a GFP cassette at the FTO start codon resulted in weak ubiquitous GFP expression indicating that the promoter of FTO does likely not react to enhancers located in the obesity risk-associated region.

  6. The ENTPD1 promoter polymorphism -860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk.

    PubMed

    Maloney, James P; Branchford, Brian R; Brodsky, Gary L; Cosmic, Maxwell S; Calabrese, David W; Aquilante, Christina L; Maloney, Kelly W; Gonzalez, Joseph R; Zhang, Weiming; Moreau, Kerrie L; Wiggins, Kerri L; Smith, Nicholas L; Broeckel, Ulrich; Di Paola, Jorge

    2017-03-16

    Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1) degrades the purines ATP and ADP that are key regulators of inflammation and clotting. We hypothesized that NTPDase1 polymorphisms exist and that they regulate this pathway. We sequenced the ENTPD1 gene (encoding NTPDase1) in 216 subjects then assessed genotypes in 2 cohorts comprising 2213 humans to identify ENTPD1 polymorphisms associated with venous thromboembolism (VTE). The G allele of the intron 1 polymorphism rs3176891 was more common in VTE vs. controls (odds ratio 1.26-1.9); it did not affect RNA splicing, but it was in strong linkage disequilibrium with the G allele of the promoter polymorphism rs3814159, which increased transcriptional activity by 8-fold. Oligonucleotides containing the G allele of this promoter region bound nuclear extracts more avidly. Carriers of rs3176891 G had endothelial cells with increased NTPDase1 activity and protein expression, and had platelets with enhanced aggregation. Thus, the G allele of rs3176891 marks a haplotype associated with increased clotting and platelet aggregation attributable to a promoter variant associated with increased transcription, expression, and activity of NTPDase1. We term this gain-of-function phenotype observed with rs3814159 G "CD39 Denver."-Maloney, J. P., Branchford, B. R., Brodsky, G. L., Cosmic, M. S., Calabrese, D. W., Aquilante, C. L., Maloney, K. W., Gonzalez, J. R., Zhang, W., Moreau, K. L., Wiggins, K. L., Smith, N. L., Broeckel, U., Di Paola, J. The ENTPD1 promoter polymorphism -860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk.

  7. RS9, a novel Nrf2 activator, attenuates light-induced death of cells of photoreceptor cells and Müller glia cells.

    PubMed

    Inoue, Yuki; Shimazawa, Masamitsu; Noda, Yasuhiro; Nagano, Ryota; Otsuka, Tomohiro; Kuse, Yoshiki; Nakano, Yukimichi; Tsuruma, Kazuhiro; Nakagami, Yasuhiro; Hara, Hideaki

    2017-03-27

    The retina is highly sensitive to oxidative stress because of its high consumption of oxygen associated with the phototransductional processes. Recent findings have suggested that oxidative stress is involved in the pathology of age-related macular degeneration (AMD), a progressive degeneration of the central retina. A well-known environmental risk factor is light exposure, as excessive and continuous light exposure can damage photoreceptors. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that controls antioxidative responses and phase 2 enzymes. Thus, we hypothesized that RS9, a specific activator of Nrf2, decreases light-induced retinal cell death in vivo and in vitro. Nrf2 was detected in the nucleus of the 661w cells exposed to RS9 and also after light exposure, and the Nrf2-antioxidant response element (ARE) binding was increased in 661w cells after exposure to RS9. Consequentially, the expression of the phase 2 enzyme's mRNAs of Ho-1, Nqo-1, and Gclm genes were increased in 661w cells after exposure to RS9. Further, RS9 decreased the light-induced death of 661W cells (2,500 lx, 24 h), and also reduced the functional damages and the histological degeneration of the nuclei in the outer nuclear layer (ONL) or the retina in the in vivo studies (8,000 lx, 3 h). HO-1 was increased after light exposure, and Nrf2 was translocated into the nucleus after light exposure in vivo. Silencing of Ho-1 reduced the protective effects of RS9 against light-induced death of 661w cells. These findings indicate that RS9 has therapeutic potential for retinal diseases that are aggravated by light exposure. This article is protected by copyright. All rights reserved.

  8. Improved performance of Yarrowia lipolytica lipase-catalyzed kinetic resolution of (R,S)-2-octanol by an integrated strategy of interfacial activation, bioimprinting and immobilization.

    PubMed

    Liu, Ying; Guo, Chen; Sun, Xi-Tong; Liu, Chun-Zhao

    2013-08-01

    Yarrowia lipolytica lipase (YLL) demonstrated an (R)-enantiopreference for efficient resolution of (R,S)-2-octanol. The activity, enantioselectivity, the ratio of substrate to enzyme, acetaldehyde tolerance, and operational stability of YLL were improved by an integrated strategy of interfacial activation, bioimprinting, and immobilization. In comparison with the control, both the enzymatic activity and enantioselectivity increased by a factor of 8.85 and 2.75 by the integrated strategy, respectively. Fifty-one percentage of conversion with 220 of enantioselectivity was obtained using the immobilized YLL prepared by the integrated strategy at a ratio of 104 of substrate to enzyme loaded. The immobilized YLL retained 97% of its initial activity without a decrease in enantioselectivity after 10 successive reuse cycles. Together these results will result in a promising strategy with the YYL for efficient resolution of (R,S)-2-octanol in practice.

  9. Interaction effect between handedness and CNTNAP2 polymorphism (rs7794745 genotype) on voice-specific frontotemporal activity in healthy individuals: an fMRI study

    PubMed Central

    Koeda, Michihiko; Watanabe, Atsushi; Tsuda, Kumiko; Matsumoto, Miwako; Ikeda, Yumiko; Kim, Woochan; Tateno, Amane; Naing, Banyar Than; Karibe, Hiroyuki; Shimada, Takashi; Suzuki, Hidenori; Matsuura, Masato; Okubo, Yoshiro

    2015-01-01

    Recent neuroimaging studies have demonstrated that Contactin-associated protein-like2 (CNTNAP2) polymorphisms affect left-hemispheric function of language processing in healthy individuals, but no study has investigated the influence of these polymorphisms on right-hemispheric function involved in human voice perception. Further, although recent reports suggest that determination of handedness is influenced by genetic effect, the interaction effect between handedness and CNTNAP2 polymorphisms for brain activity in human voice perception and language processing has not been revealed. We aimed to investigate the interaction effect of handedness and CNTNAP2 polymorphisms in respect to brain function for human voice perception and language processing in healthy individuals. Brain function of 108 healthy volunteers (74 right-handed and 34 non-right-handed) was examined while they were passively listening to reverse sentences (rSEN), identifiable non-vocal sounds (SND), and sentences (SEN). Full factorial design analysis was calculated by using three factors: (1) rs7794745 (A/A or A/T), (2) rs2710102 [G/G or A carrier (A/G and A/A)], and (3) voice-specific response (rSEN or SND). The main effect of rs7794745 (A/A or A/T) was significantly revealed at the right middle frontal gyrus (MFG) and bilateral superior temporal gyrus (STG). This result suggests that rs7794745 genotype affects voice-specific brain function. Furthermore, interaction effect was significantly observed among MFG-STG activations by human voice perception, rs7794745 (A/A or A/T), and handedness. These results suggest that CNTNAP2 polymorphisms could be one of the important factors in the neural development related to vocal communication and language processing in both right-handed and non-right-handed healthy individuals. PMID:25941478

  10. STAT4 rs7574865 G/T polymorphism is associated with rheumatoid arthritis and disease activity, but not with anti-CCP antibody levels in a Mexican population.

    PubMed

    Durán-Avelar, Ma de Jesús; Vibanco-Pérez, Norberto; Hernández-Pacheco, Raquel Rocío; Castro-Zambrano, América Del Carmen; Ortiz-Martínez, Liliana; Zambrano-Zaragoza, José Francisco

    2016-12-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease in whose etiology genetic factors are known to play an important role. Among the genes associated with RA, STAT4 could be an important factor in conducting helper T cells toward the pro-inflammatory Th1 and Th17 lineages. The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population. Genotyping was carried out using the Taqman® system from Applied Biosystems in 140 patients with RA and 150 healthy subjects. Disease activity was evaluated by a rheumatologist using the DAS28 and Spanish-HAQ-DI instruments. Anti-CCP levels were determined by ELISA. Associations of the genotypes of rs7574865 with DAS28, HAQ, and anti-CCP antibody levels with RA were determined. Findings showed that the GT and TT genotypes and the T allele from rs7574865 were all associated as risk factors for RA, independently of their anti-CCP status. An association with moderate-to-high disease activity (DAS28 ≥ 3.2) was also found. Additionally, patients with the GT or TT genotypes showed lower HAQ values than those who carried the GG genotype. No differences in anti-CCP antibody levels or DAS28 and genotypes were found. This work supports the association of the STAT4 rs7574865 polymorphism with RA and disease activity, but not with anti-CCP antibody levels in a Mexican population.

  11. A study of short-period RS Canum Venaticorum and W Ursae Majoris binary systems - The global nature of H-alpha

    NASA Astrophysics Data System (ADS)

    Barden, S. C.

    1985-08-01

    The author presents the rotation versus emission characteristics of the Hα line for several short-period (P ⪉ 1d) RS CVn and W UMa binary systems. Estimates for the chromospheric emission arising from each component star were obtained by subtraction of "nonactive" model spectra constructed from comparison stars. Enhanced Hα emission compared to the nonactive comparison stars is seen on all components of the short-period RS CVn systems studied, while a similar enhancement is only typically seen on the primary components of the W-type W UMa systems. A possible correlation between LHα/Lbol and the Rossby number (the ratio between the rotational period and the convective time scale) is seen for those components showing emission.

  12. Endogenous activation of nAChRs and NMDA receptors contributes to the excitability of CA1 stratum radiatum interneurons in rat hippocampal slices: effects of kynurenic acid.

    PubMed

    Alkondon, Manickavasagom; Pereira, Edna F R; Albuquerque, Edson X

    2011-10-15

    CA1 stratum radiatum interneurons (SRIs) express α7 nicotinic receptors (nAChRs) and receive inputs from glutamatergic neurons/axons that express α3β4β2 nAChRs. To test the hypothesis that endogenously active α7 and/or α3β4β2 nAChRs control the excitability of CA1 SRIs in the rat hippocampus, we examined the effects of selective receptor antagonists on spontaneous fast current transients (CTs) recorded from these interneurons under cell-attached configuration. The frequency of CTs, which represent action potentials, increased in the absence of extracellular Mg(2+) and decreased in the presence of the α3β4β2 nAChR antagonist mecamylamine (3 μM) or the NMDA receptor antagonist APV (50 μM). However, it was unaffected by the α7 nAChR antagonist MLA (10 nM) or the AMPA receptor antagonist CNQX (10 μM). Thus, in addition to synaptically and tonically activated NMDA receptors, α3β4β2 nAChRs that are present on glutamatergic axons/neurons synapsing onto SRIs and are activated by basal levels of acetylcholine contribute to the maintenance of the excitability of these interneurons. Kynurenic acid (KYNA), an astrocyte-derived kynurenine metabolite whose levels are increased in the brains of patients with schizophrenia, also controls the excitability of SRIs. At high micromolar concentrations, KYNA, acting primarily as an NMDA receptor antagonist, decreased the CT frequency recorded from the interneurons. At 2 μM, KYNA reduced the CA1 SRI excitability via mechanisms independent of NMDA receptor block. KYNA-induced reduction of excitability of SRIs may contribute to sensory gating deficits that have been attributed to deficient hippocampal GABAergic transmission and high levels of KYNA in the brain of patients with schizophrenia.

  13. Navy Ford (CVN-78) Class Aircraft Carrier Program: Background and Issues for Congress

    DTIC Science & Technology

    2015-12-17

    implications on future carriers in the Ford-class and any subsequent new class of carriers. I also have concerns with manning and berthing on CVN 78. The Navy... berthing . These problems are similar to those seen on other recent ship classes such as DDG 1000 and the Littoral Combat Ship (LCS).... There are...required for delivery, such as berthing spaces for the aviation detachment, and has removed this work from the shipbuilder’s contract. This deferred

  14. Navy Nuclear Aircraft Carrier (CVN) Homeporting at Mayport: Background and Issues for Congress

    DTIC Science & Technology

    2010-12-09

    CVN at Mayport, arguing (as do DOD and the Navy) that the benefits in terms of mitigating risks to the Navy’s Atlantic Fleet CVNs are worth the...proposal, arguing that the benefits in terms of mitigating risks to the Navy’s Atlantic Fleet CVNs are questionable or uncertain, and that the funding...needed to implement the proposal could achieve greater benefits if it were spent on other Navy priorities. The Navy estimates the nonrecurring cost of

  15. Discovery of binarity, spectroscopic frequency analysis, and mode identification of the δ Scuti star 4 CVn

    NASA Astrophysics Data System (ADS)

    Schmid, V. S.; Themeßl, N.; Breger, M.; Degroote, P.; Aerts, C.; Beck, P. G.; Tkachenko, A.; Van Reeth, T.; Bloemen, S.; Debosscher, J.; Castanheira, B. G.; McArthur, B. E.; Pápics, P. I.; Fritz, V.; Falcon, R. E.

    2014-10-01

    More than 40 years of ground-based photometric observations of the δ Sct star 4 CVn has revealed 18 independent oscillation frequencies, including radial as well as non-radial p-modes of low spherical degree ℓ ≤ 2. From 2008 to 2011, more than 2000 spectra were obtained at the 2.1 m Otto-Struve telescope at the McDonald Observatory. We present the analysis of the line-profile variations, based on the Fourier-parameter fit method, detected in the absorption lines of 4 CVn, which carry clear signatures of the pulsations. From a non-sinusoidal, periodic variation of the radial velocities, we discover that 4 CVn is an eccentric binary system with an orbital period Porb = 124.44 ± 0.03 d and an eccentricity e = 0.311 ± 0.003. We detect 20 oscillation frequencies, 9 of which previously unseen in photometric data; attempt mode identification for the two dominant modes, f1 = 7.3764 d-1 and f2 = 5.8496 d-1; and determine the prograde or retrograde nature of 7 of the modes. The projected rotational velocity of the star, veqsini ≃ 106.7 km s-1, translates to a rotation rate of veq/vcrit ≥ 33%. This relatively high rotation rate hampers unique mode identification, since higher order effects of rotation are not included in the current methodology. We conclude that, in order to achieve unambiguous mode identification for 4 CVn, a complete description of rotation and the use of blended lines have to be included in mode-identification techniques. This paper includes data taken at The McDonald Observatory of The University of Texas at Austin.The software package FAMIAS, developed in the framework of the FP6 European Coordination Action HELAS (http://www.helas-eu.org/), has been used in this research.Appendices are available in electronic form at http://www.aanda.org

  16. What Simulations Tell Us About White Dwarf Evolution in AM CVn Close Binaries

    NASA Astrophysics Data System (ADS)

    Montgomery, M. M.

    2017-03-01

    In this work, we review the three most likely evolutionary channels that may result in AM CVn close binaries leading to white dwarf supernovae as evolutionary endpoints. To determine the likely evolutionary path for an AM CVn system, masses are needed. To find the secondary-to-primary mass ratio, a recent hypothesis suggests using the positive superhump period from Stage A of the superoutburst light curve rather than Stage B. To determine the most likely evolutionary track for this system, we compare observational data with values from three 3D SPH numerical simulations, one simulation for each of the potential evolutionary channels for AM CVn system SDSS J090221.35+38941.9. In this work, we explain why the white dwarf channel may be eliminated for this system. As for the other two channels, we find that the simulated parameters for the CV channel looks most promising for the primary white dwarf J0902 to reach supernova type Ia. However, a comparison of simulated and observed positive superhump period excess values suggests that the helium star channel is more likely, although the results do not support a supernova as the white dwarf primary's endpoint.

  17. Hyper X-ray Flares on Active Stars Detected with MAXI

    NASA Astrophysics Data System (ADS)

    Higa, Masaya; Tsuboi, Yohko; Negoro, Hitoshi; Nakahira, Satoshi; Tomida, Hiroshi; Matsuoka, Masaru; aff002

    2014-08-01

    MAXI started its operation in 2009 August. Owing to its unprecedentedly high sensitivity as an all-sky X-ray monitor and to its capability of real-time data transfer, we have detected 56 strong flares from twenty-one active stars (eleven RS CVn systems, one Algol system, seven dMe stars, one dKe star and one Young Stellar Object). These flares have large X-ray luminosity of 6 × 1030 -5 × 1033 ergs s-1 in the 2-20 keV band. The flares can be thought to be high ends among their own categories. During the flare from AT Mic on 2012 April 18th, one of the largest X-ray luminosities was recorded as a dMe star, 6 × 1032 ergs s-1 in the 2-20 keV band. It is larger than its bolometric luminosity by 4 times. The total energy emitted during the flare is 1036 ergs in the same band. Such total energy can be obtained on large flares from RS CVn system, but not on any other flares from dMe stars. In this proceeding, we report on the present situation in characteristics of hyper X-ray flares on each stellar categories.

  18. PTF1 J071912.13+485834.0: AN OUTBURSTING AM CVn SYSTEM DISCOVERED BY A SYNOPTIC SURVEY

    SciTech Connect

    Levitan, David; Prince, Thomas A.; Fulton, Benjamin J.; Shporer, Avi; Groot, Paul J.; Kulkarni, Shrinivas R.; Ofek, Eran O.; Kasliwal, Mansi M.; Quimby, Robert M.; Horesh, Assaf; Sesar, Branimir; Bloom, Joshua S.; Bradley Cenko, S.; Poznanski, Dovi; Law, Nicholas M.; Nugent, Peter E.; Sternberg, Assaf

    2011-10-01

    We present extensive photometric and spectroscopic observations of PTF1 J071912.13+485834.0, an outbursting AM CVn system discovered by the Palomar Transient Factory (PTF). AM CVn systems are stellar binaries with some of the smallest separations known and orbital periods ranging from 5 to 65 minutes. They are believed to be composed of a white dwarf accretor and a (semi-)degenerate He-rich donor and are considered to be the helium equivalents of cataclysmic variables (CVs). We have spectroscopically and photometrically identified an orbital period of 26.77 {+-} 0.02 minutes for PTF1 J071912.13+485834.0 and found a super-outburst recurrence time of greater than 65 days along with the presence of 'normal' outbursts-rarely seen in AM CVn systems but well known in super-outbursting CVs. We present a long-term light curve over two super-cycles as well as high-cadence photometry of both outburst and quiescent stages, both of which show clear variability. We also compare both the outburst and quiescent spectra of PTF1 J071912.13+485834.0 to other known AM CVn systems, and use the quiescent phase-resolved spectroscopy to determine the origin of the photometric variability. Finally, we draw parallels between the different subclasses of SU UMa-type CVs and outbursting AM CVn systems. We conclude by predicting that the PTF may more than double the number of outbursting AM CVn systems known, which would greatly increase our understanding of AM CVn systems.

  19. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children.

    PubMed

    Muñoz-Yáñez, C; Pérez-Morales, R; Moreno-Macías, H; Calleros-Rincón, E; Ballesteros, G; González, R A; Espinosa, J

    2016-01-01

    Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism.

  20. Polymorphisms FTO rs9939609, PPARG rs1801282 and ADIPOQ rs4632532 and rs182052 but not lifestyle are associated with obesity related-traits in Mexican children

    PubMed Central

    Muñoz-Yáñez, C; Pérez-Morales, R; Moreno-Macías, H; Calleros-Rincón, E; Ballesteros, G; González, R. A; Espinosa, J

    2016-01-01

    Abstract Concerning the genetic factors of obesity, no consistent association between populations has been reported, which may be due to the frequency of polymorphisms, the lifestyle of studied populations and its interaction with other factors. We studied a possible association of polymorphisms FTO rs9939609, PPARG rs1801282, and ADIPOQ rs4632532 and rs182052 with obesity phenotypes in 215 Mexican children. Glucose, triglycerides, cholesterol, HDL and LDL were measured. In addition, weight, height, waist circumference and triceps skin thickness were recorded. High-energy diets and sedentary behavior were evaluated with a validated questionnaire. In contrast with other reports, only FTO rs9939609 was associated with obesity related-traits, including BMI (p = 0.03), waist circumference (p = 0.02), triceps skinfold (p = 0.03) and waist/height ratio (p = 0.01), and also with cholesterol levels (p = 0.02) and LDL (p = 0.009). Lower levels of triglycerides (p=0.04) were related with presence of PPARG rs1801282, while ADIPOQ rs4632532 showed an effect on HDL (p = 0.03) levels. On the other hand, diet, physical activity and screen time were not related with obesity. In summary, only FTO rs9939609 was associated with obesity related-traits, while PPARG2 rs1801282 and ADIPOQ rs4632532 were involved in lipid metabolism. PMID:27560839

  1. R/S analysis of reaction time in Neuron Type Test for human activity in civil aviation

    NASA Astrophysics Data System (ADS)

    Zhang, Hong-Yan; Kang, Ming-Cui; Li, Jing-Qiang; Liu, Hai-Tao

    2017-03-01

    Human factors become the most serious problem leading to accidents of civil aviation, which stimulates the design and analysis of Neuron Type Test (NTT) system to explore the intrinsic properties and patterns behind the behaviors of professionals and students in civil aviation. In the experiment, normal practitioners' reaction time sequences, collected from NTT, exhibit log-normal distribution approximately. We apply the χ2 test to compute the goodness-of-fit by transforming the time sequence with Box-Cox transformation to cluster practitioners. The long-term correlation of different individual practitioner's time sequence is represented by the Hurst exponent via Rescaled Range Analysis, also named by Range/Standard deviation (R/S) Analysis. The different Hurst exponent suggests the existence of different collective behavior and different intrinsic patterns of human factors in civil aviation.

  2. Tat-Mediated Induction of miRs-34a & -138 Promotes Astrocytic Activation via Downregulation of SIRT1: Implications for Aging in HAND.

    PubMed

    Hu, Guoku; Liao, Ke; Yang, Lu; Pendyala, Gurudutt; Kook, Yeonhee; Fox, Howard S; Buch, Shilpa

    2017-02-24

    Astrocyte activation is a hallmark of HIV infection and aging in the CNS. In chronically infected HIV patients, prolonged activation of astrocytes has been linked to accelerated aging including but not limited to neurocognitive impairment and frailty. The current study addresses the role of HIV protein Tat in inducing a set of small noncoding microRNAs (miRNA) that play critical role in astrogliosis. In our efforts to link astrocyte activation as an indicator of aging, we assessed the brains of both wild type and HIV transgenic rats for the expression of glial fibrillary acidic protein (GFAP). As expected, in the WT animals we observed age-dependent increase in astrogliosis in the older animals compared to the younger group. Interestingly, compared to the young WT group, young HIV Tg rats exhibited higher levels of GFAP in this trend was also observed in the older HIV Tg rats compared to the older WT group. Based on the role of SIRT1 in aging and the regulation of SIRT1 by miRNAs-34a and -138, we next assessed the expression levels of these miRs in the brains of both the young an old WT and HIV Tg rats. While there were no significant differences in the young WT versus the HIV Tg rats, in the older HIV Tg rats there was a significant upregulation in the expression of miRs-34a & -138 in the brains. Furthermore, increased expression of miRs-34a & -138 in the older Tg rats, correlated with a concomitant decrease in their common anti-aging target protein SIRT1, in the brains of these animals. To delineate the mechanism of action we assessed the role of HIV-Tat (present in the Tg rats) in inducing miRs-34a & -138 in both the primary astrocytes and the astrocytoma cell line A172, thereby leading to posttranscriptional suppression of SIRT1 with a concomitant up regulation of NF-kB driven expression of GFAP.

  3. Navy Nuclear Aircraft Carrier (CVN) Homeporting at Mayport: Background and Issues for Congress

    DTIC Science & Technology

    2012-02-21

    This is a deferral at this time due to fiscal constraints.” The Navy’s five Atlantic Fleet CVNs are all homeported at Norfolk, VA. The Navy wants to...mitigating risks to the Navy’s Atlantic Fleet CVNs are worth the costs associated with moving a CVN to Mayport. Certain Members of Congress from...mitigating risks to the Navy’s Atlantic Fleet CVNs are questionable or uncertain, and that the funding needed to implement the proposal could achieve

  4. Effects of Microstructure on CVN Impact Toughness in Thermomechanically Processed High Strength Microalloyed Steel

    NASA Astrophysics Data System (ADS)

    Jia, Tao; Zhou, Yanlei; Jia, Xiaoxiao; Wang, Zhaodong

    2017-02-01

    Investigation on the correlation between microstructure and CVN impact toughness is of practical importance for the microstructure design of high strength microalloyed steels. In this work, three steels with characteristic microstructures were produced by cooling path control, i.e., steel A with granular bainite (GB), steel B with polygonal ferrite (PF) and martensite-austenite (M-A) constituent, and steel C with the mixture of bainitic ferrite (BF), acicular ferrite (AF), and M-A constituent. Under the same alloy composition and controlled rolling, similar ductile-to-brittle transition temperatures were obtained for the three steels. Steel A achieved the highest upper shelf energy (USE), while large variation of impact absorbed energy has been observed in the ductile-to-brittle transition region. With apparently large-sized PF and M-A constituent, steel B shows the lowest USE and delamination phenomenon in the ductile-to-brittle transition region. Steel C exhibits an extended upper shelf region, intermediate USE, and the fastest decrease of impact absorbed energy in the ductile-to-brittle transition region. The detailed CVN impact behavior is studied and then linked to the microstructural features.

  5. Mechanisms of HIV-1 subtype C resistance to GRFT, CV-N and SVN

    PubMed Central

    Alexandre, Kabamba B.; Moore, Penny L.; Nonyane, Molati; Gray, Elin S.; Ranchobe, Nthabeleng; Chakauya, Ereck; McMahon, James B.; O’Keefe, Barry R.; Chikwamba, Rachel; Morris, Lynn

    2013-01-01

    We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis of gp120 showed that most had deletions of 1 to 5 mannose-rich glycans. Glycosylation sites at positions 230, 234, 241, 289 located in the C2 region and 339, 392 and 448 in the C3-C4 region were affected. Furthermore, deletions and insertions of up to 5 amino acids in the V4 region were observed in 3 of the 4 isolates. These data suggest that loss of glycosylation sites on gp120 as well as rearrangement of glycans in V4 are mechanisms involved in HIV-1 subtype C escape from GRFT, CV-N and SVN. PMID:24074568

  6. A Designed “Nested” Dimer of Cyanovirin-N Increases Antiviral Activity

    PubMed Central

    Woodrum, Brian W.; Maxwell, Jason; Allen, Denysia M.; Wilson, Jennifer; Krumpe, Lauren R.H.; Bobkov, Andrey A.; Hill, R. Blake; Kibler, Karen V.; O’Keefe, Barry R.; Ghirlanda, Giovanna

    2016-01-01

    Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface of enveloped viruses. In the case of HIV, antiviral activity of CV-N is postulated to require multivalent interactions with envelope protein gp120, achieved through a pseudo-repeat of sequence that adopts two near-identical glycan-binding sites, and possibly involves a 3D-domain-swapped dimeric form of CV-N. Here, we present a covalent dimer of CV-N that increases the number of active glycan-binding sites, and we characterize its ability to recognize four glycans in solution. A CV-N variant was designed in which two native repeats were separated by the “nested” covalent insertion of two additional repeats of CV-N, resulting in four possible glycan-binding sites. The resulting Nested CV-N folds into a wild-type-like structure as assessed by circular dichroism and NMR spectroscopy, and displays high thermal stability with a Tm of 59 °C, identical to WT. All four glycan-binding domains encompassed by the sequence are functional as demonstrated by isothermal titration calorimetry, which revealed two sets of binding events to dimannose with dissociation constants Kd of 25 μM and 900 μM, assigned to domains B and B’ and domains A and A’ respectively. Nested CV-N displays a slight increase in activity when compared to WT CV-N in both an anti-HIV cellular assay and a fusion assay. This construct conserves the original binding specifityies of domain A and B, thus indicating correct fold of the two CV-N repeats. Thus, rational design can be used to increase multivalency in antiviral lectins in a controlled manner. PMID:27275831

  7. A Designed "Nested" Dimer of Cyanovirin-N Increases Antiviral Activity.

    PubMed

    Woodrum, Brian W; Maxwell, Jason; Allen, Denysia M; Wilson, Jennifer; Krumpe, Lauren R H; Bobkov, Andrey A; Hill, R Blake; Kibler, Karen V; O'Keefe, Barry R; Ghirlanda, Giovanna

    2016-06-06

    Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface of enveloped viruses. In the case of HIV, antiviral activity of CV-N is postulated to require multivalent interactions with envelope protein gp120, achieved through a pseudo-repeat of sequence that adopts two near-identical glycan-binding sites, and possibly involves a 3D-domain-swapped dimeric form of CV-N. Here, we present a covalent dimer of CV-N that increases the number of active glycan-binding sites, and we characterize its ability to recognize four glycans in solution. A CV-N variant was designed in which two native repeats were separated by the "nested" covalent insertion of two additional repeats of CV-N, resulting in four possible glycan-binding sites. The resulting Nested CV-N folds into a wild-type-like structure as assessed by circular dichroism and NMR spectroscopy, and displays high thermal stability with a Tm of 59 °C, identical to WT. All four glycan-binding domains encompassed by the sequence are functional as demonstrated by isothermal titration calorimetry, which revealed two sets of binding events to dimannose with dissociation constants Kd of 25 μM and 900 μM, assigned to domains B and B' and domains A and A' respectively. Nested CV-N displays a slight increase in activity when compared to WT CV-N in both an anti-HIV cellular assay and a fusion assay. This construct conserves the original binding specifityies of domain A and B, thus indicating correct fold of the two CV-N repeats. Thus, rational design can be used to increase multivalency in antiviral lectins in a controlled manner.

  8. Superoutburst of CR Bootis: Estimation of mass ratio of a typical AM CVn star by stage A superhumps

    NASA Astrophysics Data System (ADS)

    Isogai, Keisuke; Kato, Taichi; Ohshima, Tomohito; Kasai, Kiyoshi; Oksanen, Arto; Masumoto, Kazunari; Fukushima, Daiki; Maeda, Kazuki; Kawabata, Miho; Matsuda, Risa; Kojiguchi, Naoto; Sugiura, Yuki; Takeda, Nao; Matsumoto, Katsura; Itoh, Hiroshi; Pavlenko, Elena P.; Antonyuk, Kirill; Antonyuk, Oksana; Pit, Nikolai; Sosnovskij, Aleksei; Baklanov, Alex; Babina, Julia; Sklyanov, Aleksandr; Kiyota, Seiichiro; Hambsch, Franz-Josef; Littlefield, Colin; Maeda, Yutaka; Cook, Lewis M.; Masi, Gianluca; Dubovsky, Pavol A.; Novák, Rudolf; Dvorak, Shawn; Imada, Akira; Nogami, Daisaku

    2016-08-01

    We report on two superoutbursts of the AM CVn-type object CR Boo in 2014 April-March and 2015 May-June. A precursor outburst accompanied both of these superoutbursts. During the rising branch of the main superoutburst in 2014, we detected growing superhumps (stage A superhumps) whose period was 0.017669(24) d. Assuming that this period reflects the dynamical precession rate at the radius of the 3:1 resonance, we could estimate the mass ratio (q = M2/M1) of 0.101(4) by using the stage A superhump period and the orbital period of 0.0170290(6) d. This mass ratio is consistent with that expected from the theoretical evolutionary model of AM CVn-type objects. The detection of precursor outbursts and stage A superhumps is the second case in AM CVn-type objects. There are two interpretations of the outbursts of AM CVn-type objects. One is a dwarf nova (DN) outbursts analogy, which suggets that the outbursts are caused by thermal and tidal instabilities. Another is the VY Scl-type variation, which suggests that the outbursts are caused by the variation of the mass-transfer rate of the secondary.This detection of the superhump variations strongly supports the former interpretation.

  9. The A Allele of the Single-Nucleotide Polymorphism rs630923 Creates a Binding Site for MEF2C Resulting in Reduced CXCR5 Promoter Activity in B-Cell Lymphoblastic Cell Lines.

    PubMed

    Mitkin, Nikita A; Muratova, Alisa M; Schwartz, Anton M; Kuprash, Dmitry V

    2016-01-01

    Chemokine receptor CXCR5 is highly expressed in B-cells and under normal conditions is involved in their migration to specific areas of secondary lymphoid organs. B-cells are known to play an important role in various autoimmune diseases including multiple sclerosis (MS) where areas of demyelinating lesions attract B-cells by overexpressing CXCL13, the CXCR5 ligand. In this study, we aimed to determine the functional significance of single-nucleotide polymorphism rs630923 (A/C), which is located in cxcr5 gene promoter, and its common allele is associated with increased risk of MS. Using bioinformatics and pull-down assay in B-lymphoblastic cell lines, we showed that protective minor rs630923 "A" allele created functional binding site for MEF2C transcription factor. Elevated MEF2C expression in B-cells correlated with reduced activity of cxcr5 promoter containing rs630923 "A" allele. This effect that was fully neutralized by MEF2C-directed siRNA may mechanistically explain the protective role of the rs630923 minor allele in MS. Using site-directed mutagenesis of the cxcr5 gene promoter, we were unable to find any experimental evidence for the previously proposed role of NFκB transcription factors in rs630923-mediated CXCR5 promoter regulation. Thus, our results identify MEF2C as a possible mediator of protective function of the rs630923 "A" allele in MS.

  10. The active chromosphere binary HD 17433 (VY Arietis)

    NASA Technical Reports Server (NTRS)

    Bopp, Bernard W.; Dempsey, Robert; Saar, Steven H.; Ambruster, Carol; Feldman, Paul

    1989-01-01

    The sixth-magnitude K star HD 17433 (VY Ari) is shown to be an active-chromosphere binary with an orbital period of 13.198 days. A photometric (rotational) period of 17.4 days is indicated by the existing photometry, implying that HD 17433 is not in synchronous rotation. In the optical, H-alpha is seen in emission, with variable profile and intensity; He I lambda-5876 is present in absorption. IUE observations show chromospheric and transition-region emission lines with surface fluxes up to 200 times greater than those observed in the quiet sun. The luminosity and radius are appropriate for a subgiant, and the kinematics suggest Pleiades group membership. The presence of a lithium absorption feature indicates it may either be a young object, possibly a pre-main sequence star or an evolved spotted RS CVn system. Interpretations from the optical measurement of the magnetic field strength of HD 17433 are given.

  11. Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs.

    PubMed

    Murthy, Vidya; Taranda, Julián; Elgoyhen, A Belén; Vetter, Douglas E

    2009-12-01

    Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) alpha9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR alpha9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in alpha9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the alpha9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult alpha9 null mice. Finally, by using mice expressing the nondesensitizing alpha9 L9'T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation.

  12. [MaRS Project

    NASA Technical Reports Server (NTRS)

    Aruljothi, Arunvenkatesh

    2016-01-01

    The Space Exploration Division of the Safety and Mission Assurances Directorate is responsible for reducing the risk to Human Space Flight Programs by providing system safety, reliability, and risk analysis. The Risk & Reliability Analysis branch plays a part in this by utilizing Probabilistic Risk Assessment (PRA) and Reliability and Maintainability (R&M) tools to identify possible types of failure and effective solutions. A continuous effort of this branch is MaRS, or Mass and Reliability System, a tool that was the focus of this internship. Future long duration space missions will have to find a balance between the mass and reliability of their spare parts. They will be unable take spares of everything and will have to determine what is most likely to require maintenance and spares. Currently there is no database that combines mass and reliability data of low level space-grade components. MaRS aims to be the first database to do this. The data in MaRS will be based on the hardware flown on the International Space Stations (ISS). The components on the ISS have a long history and are well documented, making them the perfect source. Currently, MaRS is a functioning excel workbook database; the backend is complete and only requires optimization. MaRS has been populated with all the assemblies and their components that are used on the ISS; the failures of these components are updated regularly. This project was a continuation on the efforts of previous intern groups. Once complete, R&M engineers working on future space flight missions will be able to quickly access failure and mass data on assemblies and components, allowing them to make important decisions and tradeoffs.

  13. Acid-Induced Activation of the Urease Promoters Is Mediated Directly by the ArsRS Two-Component System of Helicobacter pylori

    PubMed Central

    Pflock, Michael; Kennard, Simone; Delany, Isabel; Scarlato, Vincenzo; Beier, Dagmar

    2005-01-01

    The nickel-containing enzyme urease is an essential colonization factor of the human gastric pathogen Helicobacter pylori which enables the bacteria to survive the low-pH conditions of the stomach. Transcription of the urease genes is positively controlled in response to increasing concentrations of nickel ions and acidic pH. Here we demonstrate that acid-induced transcription of the urease genes is mediated directly by the ArsRS two-component system. Footprint analyses identify binding sites of the phosphorylated ArsR response regulator within the ureA and ureI promoters. Furthermore, deletion of a distal upstream ArsR binding site of the ureA promoter demonstrates its role in acid-dependent activation of the promoter. In addition, acid-induced transcription of the ureA gene is unaltered in a nikR mutant, providing evidence that pH-responsive regulation and nickel-responsive regulation of the ureA promoter are mediated by independent mechanisms involving the ArsR response regulator and the NikR protein. PMID:16177315

  14. Potential anticancer activity of carvone in N2a neuroblastoma cell line.

    PubMed

    Aydın, Elanur; Türkez, Hasan; Keleş, Mevlüt Sait

    2015-08-01

    Carvone (CVN) is a monocyclic monoterpene found in the essential oils of Mentha spicata var. crispa (Lamiaceae) and Carum carvi L. (Apiaceae) plants and has been reported to have antioxidant, antimicrobial, anticonvulsant, and antitumor activities. The beneficial health properties of CVN have encouraged us to look into its anticancer activity. To the best of our knowledge, reports are not available on the anticancer activity of CVN in cultured primary rat neuron and N2a neuroblastoma (NB) cells. Therefore, the present study is an attempt toward exploring the potential anticancer activity of CVN, if any, in cultured primary rat neuron and N2a NB cells. Our results indicated that CVN (only at 25 mg/L) treatment led to an increase in the total antioxidant capacity levels in cultured primary rat neuron cells compared with control cells. Also, CVN (at concentrations higher than 100 mg/L) treatment led to an increase in the total oxidative stress levels in both cell types. The mean values of the total scores of cells showing DNA damage (for comet assay) were not found to be significantly different from the control values in both cells (p > 0.05). On the other hand, after 24 h treatment with CVN, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay showed that CVN application significantly reduced the cell viability rates in both cell types at concentrations higher than 100 mg/L. Summarizing, our data suggest that CVN represents little potential for promising anticancer agent to improve brain tumors therapy.

  15. The Crohn's disease-associated polymorphism in ATG16L1 (rs2241880) reduces SHIP gene expression and activity in human subjects.

    PubMed

    Ngoh, E N; Brugger, H K; Monajemi, M; Menzies, S C; Hirschfeld, A F; Del Bel, K L; Jacobson, K; Lavoie, P M; Turvey, S E; Sly, L M

    2015-10-01

    Crohn's disease (CD) is a polygenic immune-mediated disease characterized by gastrointestinal inflammation. Mice deficient in the hematopoietic-restricted SH2 domain-containing inositolpolyphosphate 5'-phosphatase (SHIP) develop spontaneous CD-like ileal inflammation. Intriguingly, SHIP mRNA is not upregulated in biopsies from patients with ileal CD despite immune cell infiltration, but SHIP's role in human CD remains unknown. We analyzed SHIP mRNA expression and activity in biopsies and peripheral blood mononuclear cells (PBMCs) from control and treatment-naive subjects with ileal CD, and demonstrated that SHIP mRNA and activity were lower in hematopoietic cells in ileal biopsies and PBMCs from subjects with CD. In all tissues from our patient cohort and in PBMCs from a second healthy control cohort, subjects homozygous for the autophagy-related 16-like protein (ATG16L1) CD-associated gene variant (rs2241880), had low SHIP mRNA expression and activity. SHIP protein expression increased during autophagy and SHIP upregulation was dependent on ATG16L1 and/or autophagy, as well as the ATG16L1 CD-associated gene variant. Finally, homozygosity for the ATG16L1 risk variant and low SHIP mRNA expression is inversely related to increased (LPS+ATP)-induced IL-1β production by PBMCs in our cohorts and was regulated by increased transcription of ILIB. These data suggest a novel mechanism by which the ATG16L1 CD-associated gene variant may predispose people to develop intestinal inflammation.

  16. A Close Association of RyRs with Highly Dense Clusters of Ca2+-activated Cl− Channels Underlies the Activation of STICs by Ca2+ Sparks in Mouse Airway Smooth Muscle

    PubMed Central

    Bao, Rongfeng; Lifshitz, Lawrence M.; Tuft, Richard A.; Bellvé, Karl; Fogarty, Kevin E.; ZhuGe, Ronghua

    2008-01-01

    Ca2+ sparks are highly localized, transient releases of Ca2+ from sarcoplasmic reticulum through ryanodine receptors (RyRs). In smooth muscle, Ca2+ sparks trigger spontaneous transient outward currents (STOCs) by opening nearby clusters of large-conductance Ca2+-activated K+ channels, and also gate Ca2+-activated Cl− (Cl(Ca)) channels to induce spontaneous transient inward currents (STICs). While the molecular mechanisms underlying the activation of STOCs by Ca2+ sparks is well understood, little information is available on how Ca2+ sparks activate STICs. In the present study, we investigated the spatial organization of RyRs and Cl(Ca) channels in spark sites in airway myocytes from mouse. Ca2+ sparks and STICs were simultaneously recorded, respectively, with high-speed, widefield digital microscopy and whole-cell patch-clamp. An image-based approach was applied to measure the Ca2+ current underlying a Ca2+ spark (ICa(spark)), with an appropriate correction for endogenous fixed Ca2+ buffer, which was characterized by flash photolysis of NPEGTA. We found that ICa(spark) rises to a peak in 9 ms and decays with a single exponential with a time constant of 12 ms, suggesting that Ca2+ sparks result from the nonsimultaneous opening and closure of multiple RyRs. The onset of the STIC lags the onset of the ICa(spark) by less than 3 ms, and its rising phase matches the duration of the ICa(spark). We further determined that Cl(Ca) channels on average are exposed to a [Ca2+] of 2.4 μM or greater during Ca2+ sparks. The area of the plasma membrane reaching this level is <600 nm in radius, as revealed by the spatiotemporal profile of [Ca2+] produced by a reaction-diffusion simulation with measured ICa(spark). Finally we estimated that the number of Cl(Ca) channels localized in Ca2+ spark sites could account for all the Cl(Ca) channels in the entire cell. Taken together these results lead us to propose a model in which RyRs and Cl(Ca) channels in Ca2+ spark sites localize

  17. RS-84 Engine

    NASA Technical Reports Server (NTRS)

    Stegman, E.

    2003-01-01

    The RS-84 is the first reusable hydrocarbon staged combustion liquid rocket engine. This engine is being developed to meet NASA s crew safety goals with a highly reliable and low cost main engine as a part of the NASA Space Launch Initiative program for the next generation reusable launch system. The NASA-MSFC and Rocketdyne team brings over 50 years of successful rocket engine development experience to meet the challenges of this new program. This team s extensive design database has been anchored with almost five decades of hydrocarbon rocket engine development and flight operations experience including Delta, Atlas, and Saturn vehicles and nearly three decades of successfully operating the world s only reusable pump-fed rocket engine, the Space Shuttle Main Engine. The team also fully benefits from the proven and experienced engineering staffs that recently completed the successful MC-1 FASTRAC , XRS-2200, and RS-68 engine development programs and the ongoing IPD and RS-76 technology development. Advances in integrated parametric design and analysis tools, advanced materials knowledge base, and state-of-the-art fabrication processes anchored and refined during the recent engine development programs are already being used by the team to design this engine.

  18. Anticancer activity and cDNA microarray studies of a (RS)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine, and an acyclic (RS)-O,N-acetalic 6-chloro-7H-purine.

    PubMed

    Caba, Octavio; Díaz-Gavilán, Mónica; Rodríguez-Serrano, Fernando; Boulaiz, Houria; Aránega, Antonia; Gallo, Miguel A; Marchal, Juan A; Campos, Joaquín M

    2011-09-01

    Completing a SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines was previously prepared. The most potent antiproliferative agent against the MCF-7 adenocarcinoma cell line that belongs to the benzoxazepine O,N-acetalic family is (RS)-9-[1-(9H-fluorenyl-9-methoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine (16, IC(50) = 0.67 ± 0.18 μM), whilst (RS)-7-{2-(N-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-6-chloro-7H-purine (37) shows the lowest IC(50) value between the family of acyclic O,N-acetals (IC(50) = 3.25 ± 0.23 μM). Moreover, 16 showed the better in vitro Therapeutic Index in breast cell lines (3.19), whilst 37 was found to be 3.69-fold more active against HT-29 human colon cancer cell line than versus IEC-6 normal rat intestinal epithelial cell line. The global apoptotic cells caused by 16 and 37 against MCF-7 were 80.08% and 54.85% of cell population after 48 h, respectively. cDNA microarray technology reveals potential drug targets, which are mainly centred on positive apoptosis regulatory pathway genes, and the repression of genes involved in carcinogenesis, proliferation and tumour invasion.

  19. [Activities of Space Telescope Science Institute with the Hubble Space Telescope

    NASA Technical Reports Server (NTRS)

    Dempsey, Robert C.; Neff, James E.; Strassmeier, Klaus G.; Linsky, Jeffrey L.

    1998-01-01

    A number of studies, especially in recent years with the Hubble Space Telescope's (HST) Goddard High Resolution Spectrograph (GHRS), have been presented on the UV line profiles of late-type stars. Generally, these consist of a few "snapshot" spectra of several different key diagnostic emission lines. From this it has become clear that many active stars possess non-gaussian line profiles. Unlike the case with AR Lac, observed with IUE, no assymetric profile has been clearly identified that results from an inhomogeneous surface temperature or density distribution. In 1993 we attempted to observe the RS CVn binary V711 Tau at several phases with the GHRS in a number of UV bandpasses in order to study profile variations as a function of phase. Unfortunately, scheduling problems, pointing errors, continuous flaring and the sparse and uneven phase sampling prevented us from achieving the primary goal. However, it is clear that a number of UV lines in the system, notably C IV, Si IV and Mg II show very extended emission out to several hundred km/s. The profiles were also clearly variable. Vilhu et al. (1997) and Walter et al. (1995) conducted a campaign on the rapidly rotating, single star AB Dor, where they observed C IV continuously for 14 hours. They found extended, non-gaussian emission in the C IV doublet and that Doppler images derived from these images were remarkably similar to the simultaneous spot-image. In a follow up study of V711 Tau we have observed another RS CVn with complete phase coverage in three key wavelength bandpasses, utilizing the ability of HST to observe some stars at high latitudes in uninterrupted fashion. Generally classified as an RS CVn, V824 Ara (HD 155555) consists of a G5 IV star in a short period orbit (P=ld.68) with a K0 V-IV companion. However, the system does not eclipse and therefore does not rigorously fit the Hall (1976) definition. There is also a visual M star companion (LDS587B) 33 arcsec away. The space velocities of the stars

  20. FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.

    PubMed

    Peterlongo, Paolo; Catucci, Irene; Colombo, Mara; Caleca, Laura; Mucaki, Eliseos; Bogliolo, Massimo; Marin, Maria; Damiola, Francesca; Bernard, Loris; Pensotti, Valeria; Volorio, Sara; Dall'Olio, Valentina; Meindl, Alfons; Bartram, Claus; Sutter, Christian; Surowy, Harald; Sornin, Valérie; Dondon, Marie-Gabrielle; Eon-Marchais, Séverine; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Sinilnikova, Olga M; Mitchell, Gillian; James, Paul A; Thompson, Ella; Marchetti, Marina; Verzeroli, Cristina; Tartari, Carmen; Capone, Gabriele Lorenzo; Putignano, Anna Laura; Genuardi, Maurizio; Medici, Veronica; Marchi, Isabella; Federico, Massimo; Tognazzo, Silvia; Matricardi, Laura; Agata, Simona; Dolcetti, Riccardo; Della Puppa, Lara; Cini, Giulia; Gismondi, Viviana; Viassolo, Valeria; Perfumo, Chiara; Mencarelli, Maria Antonietta; Baldassarri, Margherita; Peissel, Bernard; Roversi, Gaia; Silvestri, Valentina; Rizzolo, Piera; Spina, Francesca; Vivanet, Caterina; Tibiletti, Maria Grazia; Caligo, Maria Adelaide; Gambino, Gaetana; Tommasi, Stefania; Pilato, Brunella; Tondini, Carlo; Corna, Chiara; Bonanni, Bernardo; Barile, Monica; Osorio, Ana; Benitez, Javier; Balestrino, Luisa; Ottini, Laura; Manoukian, Siranoush; Pierotti, Marco A; Renieri, Alessandra; Varesco, Liliana; Couch, Fergus J; Wang, Xianshu; Devilee, Peter; Hilbers, Florentine S; van Asperen, Christi J; Viel, Alessandra; Montagna, Marco; Cortesi, Laura; Diez, Orland; Balmaña, Judith; Hauke, Jan; Schmutzler, Rita K; Papi, Laura; Pujana, Miguel Angel; Lázaro, Conxi; Falanga, Anna; Offit, Kenneth; Vijai, Joseph; Campbell, Ian; Burwinkel, Barbara; Kvist, Anders; Ehrencrona, Hans; Mazoyer, Sylvie; Pizzamiglio, Sara; Verderio, Paolo; Surralles, Jordi; Rogan, Peter K; Radice, Paolo

    2015-09-15

    Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.

  1. FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor

    PubMed Central

    Peterlongo, Paolo; Catucci, Irene; Colombo, Mara; Caleca, Laura; Mucaki, Eliseos; Bogliolo, Massimo; Marin, Maria; Damiola, Francesca; Bernard, Loris; Pensotti, Valeria; Volorio, Sara; Dall'Olio, Valentina; Meindl, Alfons; Bartram, Claus; Sutter, Christian; Surowy, Harald; Sornin, Valérie; Dondon, Marie-Gabrielle; Eon-Marchais, Séverine; Stoppa-Lyonnet, Dominique; Andrieu, Nadine; Sinilnikova, Olga M.; Mitchell, Gillian; James, Paul A.; Thompson, Ella; Marchetti, Marina; Verzeroli, Cristina; Tartari, Carmen; Capone, Gabriele Lorenzo; Putignano, Anna Laura; Genuardi, Maurizio; Medici, Veronica; Marchi, Isabella; Federico, Massimo; Tognazzo, Silvia; Matricardi, Laura; Agata, Simona; Dolcetti, Riccardo; Puppa, Lara Della; Cini, Giulia; Gismondi, Viviana; Viassolo, Valeria; Perfumo, Chiara; Mencarelli, Maria Antonietta; Baldassarri, Margherita; Peissel, Bernard; Roversi, Gaia; Silvestri, Valentina; Rizzolo, Piera; Spina, Francesca; Vivanet, Caterina; Tibiletti, Maria Grazia; Caligo, Maria Adelaide; Gambino, Gaetana; Tommasi, Stefania; Pilato, Brunella; Tondini, Carlo; Corna, Chiara; Bonanni, Bernardo; Barile, Monica; Osorio, Ana; Benitez, Javier; Balestrino, Luisa; Ottini, Laura; Manoukian, Siranoush; Pierotti, Marco A.; Renieri, Alessandra; Varesco, Liliana; Couch, Fergus J.; Wang, Xianshu; Devilee, Peter; Hilbers, Florentine S.; van Asperen, Christi J.; Viel, Alessandra; Montagna, Marco; Cortesi, Laura; Diez, Orland; Balmaña, Judith; Hauke, Jan; Schmutzler, Rita K.; Papi, Laura; Pujana, Miguel Angel; Lázaro, Conxi; Falanga, Anna; Offit, Kenneth; Vijai, Joseph; Campbell, Ian; Burwinkel, Barbara; Kvist, Anders; Ehrencrona, Hans; Mazoyer, Sylvie; Pizzamiglio, Sara; Verderio, Paolo; Surralles, Jordi; Rogan, Peter K.; Radice, Paolo

    2015-01-01

    Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28–12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04–12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09–13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer. PMID:26130695

  2. Flavonoids from the grains of C1/R-S transgenic rice, the transgenic Oryza sativa spp. japonica, and their radical scavenging activities.

    PubMed

    Cho, Jin-Gyeong; Song, Na-Young; Nam, Tae-Gyu; Shrestha, Sabina; Park, Hee-Jung; Lyu, Ha-Na; Kim, Dae-Ok; Lee, Gihwan; Woo, Young-Min; Jeong, Tae-Sook; Baek, Nam-In

    2013-10-30

    The transgenic rice cultivar of Oryza sativa spp. japonica cv. Hwa-Young, C1/R-S transgenic rice (C1/R-S rice), is a flavonoid-rich cultivar of rice. The grains of C1/R-S rice were extracted with aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH, and H2O, successively. Repeated silica gel, octadecyl silica gel (ODS), and Sephadex LH-20 column chromatographies for the EtOAc and n-BuOH fractions afforded four new flavonoids (compounds 2, 3, 7, and 8) along with four known flavonoids: (+)-3'-O-methyltaxifolin (1), brassicin (4), isorhamnetin-4'-O-β-D-glucosyranoside (5), and 3'-O-methyltaxifolin-5-O-β-D-glucopyranoside (6). The new flavonoids were identified as 3'-O-methyltaxifolin-7-O-β-D-glucopyranoside (2), 3'-O-methyltaxifolin-4'-O-β-D-glucopyranoside (3), isorhamnetin-7-O-β-D-cellobioside (brassicin-4″-O-β-D-glucopyranoside) (7), and brassicin-4'-O-β-D-glucosyranoside (8) from the result of spectroscopic data including nuclear magnetic resonance spectrometry (NMR), mass spectrometry (MS), and infrared spectroscopy (IR). Also, quantitative analysis of major flavonoids (compounds 2, 3, and 8) in C1/R-S rice, O. sativa spp. japonica cv. Hwa-Young (HY), and a hybrid of two cultivar (C1/R-S rice/HY) extracts was performed using HPLC experiment. The isolated flavonoids were evaluated for their radical-scavenging effect on DPPH and ABTS radicals.

  3. Characterization of RsMYB28 and RsMYB29 transcription factor genes in radish (Raphanus sativus L.).

    PubMed

    Luo, X B; Liu, Z; Xu, L; Wang, Y; Zhu, X W; Zhang, W; Chen, W; Zhu, Y L; Su, X J; Everlyne, M; Liu, L W

    2016-09-23

    Glucosinolates (GSLs) are important secondary metabolites in Brassicaceae plants. Previous studies have mainly focused on GSL contents, types, and biosynthesis-related genes, but the molecular characterization patterns of GSL biosynthesis-related transcription factors remain largely unexplored in radish (Raphanus sativus L.). To isolate transcription factor genes regulating the GSL biosynthesis, genomic DNA and cDNA sequences of RsMYB28 and RsMYB29 genes were isolated in radish. Two R2R3-MYB domains were identified in the deduced amino acid sequences. Subcellular localization and yeast-one hybrid assays indicated that both the RsMYB28 and RsMYB29 genes were located in the nucleus and possessed transactivation activity. Reverse transcription quantitative analysis showed that the RsMYB28 and RsMYB29 genes were expressed in seeds, leaves, stems, and roots at the seedling, taproot thickening, and mature stages. Both genes were highly expressed during the seedling and taproot thickening stages. The expression level of RsMYB28 was found to be up-regulated following wounding, glucose, and abscisic acid treatments, whereas RsMYB29 was up-regulated following wounding and methyl jasmonate treatments. These results provide insights into the biological function and characterization of the RsMYB28 and RsMYB29 genes, and facilitate further dissection of the molecular regulatory mechanism underlying the GSL biosynthesis in radish.

  4. Carrier Landing Parameters from Survey 45, Fleet and Training Command Aircraft Landing Aboard USS ENTERPRISE CVN-65 (Appendices B Through R)

    DTIC Science & Technology

    1991-12-01

    nu B-3 NADC-91124-0 MODEL F-14A AIRCRAFT USS ENTERPRISE (CVN-65) DAY LANDINGS FRESNEL LENS SETTING-3.50 DEGREES (.061 RADIANS) N-158 X-27.85 KNOTS...ENTERPRISE (CVN-65) DAY LANDINGS FRESNEL LENS SETTING-3.50 DEGREES (.061 RADIANS) N-158 1-27.85 KNOTS (14.32 METRES/SEC) A3-.38 S-3.39 KNOTS (1.74 XETRES...AIRCRAFT USS ENTERPRISE (CVN-65) DAY LANDINGS FRESNEL LENS SETTING-3.50 DEGREES (.061 RADIANS) N-158 1-140.43 KNOTS (72.24 METRES/SEC) A3--.01 8-4.03 KNOTS

  5. The radish defensins RsAFP1 and RsAFP2 act synergistically with caspofungin against Candida albicans biofilms.

    PubMed

    Vriens, Kim; Cools, Tanne L; Harvey, Peta J; Craik, David J; Braem, Annabel; Vleugels, Jozef; De Coninck, Barbara; Cammue, Bruno P A; Thevissen, Karin

    2016-01-01

    The radish defensin RsAFP2 was previously characterized as a peptide with potent antifungal activity against several plant pathogenic fungi and human pathogens, including Candida albicans. RsAFP2 induces apoptosis and impairs the yeast-to-hypha transition in C. albicans. As the yeast-to-hypha transition is considered important for progression to mature biofilms, we analyzed the potential antibiofilm activity of recombinant (r)RsAFP2, heterologously expressed in Pichia pastoris, against C. albicans biofilms. We found that rRsAFP2 prevents C. albicans biofilm formation with a BIC-2 (i.e., the minimal rRsAFP2 concentration that inhibits biofilm formation by 50% as compared to control treatment) of 1.65 ± 0.40 mg/mL. Moreover, biofilm-specific synergistic effects were observed between rRsAFP2 doses as low as 2.5 μg/mL to 10 μg/mL and the antimycotics caspofungin and amphotericin B, pointing to the potential of RsAFP2 as a novel antibiofilm compound. In addition, we characterized the solution structure of rRsAFP2 and compared it to that of RsAFP1, another defensin present in radish seeds. These peptides have similar amino acid sequences, except for two amino acids, but rRsAFP2 is more potent than RsAFP1 against planktonic and biofilm cultures. Interestingly, as in case of rRsAFP2, also RsAFP1 acts synergistically with caspofungin against C. albicans biofilms in a comparable low dose range as rRsAFP2. A structural comparison of both defensins via NMR analysis revealed that also rRsAFP2 adopts the typical cysteine-stabilized αβ-motif of plant defensins, however, no structural differences were found between these peptides that might result in their differential antifungal/antibiofilm potency. This further suggests that the conserved structure of RsAFP1 and rRsAFP2 bears the potential to synergize with antimycotics against C. albicans biofilms.

  6. Whole transcriptome profiling of the human hippocampus suggests an involvement of the KIBRA rs17070145 polymorphism in differential activation of the MAPK signaling pathway.

    PubMed

    Piras, I S; Krate, J; Schrauwen, I; Corneveaux, J J; Serrano, G E; Sue, L; Beach, T G; Huentelman, M J

    2017-04-05

    The rs17070145-T variant of the WWC1 gene, coding for the KIBRA protein, has been associated with both increased episodic memory performance and lowered risk for late onset Alzheimer's disease, although the mechanism behind this protective effect has not been completely elucidated. To achieve a better understanding of the pathways modulated by rs17070145 and its associated functional variant(s), we used laser capture microdissection (LCM) and RNA-sequencing to investigate the effect of rs17070145 genotypes on whole transcriptome expression in the human hippocampus (HP) of 22 neuropathologically normal individuals, with a specific focus on the dentate gyrus (DG) and at the pyramidal cells (PC) of CA1 and CA3 sub-regions. Differential expression analysis of RNA-seq data within the HP based on the rs17070145 genotype revealed an overexpression of genes involved in the MAPK signaling pathway, potentially driven by the T/T genotype. The most important contribution comes from genes dysregulated within the DG region. Other genes significantly dysregulated, and not involved in the MAPK1 pathway (Adj P < 0.01 and Fold Change > |1.00|) were: RSPO4 (HP); ARC, DUSP5, DNAJB5, EGR4, PPP1R15A, WBP11P1, EGR1, GADD45B (DG); CH25H, HSPA1A, HSPA1B, TNFSF9 and NPAS4 (PC). Several evidences suggested that the MAPK signaling pathway is linked with memory and learning processes. In non-neuronal cells, the KIBRA protein is phosphorylated by ERK1/2 (involved in the MAPK signaling) in cells as well as in vitro. Several of the other dysregulated genes are involved in memory and learning processes, as well as in Alzheimer's Disease. In conclusion, our results suggest that the effect of the WWC1 rs17070145 polymorphism on memory performance and Alzheimer's disease might be due to a differential regulation of the MAPK signaling, a key pathway involved in memory and learning processes. This article is protected by copyright. All rights reserved.

  7. Crosstalk between the HpArsRS two-component system and HpNikR is necessary for maximal activation of urease transcription

    PubMed Central

    Carpenter, Beth M.; West, Abby L.; Gancz, Hanan; Servetas, Stephanie L.; Pich, Oscar Q.; Gilbreath, Jeremy J.; Hallinger, Daniel R.; Forsyth, Mark H.; Merrell, D. Scott; Michel, Sarah L. J.

    2015-01-01

    Helicobacter pylori NikR (HpNikR) is a nickel dependent transcription factor that directly regulates a number of genes in this important gastric pathogen. One key gene that is regulated by HpNikR is ureA, which encodes for the urease enzyme. In vitro DNA binding studies of HpNikR with the ureA promoter (PureA) previously identified a recognition site that is required for high affinity protein/DNA binding. As a means to determine the in vivo significance of this recognition site and to identify the key DNA sequence determinants required for ureA transcription, herein, we have translated these in vitro results to analysis directly within H. pylori. Using a series of GFP reporter constructs in which the PureA DNA target was altered, in combination with mutant H. pylori strains deficient in key regulatory proteins, we confirmed the importance of the previously identified HpNikR recognition sequence for HpNikR-dependent ureA transcription. Moreover, we identified a second factor, the HpArsRS two-component system that was required for maximum transcription of ureA. While HpArsRS is known to regulate ureA in response to acid shock, it was previously thought to function independently of HpNikR and to have no role at neutral pH. However, our qPCR analysis of ureA expression in wildtype, ΔnikR and ΔarsS single mutants as well as a ΔarsS/nikR double mutant strain background showed reduced basal level expression of ureA when arsS was absent. Additionally, we determined that both HpNikR and HpArsRS were necessary for maximal expression of ureA under nickel, low pH and combined nickel and low pH stresses. In vitro studies of HpArsR-P with the PureA DNA target using florescence anisotropy confirmed a direct protein/DNA binding interaction. Together, these data support a model in which HpArsRS and HpNikR cooperatively interact to regulate ureA transcription under various environmental conditions. This is the first time that direct “cross-talk” between HpArsRS and HpNikR at

  8. Crosstalk between the HpArsRS two-component system and HpNikR is necessary for maximal activation of urease transcription.

    PubMed

    Carpenter, Beth M; West, Abby L; Gancz, Hanan; Servetas, Stephanie L; Pich, Oscar Q; Gilbreath, Jeremy J; Hallinger, Daniel R; Forsyth, Mark H; Merrell, D Scott; Michel, Sarah L J

    2015-01-01

    Helicobacter pylori NikR (HpNikR) is a nickel dependent transcription factor that directly regulates a number of genes in this important gastric pathogen. One key gene that is regulated by HpNikR is ureA, which encodes for the urease enzyme. In vitro DNA binding studies of HpNikR with the ureA promoter (PureA ) previously identified a recognition site that is required for high affinity protein/DNA binding. As a means to determine the in vivo significance of this recognition site and to identify the key DNA sequence determinants required for ureA transcription, herein, we have translated these in vitro results to analysis directly within H. pylori. Using a series of GFP reporter constructs in which the PureA DNA target was altered, in combination with mutant H. pylori strains deficient in key regulatory proteins, we confirmed the importance of the previously identified HpNikR recognition sequence for HpNikR-dependent ureA transcription. Moreover, we identified a second factor, the HpArsRS two-component system that was required for maximum transcription of ureA. While HpArsRS is known to regulate ureA in response to acid shock, it was previously thought to function independently of HpNikR and to have no role at neutral pH. However, our qPCR analysis of ureA expression in wildtype, ΔnikR and ΔarsS single mutants as well as a ΔarsS/nikR double mutant strain background showed reduced basal level expression of ureA when arsS was absent. Additionally, we determined that both HpNikR and HpArsRS were necessary for maximal expression of ureA under nickel, low pH and combined nickel and low pH stresses. In vitro studies of HpArsR-P with the PureA DNA target using florescence anisotropy confirmed a direct protein/DNA binding interaction. Together, these data support a model in which HpArsRS and HpNikR cooperatively interact to regulate ureA transcription under various environmental conditions. This is the first time that direct "cross-talk" between HpArsRS and HpNikR at

  9. SIGNS OF ACCRETION IN THE ABUNDANCE PATTERNS OF THE COMPONENTS OF THE RS CVn-TYPE ECLIPSING BINARY STAR LX PERSEI

    SciTech Connect

    Kang, Young-Woon; Yushchenko, Alexander V.; Hong, Kyeongsoo; Guinan, Edward F.; Gopka, Vira F. E-mail: yua@sejong.ac.kr

    2013-06-01

    We present spectroscopic observations of LX Per carried out using the Korean Bohyunsan Observatory Echelle Spectrograph (BOES) with spectral resolving power R = 80, 000. The spectrograph was attached to the 1.8 m telescope. The fit of synthetic spectra to the observed spectrum of the system allowed us to find the component parameters and the abundances of chemical elements in the atmospheres of the components. The strong Ca II H and K emissions are confirmed; we also found emission lines in the Ca II reversals' triplet absorptions at the wavelengths of 8498, 8542, and 8662 A in the spectrum of the cooler component of LX Per. A unique photometric solution using the distorted light curves of three different epochs was made. The spot model light curves were fitted to the 1981, 1982, and 1983 observations successfully by adjusting only spot parameters. We could infer that the variation of spot location and size was the main reason for the changing shape of light curves. The main feature of the abundance patterns of both components was the apparent deficiency of heavy (Z > 30) elements. Only elements with strong lines, namely Y and Ba, were detected. Correlations of relative abundances of chemical elements with condensation temperatures and second ionization potentials of these elements, which can be explained by the accretion of dust and gas, were found.

  10. Rotational modulation and flares on RS CVn and BY Dra-type stars. V - Exosat and IUE observations of a flare on EQ Pegasi

    NASA Technical Reports Server (NTRS)

    Haisch, B. M.; Butler, C. J.; Doyle, J. G.; Rodono, M.

    1987-01-01

    Time-trailed UV spectra and a soft X-ray lightcurve were obtained during a flare on the binary dMe star EQ Peg AB. On the basis of solar flare Mg II surface fluxes and an about 70-percent enhancement in the disk-integrated flux during the flare on EQ Peg, it is estimated that the chromospheric flare covered about 1.5 percent of the stellar surface. The size scale is estimated to be comparable to that of a solar two-ribbon flare. This unusual flare is noted to exhibit a low-energy soft X-ray rise phase which is longer than that of most flares; it is longer than the decay phase and peaks much later than the medium energy light curve. Evidence of variable Fe II emission and variable continuum emission in select UV bands during the flare is noted.

  11. PTK2 rs7460 and rs7843014 Polymorphisms and Exceptional Longevity: A Functional Replication Study

    PubMed Central

    Fuku, Noriyuki; He, Zi-hong; Tian, Ye; Arai, Yasumichi; Abe, Yukiko; Murakami, Haruka; Miyachi, Motohiko; Yvert, Thomas; Venturini, Letizia; Santiago, Catalina; Santos-Lozano, Alejandro; Rodríguez, Gabriel; Ricevuti, Giovanni; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro

    2014-01-01

    Abstract Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or PTK2) is an important component of the human interactome and thus is a potential longevity-related protein. Here we studied the association between two PTK2 gene single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional longevity (EL). In addition to gaining insight into their functionality by determining luciferase gene reporter activity, we studied the genotype/allele frequency of these two SNPs among three different cohorts: (1) Spanish centenarians (n=175, 100–111 years, 144 women) and healthy controls (n=355, 20–50 years, 284 women); (2) Italian centenarians (n=79, 100–104 years, 40 women) and controls (n=316, 29–50 years, 156 women); and (3) Japanese centenarians (n=742, 100–116 years, 623 women) and healthy controls (n=499, 23–59 years, 356 women). Both SNPs had functional significance, with the A allele up-regulating luciferase activity compared to the other allele (rs7460 T allele and rs7843014 C allele, respectively). The A allele of both SNPs was negatively associated with EL in the Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001). The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI 4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching EL in the Spanish population. Further research is needed to unveil the mechanisms by which FAK expression could perhaps influence the rate of aging. PMID:24930376

  12. PER1 rs3027172 Genotype Interacts with Early Life Stress to Predict Problematic Alcohol Use, but Not Reward-Related Ventral Striatum Activity

    PubMed Central

    Baranger, David A. A.; Ifrah, Chloé; Prather, Aric A.; Carey, Caitlin E.; Corral-Frías, Nadia S.; Drabant Conley, Emily; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions. PMID:27065929

  13. Stokes IQUV mapping of α2 CVn & other Ap stars using ESPaDOnS and NARVAL

    NASA Astrophysics Data System (ADS)

    Silvester, J.; Kochukhov, O.; Wade, G. A.

    2013-12-01

    New spectral line polarisation observations of 7 bright Ap stars have been obtained with the ESPaDOnS and Narval high resolution spectropolarimeters (Silvester et al. 2012). The aim of this data set is produce a series of surface magnetic field and surface chemistry maps for these Ap stars. We present new magnetic maps for the Ap star α2 CVn using these new data and the MDI inversion code INVERS10. α2 CVn is the first Ap star to be observed during two separate epochs using high resolution phase resolved spectropolarimetric IQUV observations and as such allows us an insight into how stable the surface magnetic structure is over a decade timescale. We show that the new maps give a magnetic field structure consistent with the previous maps obtained by Kochukhov and Wade (2010) from lower quality MuSiCoS spectra taken a decade ago and that the field topology cannot be described by a dipolar or quadrupolar field.

  14. VLBI observations of the RS Canum Venaticorum binary systems UX Arietis and HR 1099 at 1.65 GHz

    NASA Technical Reports Server (NTRS)

    Mutel, R. L.; Doiron, D. J.; Phillips, R. B.; Lestrade, J. F.

    1984-01-01

    VLBI observations of the RS CVn binaries UX Arietis and HR 1099 have been made at 1.65 GHz using a three-element array with a minimum fringe spacing of 11.5 milli-arcsec. Both sources were found to be unresolved within measurement uncertainties. In both cases, the derived upper limit to the source size was comparable to the overall size of each binary system. The lower limits to the brightness temperature were 1.4 x 10 to the 10th K for UX Arietis and 2.9 x 10 to the 10th K for HR 1099. Simultaneous polarization measurements at the VLA showed 4-8 percent circular polarization and less than 2 percent linear polarization. It is found that the data are consistent with gyrosynchrotron emission from a power-law energy distribution of electrons in a magnetic field B less than or approximately equal to 6 gauss.

  15. SMIM1 variants rs1175550 and rs143702418 independently modulate Vel blood group antigen expression

    PubMed Central

    Christophersen, Mikael K.; Jöud, Magnus; Ajore, Ram; Vege, Sunitha; Ljungdahl, Klara W.; Westhoff, Connie M.; Olsson, Martin L.; Storry, Jill R.; Nilsson, Björn

    2017-01-01

    The Vel blood group antigen is expressed on the red blood cells of most individuals. Recently, we described that homozygosity for inactivating mutations in SMIM1 defines the rare Vel-negative phenotype. Still, Vel-positive individuals show great variability in Vel antigen expression, creating a risk for Vel blood typing errors and transfusion reactions. We fine-mapped the regulatory region located in SMIM1 intron 2 in Swedish blood donors, and observed a strong correlation between expression and rs1175550 as well as with a previously unreported tri-nucleotide insertion (rs143702418; C > CGCA). While the two variants are tightly linked in Caucasians, we separated their effects in African Americans, and found that rs1175550G and to a lesser extent rs143702418C independently increase SMIM1 and Vel antigen expression. Gel shift and luciferase assays indicate that both variants are transcriptionally active, and we identified binding of the transcription factor TAL1 as a potential mediator of the increased expression associated with rs1175550G. Our results provide insight into the regulatory logic of Vel antigen expression, and extend the set of markers for genetic Vel blood group typing. PMID:28084402

  16. The VanRS Homologous Two-Component System VnlRSAb of the Glycopeptide Producer Amycolatopsis balhimycina Activates Transcription of the vanHAXSc Genes in Streptomyces coelicolor, but not in A. balhimycina

    PubMed Central

    Kilian, Regina; Frasch, Hans-Joerg; Kulik, Andreas; Wohlleben, Wolfgang

    2016-01-01

    In enterococci and in Streptomyces coelicolor, a glycopeptide nonproducer, the glycopeptide resistance genes vanHAX are colocalized with vanRS. The two-component system (TCS) VanRS activates vanHAX transcription upon sensing the presence of glycopeptides. Amycolatopsis balhimycina, the producer of the vancomycin-like glycopeptide balhimycin, also possesses vanHAXAb genes. The genes for the VanRS-like TCS VnlRSAb, together with the carboxypeptidase gene vanYAb, are part of the balhimycin biosynthetic gene cluster, which is located 2 Mb separate from the vanHAXAb. The deletion of vnlRSAb did not affect glycopeptide resistance or balhimycin production. In the A. balhimycina vnlRAb deletion mutant, the vanHAXAb genes were expressed at the same level as in the wild type, and peptidoglycan (PG) analyses proved the synthesis of resistant PG precursors. Whereas vanHAXAb expression in A. balhimycina does not depend on VnlRAb, a VnlRAb-depending regulation of vanYAb was demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) and RNA-seq analyses. Although VnlRAb does not regulate the vanHAXAb genes in A. balhimycina, its heterologous expression in the glycopeptide-sensitive S. coelicolor ΔvanRSSc deletion mutant restored glycopeptide resistance. VnlRAb activates the vanHAXSc genes even in the absence of VanS. In addition, expression of vnlRAb increases actinorhodin production and influences morphological differentiation in S. coelicolor. PMID:27420548

  17. PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity in Latvians, Lithuanians and Taiwanese

    PubMed Central

    Sjakste, Tatjana; Paramonova, Natalia; Wu, Lawrence Shi-Shin; Zemeckiene, Zivile; Sitkauskiene, Brigita; Sakalauskas, Raimundas; Wang, Jiu-Yao; Sjakste, Nikolajs

    2014-01-01

    PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity was investigated in 1438 unrelated subjects from Latvia, Lithuania and Taiwan. In general, polymorphism of each individual locus showed tendencies similar to determined previously in HapMap populations. Main differences concern Taiwanese and include presence of rs2277460 rare allele A not found before in Asians and absence of rs2295827 rare alleles homozygotes TT observed in all other human populations. Observed patterns of SNPs and haplotype diversity were compatible with expectation of neutral model of evolution. Linkage disequilibrium between the rs2295826 and rs2295827 was detected to be complete in Latvians and Lithuanians (D´ = 1; r2 = 1) and slightly disrupted in Taiwanese (D´ = 0.978; r2 = 0.901). Population differentiation (FST statistics) was estimated from pairwise population comparisons of loci variability, five locus haplotypes and PSMA6 and PSMC6 two locus haplotypes. Latvians were significantly different from all Asians at each of 5 SNPs and from Lithuanians at the rs1048990 and PSMC6 loci. Lithuanian and Asian populations exhibited similarities at the PSMC6 loci and were different at the PSMA6 and PSMA3 SNPs. Considering five locus haplotypes all European populations were significantly different from Asian; Lithuanian population was different from both Latvian and CEU. Allele specific patterns of transcription factor binding sites and splicing signals were predicted in silico and addressed to eventual functionality of nucleotide substitutions and their potential to be involved in human genome evolution and geographical adaptation. Current study represents a novel step toward a systematic analysis of the proteasomal gene genetic diversity in human populations. PMID:25606411

  18. 5-Hydroxytrytophan inhibits tert-butylhydroperoxide (t-BHP)-induced oxidative damage via the suppression of reactive species (RS) and nuclear factor-kappaB (NF-kappaB) activation on human fibroblast.

    PubMed

    Bae, Sung Jin; Lee, Jun Sik; Kim, Ji Min; Lee, Eun Kyeong; Han, Yu Kyeong; Kim, Hyun Jung; Choi, Jehun; Ha, Young Mi; No, Jae-Kyung; Kim, Yun Hee; Yu, Byung Pal; Chung, Hae Young

    2010-05-26

    5-Hydroxytryptophan (5HTP), an analogue of tryptophan, is a precursor of serotonin that also has effective antioxidative and anti-apoptotic properties (1) . However, the cellular mechanisms underlying these properties of 5HTP have not been explored. In this study, we tested the hypothesis that 5HTP exerts its antioxidative action against oxidative stress and inflammation by suppressing the activation of the key pro-inflammatory transcriptional pathways, p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kappaB (NF-kappaB). The study was carried out using human fibroblast cells that were challenged by tert-butylhydroperoxide (t-BHP)-induced oxidative damage. Results show that 5HTP significantly reduced t-BHP-induced oxidative damage in human fibroblast cells, as determined by cell cytotoxicity, intracellular reactive species (RS) and peroxynitrite (ONOO(-)) generation, and inducible nitric oxide synthase expression. Moreover, 5HTP protected human fibroblast cells against t-BHP-induced oxidative DNA damage, as determined by 4,6-diamidino-2-phenlylindole (DAPI) staining. Pretreatment of human fibroblast cells with 5HTP also dose-dependently inhibited glutathione (GSH) depletion, indicating that it protects cells against t-BHP-induced oxidative damage. Western blot analysis revealed that 5HTP also markedly increased Bcl-2 expression and suppressed both p38MAPK and NF-kappaB activation in the t-BHP-treated human fibroblast cells. When these results are taken together, they strongly indicate that 5HTP has beneficial and protective effects against t-BHP-induced cell death in vitro, as demonstrated by its antioxidative and anti-inflammatory actions. Data further showed that the protective mechanisms underlying the actions of 5HTP against oxidative stress-induced damage are associated with RS/ONOO(-) scavenging and the inhibition of lipid peroxidation and GSH depletion.

  19. Line profile asymmetries in chromospherically active stars

    NASA Technical Reports Server (NTRS)

    Dempsey, Robert C.; Bopp, Bernard W.; Strassmeier, Klaus G.; Granados, Arno F.; Henry, Gregory W.; Hall, Douglas S.

    1992-01-01

    A powerful, new probe of chromospheric activity, cross-correlation, has been developed and applied to a variety of stars. In this particular application, an entire CCD spectrum of an active star is correlated with the spectrum of a narrow-line, inactive star of similar spectral type and luminosity class. Using a number of strong lines in this manner enables the detection of absorption profile asymmetries at moderate resolution (lambda/Delta lambda about 40,000) and S/N 150:1. This technique has been applied to 14 systems mostly RS CVn's, with 10 not greater than nu sin i not greater than 50 km/s and P not less than 7 d. Distortions were detected for the first time in five systems: Sigma Gem, IM Peg, GX Lib, UV Crb, and Zeta And. Detailed modeling, incorporating both spectral line profiles and broad-band photometry, is applied to Sigma Gem. Profile asymmetries for this star are fitted by two high-latitude spots covering 5 percent of the stellar surface. The derived spot temperature of 3400 K is lower than found in previous studies. In addition, two well-known systems have been studied: HD 199178 and V711 Tau. Polar spots are found on both.

  20. The period analysis of V418 AQL, SU BOO, RV CVn, CR CAS, GV CYG, V432 PER, and BD+42 2782

    SciTech Connect

    Zasche, P.; Wolf, M.; Kučáková, H.; Uhlař, R.

    2014-06-01

    The minimum timings of eclipsing binaries V418 Aql, SU Boo, RV CVn, CR Cas, GV Cyg, V432 Per, and BD+42 2782 were collected and analyzed. Their long-term behavior was studied via period analysis, revealing a periodic term in eclipse times. We derived 576 new times of minimum. Hence, to describe the periodic variation, a third-body hypothesis was proposed and the resulting orbital periods are as follows: 70, 7.4, 53, 37, 27, 53, and 18 yr, respectively. For the system V432 Per an additional 9.5 yr variation was also found. The predicted minimum masses of these distant bodies were calculated and their detectability discussed. The light curves of SU Boo and RV CVn were analyzed using the PHOEBE program, resulting in physical parameters of the components. New variable stars in the field of V418 Aql were discovered.

  1. Synthesis and biological activity of a novel class nicotinic acetylcholine receptors (nAChRs) ligands structurally related to anatoxin-a.

    PubMed

    Simoni, Daniele; Rondanin, Riccardo; Marchetti, Paolo; Rullo, Cinzia; Baruchello, Riccardo; Grisolia, Giuseppina; Barbato, Giuseppina; Giovannini, Riccardo; Marchioro, Carla; Capelli, Anna Maria; Virginio, Caterina; Bozzoli, Andrea; Borea, Pier Andrea; Merighi, Stefania; Donati, Daniele

    2011-09-15

    The introduction of the isoxazole ring as bioisosteric replacement of the acetyl group of anatoxin-a led to a new series of derivatives binding to nicotinic acetylcholine receptors. Bulkier substitutions than methyl at the 3 position of isoxazole were shown to be detrimental for the activity. The binding potency of the most interesting compounds with α1, α7 and α3β4 receptor subtypes, was, anyway, only at micromolar level. Moreover, differently from known derivatives with pyridine, isoxazole condensed to azabicyclo ring led to no activity.

  2. Nonradial and radial period changes in the δ Scuti star 4 CVn. I. 700+ nights of photometry

    NASA Astrophysics Data System (ADS)

    Breger, M.

    2016-08-01

    Context. The nature of period and amplitude changes in nonradial pulsators is presently unknown. Aims: It is therefore important to examine the correlations between these changes in stars with a large number of simultaneously excited pulsation modes. However, the small amplitudes require extensive high-precision photometry covering many years. Methods: We present 702 nights of high-precision photometry of the evolved δ Sct variable 4 CVn obtained from 2005-2012 with a dedicated telescope. Results: We detected 64 frequencies, of which 38 can be identified as combinations and harmonics. The relative amplitudes of the combination frequencies are similar to those found in 44 Tau and show no evidence for resonant mode coupling. Significant period and amplitude changes are detected for the dominant modes. The known prograde and retrograde modes show period changes with opposite signs, while the radial mode exhibits only small, cyclical period changes. For each mode, the period changes are constant over the eight years and range from (1 /P)dP/ dt = -16 × 10-6 to 13 × 10-6. On the other hand, the amplitude variations show no systematic behavior between different pulsation modes. Conclusions: The behavior of the prograde, axisymmetric, and retrograde modes indicate a constant decrease in the rotational splitting over the eight years.

  3. Masses and radii for thirteen chromospherically active ellipsoidal variables

    NASA Technical Reports Server (NTRS)

    Hall, Douglas S.

    1990-01-01

    The amplitude of the ellipticity effect, the mass function, and the V sin i in ten long-period RS CVn SB1 binaries are used to compute limits on the masses of the two stars and the radius of the primary: zeta And, UV CrB, V1764 Cyg, V826 Her, V350 Lac, GX Lib, V1197 Ori, AP Psc, 33 Psc, and EE UMa. Explicit masses and radii are computed for three SB2 systems: BL CVn, V1817 Cyg, and TZ Tri. The primary in several is found to fill 95 percent or more of its Roche lobe. The two minima produced by the ellipticity effect are unequal in depth, with the effect largest when i is near 90 deg and the primary nearly fills its Roche lobe. The greatest inequality found, in UV CrB, was 0.08 mag.

  4. Different angiogenesis effect of mini-TyrRS/mini-TrpRS by systemic administration of modified siRNAs in rats with acute myocardial infarction.

    PubMed

    Zeng, Rui; Chen, Yu-Cheng; Zeng, Zhi; Liu, Wei-Qiang; Liu, Xiao-Xia; Liu, Rui; Qiang, Ou; Li, Xian

    2010-07-01

    We aimed to clarify the different angiogenesis effects of mini-tyrosyl-tRNA synthetase (TyrRS)/minitryptophanyl-tRNA synthetase (TrpRS) in rodent primates with acute myocardial infarction, by delivering small interfering RNAs (siRNAs) systemically in a liposomal formulation. Left coronary artery ligation was used to establish the model of acute myocardial infarction in rats; mini-TyrRS/mini-TrpRS-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP), and administered by intravenous injection to rats. Rats were divided into four experiment groups: sham operated group (no left anterior descending artery [LAD] occlusion); negative control group (LAD occlusion + saline injection); mock transfection group (LAD occlusion + mock transfected injection); experiment group (LAD occlusion + mini-TyrRS/mini-TrpRS-specific siRNAs injection). Silencing efficiency was assayed by Western blotting. To determine whether mini-TyrRS/mini-TrpRS affected the angiogenesis activity of rats with myocardial infarction, we measured the myocardial infarction size by TTC staining, and the capillary density using immunohistochemistry staining, to investigate the expression of factor VIII. The myocardial infarction size and the capillary density of mini-TyrRS-siRNA group were respectively 18.89% and 8.64/0.1 mm(2) 1 month after ligation, while in the mini-TrpRS-siRNA group these values were 7.33% and 17.32/0.1 mm(2), significantly different compared with the mock transfection group (14.19%; 13.56/0.1 mm(2)) and negative control group (14.28%; 13.89/0.1 mm(2)), P < 0.05. There were no significant changes between the mock transfection group and the negative control group, P > 0.05. These results indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by mini-TrpRS in rat models with acute myocardial infarction.

  5. Transverse and z-Direction CVN Impact Tests of X65 Line Pipe Steels of Two Centerline Segregation Ratings

    NASA Astrophysics Data System (ADS)

    Su, Lihong; Li, Huijun; Lu, Cheng; Li, Jintao; Fletcher, Leigh; Simpson, Ian; Barbaro, Frank; Zheng, Lei; Bai, Mingzhuo; Shen, Jianlan; Qu, Xianyong

    2016-08-01

    Centerline segregation occurs as a positive concentration of alloying elements in the mid-thickness region of continuously cast slab. Depending upon its severity, it may affect mechanical properties and potentially downstream processing such as weldability, particularly for high-strength line pipe. The segregation fraction in continuously cast slabs and corresponding hot-rolled strips was assessed on API 5L grade X65 line pipe steels with different levels of segregation, rated as Mannesmann 2.0 and 1.4. The results showed that the segregation fraction in hot-rolled strip samples was in accordance with that assessed in the cast slabs, and the segregated regions in hot-rolled strip samples were found to be discontinuous. Transverse and z-direction CVN impact tests were conducted on the two strips and the results showed that centerline segregation does have an influence on the Charpy impact properties of line pipe steel. Specimens located at segregated regions exhibited lower Charpy impact toughness and strips rolled from slabs with higher segregation levels are more likely to exhibit greater variability in Charpy impact toughness. The influence of centerline segregation on z-direction Charpy impact toughness is more severe than on transverse Charpy impact toughness. Lower Charpy impact toughness and brittle fracture surface with cleavage facets along with rod-shaped MnS inclusions were observed for the strip rolled from slab with 2.0 segregation rating if the Charpy specimens were located at segregated regions. The influence on Charpy impact toughness can be associated with the pearlite structure at the centerline and level of MnS inclusions.

  6. UVES and X-Shooter spectroscopy of the emission line AM CVn systems GP Com and V396 Hya

    NASA Astrophysics Data System (ADS)

    Kupfer, T.; Steeghs, D.; Groot, P. J.; Marsh, T. R.; Nelemans, G.; Roelofs, G. H. A.

    2016-04-01

    We present time-resolved spectroscopy of the AM CVn-type binaries GP Com and V396 Hya obtained with VLT/X-Shooter and VLT/UV-Visual Echelle Spectrograph (UVES). We fully resolve the narrow central components of the dominant helium lines and determine radial velocity semi-amplitudes of Kspike = 11.7 ± 0.3 km s-1 for GP Com and Kspike = 5.8 ± 0.3 km s-1 for V396 Hya. The mean velocities of the narrow central components show variations from line to line. Compared to calculated line profiles that include Stark broadening we are able to explain the displacements, and the appearance of forbidden helium lines, by additional Stark broadening of emission in a helium plasma with an electron density ne ≃ 5 × 1015 cm-3. More than 30 nitrogen and more than 10 neon lines emission lines were detected in both systems. Additionally, 20 nitrogen absorption lines are only seen in GP Com. The radial velocity variations of these lines show the same phase and velocity amplitude as the central helium emission components. The small semi-amplitude of the central helium emission component, the consistency of phase and amplitude with the absorption components in GP Com as well as the measured Stark effect shows that the central helium emission component, the so-called central-spike, is consistent with an origin on the accreting white dwarf. We use the dynamics of the bright spot and the central-spike to constrain the binary parameters for both systems and find a donor mass of 9.6-42.8 MJupiter for GP Com and 6.1-30.5 MJupiter for V396 Hya. We find an upper limit for the rotational velocity of the accretor of vrot < 46 km s-1 for GP Com and vrot < 59 km s-1 for V396 Hya which excludes a fast rotating accretor in both systems.

  7. A CENSUS OF AM CVn STARS: THREE NEW CANDIDATES AND ONE CONFIRMED 48.3-MINUTE BINARY

    SciTech Connect

    Rau, A.; Roelofs, G. H. A.; Steeghs, D.; Groot, P. J.; Nelemans, G.; Marsh, T. R.; Salvato, M.; Kasliwal, M. M.

    2010-01-01

    We present three new candidate AM CVn binaries, and one confirmed new system, from a spectroscopic survey of color-selected objects from the Sloan Digital Sky Survey (SDSS). All four systems were found from their helium emission lines in low-resolution spectra taken on the Hale telescope at Palomar, the Nordic Optical Telescope, and the William Herschel Telescope on La Palma. The ultra-compact binary nature of SDSS J090221.35+381941.9 was confirmed using phase-resolved spectroscopy at the Keck-I telescope. From the characteristic radial velocity 'S-wave' observed in the helium emission lines, we measure an orbital period of 48.31 +- 0.08 minutes. The continuum emission can be described with a blackbody or a helium white dwarf atmosphere of T{sub eff} approx 15,000 K, in agreement with theoretical cooling models for relatively massive accretors and/or donors. The absence in the spectrum of broad helium absorption lines from the accreting white dwarf suggests that the accreting white dwarf cannot be much hotter than 15,000 K, or that an additional component such as the accretion disk contributes substantially to the optical flux. Two of the candidate systems, SDSS J152509.57+360054.5 and SDSS J172102.48+273301.2, do show helium absorption in the blue part of their spectra in addition to the characteristic helium emission lines. This in combination with the high effective temperatures of approx18,000 K and approx16,000 K suggests both to be at orbital periods below approx40 minutes. The third candidate, SDSS J164228.06+193410.0, exhibits remarkably strong helium emission on top of a relatively cool (T{sub eff} approx 12,000 K) continuum, indicating an orbital period above approx50 minutes.

  8. A Very Bright, Very Hot, and Very Long Flaring Event from the M Dwarf Binary System DG CVn

    NASA Astrophysics Data System (ADS)

    Osten, Rachel A.; Kowalski, Adam; Drake, Stephen A.; Krimm, Hans; Page, Kim; Gazeas, Kosmas; Kennea, Jamie; Oates, Samantha; Page, Mathew; de Miguel, Enrique; Novák, Rudolf; Apeltauer, Tomas; Gehrels, Neil

    2016-12-01

    On 2014 April 23, the Swift satellite responded to a hard X-ray transient detected by its Burst Alert Telescope, which turned out to be a stellar flare from a nearby, young M dwarf binary DG CVn. We utilize observations at X-ray, UV, optical, and radio wavelengths to infer the properties of two large flares. The X-ray spectrum of the primary outburst can be described over the 0.3-100 keV bandpass by either a single very high-temperature plasma or a nonthermal thick-target bremsstrahlung model, and we rule out the nonthermal model based on energetic grounds. The temperatures were the highest seen spectroscopically in a stellar flare, at T X of 290 MK. The first event was followed by a comparably energetic event almost a day later. We constrain the photospheric area involved in each of the two flares to be >1020 cm2, and find evidence from flux ratios in the second event of contributions to the white light flare emission in addition to the usual hot, T ˜ 104 K blackbody emission seen in the impulsive phase of flares. The radiated energy in X-rays and white light reveal these events to be the two most energetic X-ray flares observed from an M dwarf, with X-ray radiated energies in the 0.3-10 keV bandpass of 4 × 1035 and 9 × 1035 erg, and optical flare energies at E V of 2.8 × 1034 and 5.2 × 1034 erg, respectively. The results presented here should be integrated into updated modeling of the astrophysical impact of large stellar flares on close-in exoplanetary atmospheres.

  9. Nonradial and radial period changes of the δ Scuti star 4 CVn. II. Systematic behavior over 40 years

    NASA Astrophysics Data System (ADS)

    Breger, M.; Montgomery, M. H.; Lenz, P.; Pamyatnykh, A. A.

    2017-03-01

    Aims: Radial and nonradial pulsators on and near the main sequence show period and amplitude changes that are too large to be the product of stellar evolution. The multiperiodic δ Sct stars are well suited to study this, as the period changes of different modes excited in the same star can be compared. This requires a very large amount of photometric data covering years and decades as well as mode identifications. Methods: We have examined over 800 nights of high-precision photometry of the multiperiodic pulsator 4 CVn obtained from 1966 through 2012. Because most of the data were obtained in adjacent observing seasons, it is possible to derive very accurate period values for a number of the excited pulsation modes and to study their systematic changes from 1974 to 2012. Results: Most pulsation modes show systematic significant period and amplitude changes on a timescale of decades. For the well-studied modes, around 1986 a general reversal of the directions of both the positive and negative period changes occurred. Furthermore, the period changes between the different modes are strongly correlated, although they differ in size and sign. For the modes with known values of the spherical degree and azimuthal order, we find a correlation between the direction of the period changes and the identified azimuthal order, m. The associated amplitude changes generally have similar timescales of years or decades, but show little systematic or correlated behavior from mode to mode. Conclusions: A natural explanation for the opposite behavior of the prograde and retrograde modes is that their period changes are driven by a changing rotation profile. The changes in the rotation profile could in turn be driven by processes, perhaps the pulsations themselves, that redistribute angular momentum within the star. In general, different modes have different rotation kernels, so this will produce period shifts of varying magnitude for different modes.

  10. Exceptional longevity and muscle and fitness related genotypes: a functional in vitro analysis and case-control association replication study with SNPs THRH rs7832552, IL6 rs1800795, and ACSL1 rs6552828

    PubMed Central

    Fuku, Noriyuki; He, Zi-hong; Sanchis-Gomar, Fabian; Pareja-Galeano, Helios; Tian, Ye; Arai, Yasumichi; Abe, Yukiko; Murakami, Haruka; Miyachi, Motohiko; Zempo, Hirofumi; Naito, Hisashi; Yvert, Thomas; Verde, Zoraida; Venturini, Letizia; Fiuza-Luces, Carmen; Santos-Lozano, Alejandro; Rodriguez-Romo, Gabriel; Ricevuti, Giovanni; Hirose, Nobuyoshi; Emanuele, Enzo; Garatachea, Nuria; Lucia, Alejandro

    2015-01-01

    There are several gene variants that are candidates to influence functional capacity in long-lived individuals. As such, their potential association with exceptional longevity (EL, i.e., reaching 100+ years) deserves analysis. Among them are rs7832552 in the thyrotropin-releasing hormone receptor (TRHR) gene, rs1800795 in the interleukin-6 (IL6) gene and rs6552828 in the coenzyme A synthetase long-chain 1 (ACSL1) gene. To gain insight into their functionality (which is yet unknown), here we determined for the first time luciferase gene reporter activity at the muscle tissue level in rs7832552 and rs6552828. We then compared allele/genotype frequencies of the 3 abovementioned variants among centenarians [n = 138, age range 100–111 years (114 women)] and healthy controls [n = 334, 20–50 years (141 women)] of the same ethnic and geographic origin (Spain). We also studied healthy centenarians [n = 79, 100–104 years (40 women)] and controls [n = 316, 27–81 years (156 women)] from Italy, and centenarians [n = 742, 100–116 years (623 women)] and healthy controls [n = 499, 23–59 years (356 women)] from Japan. The THRH rs7832552 T-allele and ACSL1 rs6552828 A-allele up-regulated luciferase activity compared to the C and G-allele, respectively (P = 0.001). Yet we found no significant association of EL with rs7832552, rs1800795 or rs6552828 in any of the 3 cohorts. Further research is needed with larger cohorts of centenarians of different origin as well as with younger old people. PMID:25999849

  11. Overexpression of Shati/Nat8l, an N-acetyltransferase, in the nucleus accumbens attenuates the response to methamphetamine via activation of group II mGluRs in mice.

    PubMed

    Miyamoto, Yoshiaki; Ishikawa, Yudai; Iegaki, Noriyuki; Sumi, Kazuyuki; Fu, Kequan; Sato, Keiji; Furukawa-Hibi, Yoko; Muramatsu, Shin-Ichi; Nabeshima, Toshitaka; Uno, Kyosuke; Nitta, Atsumi

    2014-08-01

    A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens (NAc) of mice with methamphetamine (METH) treatment. Previously we reported that suppression of Shati/Nat8l enhanced METH-induced behavioral alterations via dopaminergic neuronal regulation. However, the physiological mechanisms of Shati/Nat8l on the dopaminergic system in the brain are unclear. In this study, we injected adeno-associated virus (AAV) vector containing Shati/Nat8l into the NAc or dorsal striatum (dS) of mice, to increase Shati/Nat8l expression. Overexpression of Shati/Nat8l in the NAc, but not in the dS, attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference in mice. Moreover, the Shati/Nat8l overexpression in the NAc attenuated the elevation of extracellular dopamine levels induced by METH in in vivo microdialysis experiments. These behavioral and neurochemical alterations due to Shati/Nat8l overexpression in the NAc were inhibited by treatment with selective group II metabotropic glutamate receptor type 2 and 3 (mGluR2/3) antagonist LY341495. In the AAV vector-injected NAc, the tissue contents of both N-acetylaspartate and N-acetylaspartylglutamate (NAAG), endogenous mGluR3 agonist, were elevated. The injection of peptidase inhibitor of NAAG or the perfusion of NAAG itself reduced the basal levels of extracellular dopamine in the NAc of naive mice. These results indicate that Shati/Nat8l in the NAc, but not in the dS, plays an important suppressive role in the behavioral responses to METH by controlling the dopaminergic system via activation of group II mGluRs.

  12. Phase-resolved spectroscopy and Kepler photometry of the ultracompact AM CVn binary SDSS J190817.07+394036.4

    NASA Astrophysics Data System (ADS)

    Kupfer, T.; Groot, P. J.; Bloemen, S.; Levitan, D.; Steeghs, D.; Marsh, T. R.; Rutten, R. G. M.; Nelemans, G.; Prince, T. A.; Fürst, F.; Geier, S.

    2015-10-01

    Kepler satellite photometry and phase-resolved spectroscopy of the ultracompact AM CVn type binary SDSS J190817.07+394036.4 are presented. The average spectra reveal a variety of weak metal lines of different species, including silicon, sulphur and magnesium as well as many lines of nitrogen, beside the strong absorption lines of neutral helium. The phase-folded spectra and the Doppler tomograms reveal an S-wave in emission in the core of the He I 4471 Å absorption line at a period of Porb = 1085.7 ± 2.8 s identifying this as the orbital period of the system. The Si II, Mg II and the core of some He I lines show an S-wave in absorption with a phase offset of 170° ± 15° compared to the S-wave in emission. The N II, Si III and some helium lines do not show any phase variability at all. The spectroscopic orbital period is in excellent agreement with a period at Porb = 1085.108(9) s detected in the 3 yr Kepler light curve. A Fourier analysis of the Q6-Q17 short-cadence data obtained by Kepler revealed a large number of frequencies above the noise level where the majority shows a large variability in frequency and amplitude. In an Observed-minus-computed analysis, we measured a \\vert dot{P}\\vert ˜ 1.0 × 10-8 s s-1 for some of the strongest variations and set a limit for the orbital period to be \\vert dot{P}\\vert <10^{-10} s s-1. The shape of the phase-folded light curve on the orbital period indicates the motion of the bright-spot. Models of the system were constructed to see whether the phases of the radial velocity curves and the light-curve variation can be combined to a coherent picture. However, from the measured phases neither the absorption nor the emission can be explained to originate in the bright-spot.

  13. Acetylation promotes TyrRS nuclear translocation to prevent oxidative damage

    PubMed Central

    Cao, Xuanye; Li, Chaoqun; Xiao, Siyu; Tang, Yunlan; Huang, Jing; Zhao, Shuan; Li, Xueyu; Li, Jixi; Zhang, Ruilin; Yu, Wei

    2017-01-01

    Tyrosyl-tRNA synthetase (TyrRS) is well known for its essential aminoacylation function in protein synthesis. Recently, TyrRS has been shown to translocate to the nucleus and protect against DNA damage due to oxidative stress. However, the mechanism of TyrRS nuclear localization has not yet been determined. Herein, we report that TyrRS becomes highly acetylated in response to oxidative stress, which promotes nuclear translocation. Moreover, p300/CBP-associated factor (PCAF), an acetyltransferase, and sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, regulate the nuclear localization of TyrRS in an acetylation-dependent manner. Oxidative stress increases the level of PCAF and decreases the level of SIRT1 and deacetylase activity, all of which promote the nuclear translocation of hyperacetylated TyrRS. Furthermore, TyrRS is primarily acetylated on the K244 residue near the nuclear localization signal (NLS), and acetylation inhibits the aminoacylation activity of TyrRS. Molecular dynamics simulations have shown that the in silico acetylation of K244 induces conformational changes in TyrRS near the NLS, which may promote the nuclear translocation of acetylated TyrRS. Herein, we show that the acetylated K244 residue of TyrRS protects against DNA damage in mammalian cells and zebrafish by activating DNA repair genes downstream of transcription factor E2F1. Our study reveals a previously unknown mechanism by which acetylation regulates an aminoacyl-tRNA synthetase, thus affecting the repair pathways for damaged DNA. PMID:28069943

  14. Variability of a Stellar Corona on a Time Scale of Days: Evidence for Abundance Fractionation in an Emerging Coronal Active Region

    NASA Technical Reports Server (NTRS)

    Nordon, R.; Behar, E.; Drake, S. A.

    2013-01-01

    Elemental abundance effects in active coronae have eluded our understanding for almost three decades, since the discovery of the first ionization potential (FIP) effect on the sun. The goal of this paper is to monitor the same coronal structures over a time interval of six days and resolve active regions on a stellar corona through rotational modulation. We report on four iso-phase X-ray spectroscopic observations of the RS CVn binary EI Eri with XMM-Newton, carried out approximately every two days, to match the rotation period of EI Eri. We present an analysis of the thermal and chemical structure of the EI Eri corona as it evolves over the six days. Although the corona is rather steady in its temperature distribution, the emission measure and FIP bias both vary and seem to be correlated. An active region, predating the beginning of the campaign, repeatedly enters into our view at the same phase as it rotates from beyond the stellar limb. As a result, the abundances tend slightly, but consistently, to increase for high FIP elements (an inverse FIP effect) with phase. We estimate the abundance increase of high FIP elements in the active region to be of about 75% over the coronal mean. This observed fractionation of elements in an active region on time scales of days provides circumstantial clues regarding the element enrichment mechanism of non-flaring stellar coronae.

  15. Strong variable linear polarization in the cool active star II Peg

    NASA Astrophysics Data System (ADS)

    Rosén, Lisa; Kochukhov, Oleg; Wade, Gregg A.

    2014-08-01

    Magnetic fields of cool active stars are currently studied polarimetrically using only circular polarization observations. This provides limited information about the magnetic field geometry since circular polarization is only sensitive to the line-of-sight component of the magnetic field. Reconstructions of the magnetic field topology will therefore not be completely trustworthy when only circular polarization is used. On the other hand, linear polarization is sensitive to the transverse component of the magnetic field. By including linear polarization in the reconstruction the quality of the reconstructed magnetic map is dramatically improved. For that reason, we wanted to identify cool stars for which linear polarization could be detected at a level sufficient for magnetic imaging. Four active RS CVn binaries, II Peg, HR 1099, IM Peg, and σ Gem were observed with the ESPaDOnS spectropolarimeter at the Canada-France-Hawaii Telescope. Mean polarization profiles in all four Stokes parameters were derived using the multi-line technique of least-squares deconvolution (LSD). Not only was linear polarization successfully detected in all four stars in at least one observation, but also, II Peg showed an extraordinarily strong linear polarization signature throughout all observations. This qualifies II Peg as the first promising target for magnetic Doppler imaging in all four Stokes parameters and, at the same time, suggests that other such targets can possibly be identified.

  16. Small interfering RNA knockdown of mini-TyrRS and mini-TrpRS effects angiogenesis in human umbilical vein endothelial cells in hypoxic culture.

    PubMed

    Zeng, Rui; Chen, Yu-Cheng; Zeng, Zhi; Liu, Rui; Qiang, Ou; Jiang, Xiao-Fei; Liu, Xiao-Xia; Li, Xian; Wang, Hao-Yu

    2008-03-01

    Aim We studied the role of mini-TyrRS and mini-TrpRS in angiogenesis by using small interfering RNA-mediated mini-TyrRS/mini-TrpRS knockout in hypoxic culture of human umbilical vein endothelial cells. Methods SiRNA was used as the main method to inhibited the gene function. Silencing efficiency was assayed by real-time reverse transcription-polymerase chain reaction and western blotting. The angiogenic activity in vitro was evaluated by transwell migration assay and Matrigel-induced capillary tube formation in hypoxic culture. Cell proliferation was determined by crystal violet staining. Results The results showed that levels of the mini-TyrRS/mini-TrpRS gene and protein in mock transfection group and negative control group were higher, but noticeably decreased in experimental group. However, no significant difference was detected between mock transfection group and negative control group, but there was a statistically significant difference compared with experimental group. For mini-TyrRS-siRNA group, the cell migration, tube formation and the rate of cell proliferation were respectively inhibited by (47.4, 56.3, 65.4, 73.7%), (60.5, 69.1, 75.9, 83.6%) and (40.4, 56.2, 61.2, 68.0%). For mini-TrpRS-siRNA, were respectively increased by (18.0, 33.8, 45.1, 56.4%), (18.3, 31.2, 40.3, 45.7%) and (8.4, 26.4, 38.2, 46.6%). Conclusion These results indicated that angiogenesis is either stimulated by mini-TyrRS or inhibited by mini-TrpRS in matrigel models in hypoxic culture, raising the possibility that mini-TyrRS stimulates a common downstream signaling event. Thus, naturally occurring fragments of two proteins involved in translation, TyrRS and TrpRS, have opposing activity on endothelial cell angiogenesis in the matrigel assays. The opposing activities of the two tRNA synthetases suggest tight regulation of the balance between pro- and anti-angiogenic stimuli.

  17. Enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin under field conditions.

    PubMed

    Wang, Xiangyun; Qi, Peipei; Yang, Guiling; Wang, Xinquan; Zhang, Hu; Xu, Hao; Wang, Zhiwei; Wang, Qiang

    2014-08-01

    In this study we investigated the enantioselective degradation of (2RS,3RS)-paclobutrazol in peach and mandarin fruits under field conditions after foliar treatment at 500 mg active ingredient/L using a Lux Cellulose-1 chiral column on a reverse-phase liquid chromatography-tandem mass spectrometry system. Degradations of paclobutrazol in both fruits followed first-order kinetics, with half-lives of about 9 days. Initial deposits were 1.63 mg/kg on peach and 1.99 mg/kg on mandarin; terminal concentrations were lower than 0.05 mg/kg, which was acceptable in most cases. As anticipated, paclobutrazol levels in peels of mature mandarin were about 6.3 times higher than in pulp, indicating the potential risk of peel consumption. We also observed that paclobutrazol degradation in mature mandarin was relatively slow, indicating it might not be efficient enough to hold mandarin fruits on trees for lowering paclobutrazol concentrations. Significant enantioselectivity was observed: the (2R,3R)-enantiomer was preferentially degraded in mandarin (whole fruit, peels, and pulp) but enriched in peach. Because of its more rapid degradation in mandarin and the lower levels observed in pulp compared with peels, potential endocrine-related side effects due to the (2R,3R)-enantiomer pose less of a risk in mandarin than in peach.

  18. Goddard High Resolution Spectrograph Observations of Variability in the RS Canum Venaticorum System V711 Tauri (HR 1099)

    NASA Technical Reports Server (NTRS)

    Dempsey, Robert C.; Neff, James E.; Thorpe, Marjorie J.; Linsky, Jeffrey L.; Brown, Alexander; Cutispoto, Giuseppe; Rodono, Marcello

    1996-01-01

    Goddard High Resolution Spectrograph (GHRS) observations of the RS CVn-type binary V711 Tau (Kl IV+G5 IV) were obtained at several phases over two consecutive stellar orbital cycles in order to study ultraviolet emission-line profile and flux variability. Spectra cover the Mg II h and k lines, C IV doublet, and Si IV region, as well as the density-sensitive lines of C III] (1909 A) and Si III] (1892 A). IUE spectra, Extreme Ultra Violet (EUV) data, and Ultraviolet, Blue, Visual (UBV) photometry were obtained contemporaneously with the GHRS data. Variable extended wings were detected in the Mg II lines. We discuss the Mg II line profile variability using various Gaussian emission profile models. No rotational modulation of the line profiles was observed, but there were several large flares. These flares produced enhanced emission in the extended line wings, radial velocity shifts, and asymmetries in some line profiles. Nearly continuous flaring for more than 24 hr, as indicated in the IUE data, represents the most energetic and long-lived chromospheric and transition region flare ever observed with a total energy much greater than 5 x 10(exp 35) ergs. The C III] to Si III] line ratio is used to estimate the plasma density during the flares.

  19. Systematic Pressure and Temperature Differences between Vaisala RS80 and RS92 Radiosonde-Systems

    NASA Astrophysics Data System (ADS)

    Steinbrecht, W.; Claude, H.; Schönenborn, F.

    2008-12-01

    National meteorological centers are replacing the widely used Vaisala RS80 radiosonde with the newer RS90 or RS92. Such change-overs often introduce erroneous steps into long-term atmospheric temperature records. We show that twin-flight campaigns with RS80 and RS92 sondes on the same balloon, and the transition from RS80 to RS92 in operational radio-soundings over Germany, consistently indicate higher temperature readings from RS92 sondes in the stratosphere. In our presentation we summarize these main differences between RS80 and RS92. Significant differences are found in the stratosphere, above the 100~hPa level. The accuracy of our temperature results is of the order of 0.1 to 0.5~K, and at this level we were not able to find significant differences in the troposphere, although there are indications for slightly higher daytime temperatures from RS92 sondes. During day-time and near 50~hPa, RS92s report +0.3 ± 0.2~K higher temperature than RS80s, increasing to +0.7 ± 0.4~K near 10~hPa (2σ uncertainties). At night, the difference is smaller, +0.1 ± 0.1~K near 50~hPa to +0.35 ± 0.2~K near 10~hPa. The mean day-to-night difference (12-00~UT) is also larger for RS92s, by 0.1± 0.06~K near 70~hPa, and by 0.76± 0.16~K near 10~hPa. The main contribution to this stratospheric day-time difference comes from an over-correction of the radiation error in the Vaisala RS80 data processing. The night-time difference at stratospheric levels (and part of the day-time difference) is due to a low bias of the RS80 pressure measurement, typically by -0.4~hPa near 10~hPa. This shifts temperature readings to lower pressure/ higher altitude. For stratospheric levels, it results in lower temperatures from RS80 sondes (due to the vertical temperature increase). Generally, RS92s give better temperature repeatabiliy, ±0.25~K (2σ) near 50~hPa, and much more precise pressure, ±0.2~hPa near 50~hPa, compared to RS80 systems, ±0.5~K, or ±1.5~hPa. Geopotential heights from RS92s are

  20. Search for RS-gravitons at CDF

    SciTech Connect

    Strologas, John; /New Mexico U.

    2011-09-01

    We present a search for Randall-Sundrum (RS) gravitons decaying to diphotons or dielectrons or dimuons, performed with the CDF II detector and using up to 5.7 fb{sup -1} of integrated luminosity. The respective mass spectra are consistent with the ones expected by the standard model. For the RS-model parameter k/{bar M}{sub Pl} = 0.1, RS-gravitons with mass less than 1111 GeV/c{sup 2} are excluded at 95% CL.

  1. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

    SciTech Connect

    Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; Lehtinen, Raisa; Baxter, Shannon; Toto, Tami; Johnson, Karen L.

    2016-06-20

    In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 and RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.

  2. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains Site

    SciTech Connect

    Jensen, M. P.; Holdridge, D.; Survo, P.; Lehtinen, R.; Baxter, S.; Toto, T.; Johnson, K. L.

    2015-11-02

    In the fall of 2013, the Vaisala RS41-SG (4th generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity and pressure. Thus, in order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Facility site in north Central Oklahoma USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results suggest that the RS92 and RS41 measurements generally agree within manufacturer specified tolerances with notable exceptions when exiting liquid cloud layers where the "wet bulbing" effect is mitigated in the RS41 observations. The RS41 measurements also appear to show a smaller impact from solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions, but under most observational conditions the RS41 and RS92 measurements agree within the manufacturer specified limits and so a switch to RS41 radiosondes will have little impact on long-term observational records.

  3. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains Site

    DOE PAGES

    Jensen, M. P.; Holdridge, D.; Survo, P.; ...

    2015-11-02

    In the fall of 2013, the Vaisala RS41-SG (4th generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity and pressure. Thus, in order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Facility site in north Central Oklahoma USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results suggest that the RS92 and RS41 measurements generally agree within manufacturermore » specified tolerances with notable exceptions when exiting liquid cloud layers where the "wet bulbing" effect is mitigated in the RS41 observations. The RS41 measurements also appear to show a smaller impact from solar heating. These results suggest that the RS41 does provide important improvements, particularly in cloudy conditions, but under most observational conditions the RS41 and RS92 measurements agree within the manufacturer specified limits and so a switch to RS41 radiosondes will have little impact on long-term observational records.« less

  4. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

    SciTech Connect

    Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; Lehtinen, Raisa; Baxter, Shannon; Toto, Tami; Johnson, Karen L.

    2016-07-20

    In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 and RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. In addition, these results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.

  5. Role of redoximiRs in fibrogenesis.

    PubMed

    Fierro-Fernández, Marta; Miguel, Verónica; Lamas, Santiago

    2016-04-01

    Fibrosis can be defined as an excessive accumulation of extracellular matrix (ECM) components, ultimately leading to stiffness, scarring and devitalized tissue. MicroRNAs (miRNAs) are short, 19-25 nucleotides (nt), non-coding RNAs involved in the post-transcriptional regulation of gene expression. Recently, miRNAs have also emerged as powerful regulators of fibrotic processes and have been termed "fibromiRs". Oxidative stress represents a self-perpetuating mechanism in fibrogenesis. MiRNAs can also influence the expression of genes responsible for the generation of reactive oxygen species (ROS) and antioxidant defence and are termed "redoximiRs". Here, we review the current knowledge of mechanisms by which "redoximiRs" regulate fibrogenesis. This new set of miRNAs may be called "redoxifibromiRs".

  6. Stress-responsive gene RsICE1 from Raphanus sativus increases cold tolerance in rice.

    PubMed

    Man, Lili; Xiang, Dianjun; Wang, Lina; Zhang, Weiwei; Wang, Xiaodong; Qi, Guochao

    2017-03-01

    The ICE1 transcription factor plays a critical role in plant cold tolerance via triggering CBF/DREB1 cold-regulated signal networks. In this work, a novel MYC-type ICE1-like gene, RsICE1, was isolated from radish (Raphanus sativus L.), and its function in cold tolerance was characterized in rice. The RsICE1 gene was expressed constitutively with higher transcriptional levels in the roots and stems of radish seedlings. The NaCl, cold, and ABA treatments could significantly upregulate RsICE1 expression levels, but dehydration stress had a weak effect on its expression. Ectopic expression of the RsICE1 gene in rice conferred enhanced tolerance to low-temperature stress grounded on a higher survival rate, higher accumulation of soluble sugars and free proline content, a decline in electrolyte leakage and MDA levels, and higher chlorophyll levels relative to control plants. OsDREBL and OsTPP1, downstream cold-regulated genes, were remarkably upregulated at transcription levels in rice overexpressing RsICE1 under low-temperature stress, which indicated that RsICE1 was involved in CBF/DREB1 cold-regulated signal networks. Overall, the above data showed that RsICE1 played an active role in improving rice cold tolerance, most likely resulting from the upregulation of OsDREBL and OsTPP1 expression levels by interacting with the RsICE1 gene under low-temperature stress.

  7. p15RS Attenuates Wnt/β-Catenin Signaling by Disrupting β-Catenin·TCF4 Interaction*

    PubMed Central

    Wu, Yinyuan; Zhang, Yanquan; Zhang, Haiwei; Yang, Xi; Wang, Yinyin; Ren, Fangli; Liu, Huitu; Zhai, Yonggong; Jia, Baoqing; Yu, Jun; Chang, Zhijie

    2010-01-01

    The formation of a β-catenin·TCF4 complex in the nucleus of cells is well known as a prerequisite for the transcription of Wnt target genes. Although many co-factors have been identified to regulate the activity of the β-catenin·TCF4 complex, it remains unclear how the complex association is negatively regulated. In this study, we report that p15RS, a negative regulator of the cell cycle, blocks β-catenin·TCF4 complex formation and inhibits Wnt signaling. We observed that p15RS interacts with β-catenin and TCF4. Interestingly, whereas the interaction of p15RS with β-catenin is increased, its interaction with TCF4 is decreased upon Wnt1 stimulation. Moreover, overexpression of p15RS reduces the interaction of β-catenin with TCF4, whereas the depletion of p15RS enhances their interaction. We further demonstrate that overexpression of p15RS suppresses canonical Wnt signaling and results in retarded cell growth, whereas depletion of p15RS shows an enhanced effect on Wnt signaling. We analyzed that inhibition of Wnt signaling by p15RS leads to decreased expression of CYCLIN D1 and c-MYC, two Wnt targeted genes critical for cell growth. Our data suggest that p15RS inhibits Wnt signaling by interrupting β-catenin·TCF4 complex formation and that Wnt signaling initiates downstream gene expression by removing p15RS from promoters. PMID:20739273

  8. Comparison of Vaisala radiosondes RS41 and RS92 at the ARM Southern Great Plains site

    DOE PAGES

    Jensen, Michael P.; Holdridge, Donna J.; Survo, Petteri; ...

    2016-07-20

    In the fall of 2013, the Vaisala RS41 (fourth generation) radiosonde was introduced as a replacement for the RS92-SGP radiosonde with improvements in measurement accuracy of profiles of atmospheric temperature, humidity, and pressure. In order to help characterize these improvements, an intercomparison campaign was undertaken at the US Department of Energy's Atmospheric Radiation Measurement (ARM) Climate Research Facility site in north-central Oklahoma, USA. During 3–8 June 2014, a total of 20 twin-radiosonde flights were performed in a variety of atmospheric conditions representing typical midlatitude continental summertime conditions. The results show that for most of the observed conditions the RS92 andmore » RS41 measurements agree much better than the manufacturer-specified combined uncertainties with notable exceptions when exiting liquid cloud layers where the “wet-bulbing” effect appears to be mitigated for several cases in the RS41 observations. The RS41 measurements of temperature and humidity, with applied correction algorithms, also appear to show less sensitivity to solar heating. In addition, these results suggest that the RS41 does provide important improvements, particularly in cloudy conditions. For many science applications – such as atmospheric process studies, retrieval development, and weather forecasting and climate modeling – the differences between the RS92 and RS41 measurements should have little impact. However, for long-term trend analysis and other climate applications, additional characterization of the RS41 measurements and their relation to the long-term observational records will be required.« less

  9. MAOA rs1137070 and heroin addiction interactively alter gray matter volume of the salience network

    PubMed Central

    Sun, Yan; Liu, Linwen; Feng, Jiajia; Yue, Weihua; Lu, Lin; Fan, Yong; Shi, Jie

    2017-01-01

    The rs1137070 polymorphism of monoamine oxidase A (MAOA) is associated with alcoholism and smoking behavior. However, the association between rs1137070 and heroin addiction remains unclear. In this study, we examined the allelic distribution of rs1137070 in 1,035 heroin abusers and 2,553 healthy controls and investigated the interactive effects of rs1137070 and heroin addiction on gray matter volume (GMV) based on 78 heroin abusers and 79 healthy controls. The C allele frequency of rs1137070 was significantly higher in heroin abusers. Heroin addiction and the rs1137070 variant interactively altered measures of GMV in the anterior cingulate cortex, orbital frontal cortex, temporal pole, and insula, which were correlated with cognitive function. Heroin abusers with the C allele had lower measures of GMV in these regions than the healthy controls with the same allele, whereas those with the T allele displayed a different trend. The altered brain regions were connected with white matter tracts, yielding a structural network that partially overlapped with the salience network. These findings suggest that the low activity-related C allele of MAOA rs1137070 is associated with an increase in the sensitivity to heroin addiction and the damaging effects of heroin abuse on cognition and the salience network. PMID:28345608

  10. A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria.

    PubMed

    Marquet, Sandrine; Conte, Ianina; Poudiougou, Belco; Argiro, Laurent; Dessein, Hélia; Couturier, Charlène; Burté, Florence; Oumar, Aboubacar A; Brown, Biobele J; Traore, Abdoualye; Afolabi, Nathaniel K; Barry, Abdoulaye; Omokhodion, Samuel; Shokunbi, Wuraola A; Sodeinde, Olugbemiro; Doumbo, Ogobara; Fernandez-Reyes, Delmiro; Dessein, Alain J

    2017-01-31

    Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali. Two SNPs of IL22, rs1012356 (P = 0.016, OR = 2.12) and rs2227476 (P = 0.007, OR = 2.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (P = 0.01) was replicated in 240 nuclear families with one affected child from Mali. SNP rs2227473, in linkage disequilibrium with rs2227476, was also associated with CM in the combined cohort for these two populations, (P = 0.004, OR = 1.55). SNP rs2227473 is located within a putative binding site for the aryl hydrocarbon receptor, a master regulator of IL-22 production. Individuals carrying the aggravating T allele of rs2227473 produced significantly more IL-22 than those without this allele. Overall, these findings suggest that IL-22 is involved in the pathogenesis of CM.

  11. Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis.

    PubMed

    Ojo, Kayode K; Ranade, Ranae M; Zhang, Zhongsheng; Dranow, David M; Myers, Janette B; Choi, Ryan; Nakazawa Hewitt, Steve; Edwards, Thomas E; Davies, Douglas R; Lorimer, Donald; Boyle, Stephen M; Barrett, Lynn K; Buckner, Frederick S; Fan, Erkang; Van Voorhis, Wesley C

    2016-01-01

    We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment.

  12. Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target for Brucellosis

    PubMed Central

    Ranade, Ranae M.; Zhang, Zhongsheng; Dranow, David M.; Myers, Janette B.; Choi, Ryan; Nakazawa Hewitt, Steve; Edwards, Thomas E.; Davies, Douglas R.; Lorimer, Donald; Boyle, Stephen M.; Barrett, Lynn K.; Buckner, Frederick S.; Fan, Erkang; Van Voorhis, Wesley C.

    2016-01-01

    We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with molecular, structural and phenotypic methods to learn if BmMetRS is a promising target for brucellosis drug development. Recombinant BmMetRS was expressed, purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP #DD-156 and screened by a thermal melt assay against a focused library of one hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood stage form of Trypanosoma brucei. Three compounds showed appreciable shift of denaturation temperature and were selected for further studies on inhibition of the recombinant enzyme activity and cell viability against wild type B. melitensis strain 16M. BmMetRS protein complexed with these three inhibitors resolved into three-dimensional crystal structures and was analyzed. All three selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS enzymatic functions in an aminoacylation assay at varying concentrations. Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS is a promising target for brucellosis drug development. However, further studies are needed to optimize lead compound potency, efficacy and safety as well as determine the pharmacokinetics, optimal dosage, and duration for effective treatment. PMID:27500735

  13. Associations between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer

    PubMed Central

    Zhang, Wei; Zhang, Zhifen

    2016-01-01

    Recent studies explored XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian cancer (OC) risk. However, the association between these two single nucleotide polymorphisms and OC risk remains conflicting. Thus, we conducted a comprehensive systematic review and meta-analysis to investigate the association. We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using fixed-effect or random-effect models. 15 case-control studies published in 11 papers including 4,757 cases and 8,431 controls were included in this meta-analysis. No associations were obtained between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and OC risk. Stratification analyses of Hardy–Weinberg equilibrium status indicated that rs3218536 polymorphism was associated with the decreased risk of OC when in analysis of combined HWE positive studies. In conclusion, this meta-analysis indicates that XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms may not be associated with the risk of OC. PMID:27863412

  14. Positive association between PPARD rs2016520 polymorphism and coronary heart disease in a Han Chinese population.

    PubMed

    Ye, H D; Li, Y R; Hong, Q X; Zhou, A N; Zhao, Q L; Xu, L M; Xu, M Q; Xu, X T; Tang, L L; Dai, D J; Jiang, D J; Huang, Y; Wang, D W; Duan, S W

    2015-06-11

    PPARD encodes peroxisome proliferator-activated re-ceptor delta, which has been shown to play an important role in control-ling lipid metabolism and atherosclerosis. In this case-control study, we explored the relationship between PPARD rs2016520 polymorphism and coronary heart disease (CHD) in a Han Chinese population. A to-tal of 657 CHD cases and 640 controls were included in the associa-tion study. rs2016520 polymorphism genotyping was performed using the melting temperature-shift polymerase chain reaction method. The PPARD rs2016520-G allele reduced CHD risk by 17.9% (χ(2) = 5.061, P = 0.025, OR = 0.821, 95%CI = 0.692-0.975). Furthermore, a signifi-cant difference in CHD risk was observed for the PPARD rs2016520 polymorphism in the dominant model (AG + GG vs AA: χ(2) = 4.751, degrees of freedom (df) = 1, P = 0.029, OR = 0.784, 95%CI = 0.631- 0.976). Analysis by age suggested that the G-allele decreased CHD risk by 14.8% in ages greater than 65 years (χ(2) = 4.446, P = 0.035, OR = 0.852, 95%CI = 0.684-1.060). In contrast, meta-analysis of PPARD rs2016520 among 3732 cases and 5042 controls revealed no associa-tion between PPARD rs2016520 and CHD (P = 0.19). We found that the PPARD rs2016520-GG genotype decreased CHD risk in a Han Chinese population. Moreover, we found an association between serum high-density lipoprotein cholesterol level and PPARD rs2016520 in senior individuals aged ≥ 65 years. The meta-analysis revealed no association between PPARD rs2016520 and CHD, suggesting ethnic differences in the association between the PPARD locus and CHD.

  15. XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk.

    PubMed

    Pérez, Luis Orlando; Crivaro, Andrea; Barbisan, Gisela; Poleri, Lucia; Golijow, Carlos Daniel

    2013-07-01

    Human Papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesions. Transformation may be induced by several mechanisms, including oncogene activation and genome instability. Individual differences in DNA damage recognition and repair have been hypothesized to influence cervical cancer risk. The aim of this study was to evaluate whether the double strand break gene polymorphisms XRCC2 R188H G>A (rs3218536), XRCC3 T241M C>T (rs861539) and R243H G>A (rs77381814) are associated to cervical cancer in Argentine women. A case control study consisting of 322 samples (205 cases and 117 controls) was carried out. HPV DNA detection was performed by PCR and genotyping of positive samples by EIA (enzyme immunoassay). XRCC2 and 3 polymorphisms were determined by pyrosequencing. The HPV-adjusted odds ratio (OR) of XRCC2 188 GG/AG genotypes was OR = 2.4 (CI = 1.1-4.9, p = 0.02) for cervical cancer. In contrast, there was no increased risk for cervical cancer with XRCC3 241 TT/CC genotypes (OR = 0.48; CI = 0.2-1; p = 0.1) or XRCC3 241 CT/CC (OR = 0.87; CI = 0.52-1.4; p = 0.6). Regarding XRCC3 R243H, the G allele was almost fixed in the population studied. In conclusion, although the sample size was modest, the present data indicate a statistical association between cervical cancer and XRCC2 R188H polymorphism. Future studies are needed to confirm these findings.

  16. Smoking attenuated the association between IκBα rs696 polymorphism and defective spermatogenesis in humans.

    PubMed

    Yu, B; Ding, Q; Zheng, T; Jiang, L; Li, Q; Sun, X; Bai, C; Huang, Z

    2015-11-01

    Defective spermatogenesis is prevalent in infertile men, but the molecular mechanisms underlying its aetiology are largely unknown. In this study, a proposed association between IκBα SNPs, smoking-related ROS and sperm quality was investigated. Two polymorphisms in the IκBα gene, rs2233406 and rs696 were genotyped in 342 controls and 338 patients with defective spermatogenesis from a southern Chinese population. The results showed the rs696 AA genotype to be significantly more common (21.60% versus 14.33%, P = 0.013) and the rs696 GG genotype to be significantly rarer (28.99% versus 37.13%, P = 0.024) in the cases than in the controls. After subjects were stratified into smokers and nonsmokers, these differences were only observed in nonsmokers. Further analysis showed the rs696 AA genotype to be significantly closely associated with defective spermatogenesis in all subjects (P = 0.014, OR = 1.647) and in nonsmokers (P = 0.036, OR = 1.889). In a TM3 cell model, exposure to cigarette smoke condensate was found to activate NF-κB luciferase activity and altered transcriptional level of NF-κB pathway genes. In conclusion, this study demonstrates an association between functional polymorphisms of the IκBα rs696 and cigarette smoking with the risk of defective spermatogenesis, suggesting some interaction between the NF-κB signalling pathway and smoking-related ROS in human spermatogenesis.

  17. Magnetic activity and orbital period variation of the short-period eclipsing binary DV Psc

    SciTech Connect

    Pi, Qing-feng; Zhang, Li-Yun; Zhang, Xi-liang

    2014-03-01

    We present six new BVR{sub c}I{sub c} CCD light curves of a short-period RS CVn binary DV Psc obtained in 2010-2012. The light curve distortions change on both short and long timescales, which is explained by two starspots on the primary component. Moreover, five new flare events were detected and the flare ratio of DV Psc is about 0.082 flares per hour. There is a possible relation between the phases (longitude) of the flares and starspots for all of the available data of late-type binaries, which implies a correlation of the stellar activity of the spots and flares. The cyclic oscillation, with a period of 4.9 ± 0.4 yr, may result from the magnetic activity cycle, identified by the variability of Max. I-Max. II. Until now, there were no spectroscopic studies of chromospheric activity indicators of the H{sub β} and H{sub γ} lines for DV Psc. Our observations of these indicators show that DV Psc is active, with excess emissions. The updated O – C diagram with an observing time span of about 15 yr shows an upward parabola, which indicates a secular increase in the orbital period of DV Psc. The orbital period secularly increases at a rate of dP/dt = 2.0×10{sup –7} days yr{sup –1}, which might be explained by the angular momentum exchanges or mass transfer from the secondary to primary component.

  18. Bone mineral density is associated with vitamin D related rs6013897 and estrogen receptor polymorphism rs4870044: The Tromsø study

    PubMed Central

    Jorde, Rolf; Emaus, Nina; Eggen, Anne Elise; Joakimsen, Ragnar Martin; Kamycheva, Elena

    2017-01-01

    Background Bone mineral density (BMD) is determined by bone remodeling processes regulated by endocrine, autocrine and genetic mechanisms. Thus, some studies have reported that BMD is associated with single nucleotide polymorphisms (SNPs) associated with vitamin D receptor (VDR), serum 25(OH)D levels and estrogen receptor 1 (ESR1), but without consensus. Therefore, we aimed to map and compare the risk genotypes for forearm and total hip low BMD. Methods and findings Data were derived from a population-based study in northern Norway; the Tromsø Study. Distal forearm BMD was measured with a single x-ray absorptiometric device, while total hip BMD was measured with a dual-energy x-ray absorptiometric device. There were 7,317 and 4,082 successful analyses of distal forearm and total hip BMD, respectively, and at least one SNP of interest. We evaluated plausible BMD modulating factors and associations of BMD and SNPs related to vitamin D metabolism (FokI, Cdx2, BsmI, rs2298850, rs10741657, rs3794060, rs6013897), ApaI-BsmI-TaqI haplotypes and ESR1 SNP rs4870044. Results Age, BMI, physical activity and smoking were significantly associated with BMD. In a linear regression model with adjustment for age and gender and with the major homozygote as reference, rs6013897 had a standardized beta coefficient (β) of –0.031 (P = 0.024) for total hip BMD. β for ESR1 SNP rs4870044 was –0.016 (P = 0.036) for forearm BMD and –0.034 (P = 0.015) for total hip BMD. The other SNPs nor serum 25(OH)D were significantly associated with BMD. Conclusions Both forearm and total hip BMD were associated with ESR1 SNP rs4870044. Of the vitamin D–related genes, only CYP24A1 gene rs6013897 was associated with total hip BMD, but the association was weak and needs confirmation in other studies. Serum 25(OH)D was not associated with BMD in our population, probably due to the generally sufficient vitamin D levels in the population. PMID:28253304

  19. 40 CFR 180.1114 - Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae 742RS...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas syringae 742RS; exemptions from the requirement of a tolerance... Tolerances § 180.1114 Pseudomonas fluorescens A506, Pseudomonas fluorescens 1629RS, and Pseudomonas...

  20. AB111. Genetic variations rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population

    PubMed Central

    Zhang, Yu; Hu, Hailong; Tian, Dawei; Wu, Changli

    2016-01-01

    Objective Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Methods we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. Results We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer [adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09–0.81; P=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10–2.91; P=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (P>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. Conclusions The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population.

  1. The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

    PubMed Central

    Thevissen, Karin; de Mello Tavares, Patricia; Xu, Deming; Blankenship, Jill; Vandenbosch, Davy; Idkowiak-Baldys, Jolanta; Govaert, Gilmer; Bink, Anna; Rozental, Sonia; de Groot, Piet W.J.; Davis, Talya R.; Kumamoto, Carol A.; Vargas, Gabriele; Nimrichter, Leonardo; Coenye, Tom; Mitchell, Aaron; Roemer, Terry; Hannun, Yusuf A.; Cammue, Bruno P.A.

    2012-01-01

    Summary The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2,868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analyzed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation. PMID:22384976

  2. Mass and Reliability System (MaRS)

    NASA Technical Reports Server (NTRS)

    Barnes, Sarah

    2016-01-01

    The Safety and Mission Assurance (S&MA) Directorate is responsible for mitigating risk, providing system safety, and lowering risk for space programs from ground to space. The S&MA is divided into 4 divisions: The Space Exploration Division (NC), the International Space Station Division (NE), the Safety & Test Operations Division (NS), and the Quality and Flight Equipment Division (NT). The interns, myself and Arun Aruljothi, will be working with the Risk & Reliability Analysis Branch under the NC Division's. The mission of this division is to identify, characterize, diminish, and communicate risk by implementing an efficient and effective assurance model. The team utilizes Reliability and Maintainability (R&M) and Probabilistic Risk Assessment (PRA) to ensure decisions concerning risks are informed, vehicles are safe and reliable, and program/project requirements are realistic and realized. This project pertains to the Orion mission, so it is geared toward a long duration Human Space Flight Program(s). For space missions, payload is a critical concept; balancing what hardware can be replaced by components verse by Orbital Replacement Units (ORU) or subassemblies is key. For this effort a database was created that combines mass and reliability data, called Mass and Reliability System or MaRS. The U.S. International Space Station (ISS) components are used as reference parts in the MaRS database. Using ISS components as a platform is beneficial because of the historical context and the environment similarities to a space flight mission. MaRS uses a combination of systems: International Space Station PART for failure data, Vehicle Master Database (VMDB) for ORU & components, Maintenance & Analysis Data Set (MADS) for operation hours and other pertinent data, & Hardware History Retrieval System (HHRS) for unit weights. MaRS is populated using a Visual Basic Application. Once populated, the excel spreadsheet is comprised of information on ISS components including

  3. Nucleotide sequence analysis of pRS2 and pRS3, two small cryptic plasmids from Oenococcus oeni.

    PubMed

    Mesas, J M; Rodríguez, M C; Alegre, M T

    2001-09-01

    Nucleotide sequence analysis of two cryptic plasmids, pRS2 (2544 bp) and pRS3 (3948 bp), from Oenococcus oeni revealed the presence in both of three major open reading frames with significant similarity to other small cryptic plasmids from O. oeni. The results suggest that those plasmids could be separated into two subfamilies, one represented by pLo13 and pRS3, the other represented by pOg32, pRS1, and pRS2.

  4. The atypical antipsychotic olanzapine disturbs depotentiation by modulating mAChRs and impairs reversal learning.

    PubMed

    Song, Woo Seok; Cha, Jin Hee; Yoon, Sang Ho; Cho, Young Seon; Park, Kyeong-Yeol; Kim, Myoung-Hwan

    2017-03-01

    Antipsychotic medication is an essential component for treating schizophrenia, which is a serious mental disorder that affects approximately 1% of the global population. Olanzapine (Olz), one of the most frequently prescribed atypical antipsychotics, is generally considered a first-line drug for treating schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive symptoms of schizophrenia are still unclear. In addition, the mechanisms by which Olz affects the neural circuits associated with cognitive function are unknown. Here we show that Olz interrupts depotentiation (reversal of long-term potentiation) without disturbing de novo LTP (long-term potentiation) and LTD (long-term depression). At hippocampal SC-CA1 synapses, inhibition of NMDARs (N-methyl-d-aspartate receptors), mGluRs (metabotropic glutamate receptors), or mAChRs (muscarinic acetylcholine receptors) disrupted depotentiation. In addition, co-activation of NMDARs, mGluRs, and mAChRs reversed stably expressed LTP. Olz inhibits the activation of mAChRs, which amplifies glutamate signaling through enhanced NMDAR opening and Gq (Gq class of G protein)-mediated signal transduction. Behaviorally, Olz impairs spatial reversal learning of mice in the Morris water maze test. Our results uncover a novel mechanism underpinning the cognitive modulation of Olz and show that the anticholinergic property of Olz affects glutamate signaling and synaptic plasticity.

  5. Enantioresolution of (RS)-baclofen by liquid chromatography: A review.

    PubMed

    Batra, Sonika; Bhushan, Ravi

    2017-01-01

    Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer for evaluation of the disposition of the racemic mixture of the drug. This calls for the development of enantioselective analytical methodology. This review summarizes and evaluates different methods of enantioseparation of (RS)-baclofen using both direct and indirect approaches, application of certain chiral reagents and chiral stationary phases (though very expensive). Methods of separation of diastereomers of (RS)-baclofen prepared with different chiral derivatizing reagents (under microwave irradiation at ease and in less time) on reversed-phase achiral columns or via a ligand exchange approach providing high-sensitivity detection by the relatively less expensive methods of TLC and HPLC are discussed. The methods may be helpful for determination of enantiomers in biological samples and in pharmaceutical formulations for control of enantiomeric purity and can be practiced both in analytical laboratories and industry for routine analysis and R&D activities.

  6. A Functional IL22 Polymorphism (rs2227473) Is Associated with Predisposition to Childhood Cerebral Malaria

    PubMed Central

    Marquet, Sandrine; Conte, Ianina; Poudiougou, Belco; Argiro, Laurent; Dessein, Hélia; Couturier, Charlène; Burté, Florence; Oumar, Aboubacar A.; Brown, Biobele J.; Traore, Abdoualye; Afolabi, Nathaniel K.; Barry, Abdoulaye; Omokhodion, Samuel; Shokunbi, Wuraola A.; Sodeinde, Olugbemiro; Doumbo, Ogobara; Fernandez-Reyes, Delmiro; Dessein, Alain J.

    2017-01-01

    Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali. Two SNPs of IL22, rs1012356 (P = 0.016, OR = 2.12) and rs2227476 (P = 0.007, OR = 2.08) were independently associated with CM in a sample of 115 Nigerian children with CM and 160 controls. The association with rs2227476 (P = 0.01) was replicated in 240 nuclear families with one affected child from Mali. SNP rs2227473, in linkage disequilibrium with rs2227476, was also associated with CM in the combined cohort for these two populations, (P = 0.004, OR = 1.55). SNP rs2227473 is located within a putative binding site for the aryl hydrocarbon receptor, a master regulator of IL-22 production. Individuals carrying the aggravating T allele of rs2227473 produced significantly more IL-22 than those without this allele. Overall, these findings suggest that IL-22 is involved in the pathogenesis of CM. PMID:28139719

  7. Effect of IAA produced by Klebsiella oxytoca Rs-5 on cotton growth under salt stress.

    PubMed

    Liu, Yan; Shi, Zaiqiang; Yao, Lixia; Yue, Haitao; Li, Hui; Li, Chun

    2013-01-01

    Klebsiella oxytoca Rs-5 isolated with ACC (1-aminocyclopropane-1-carboxylate) deaminase activity as the sole nitrogen source could obviously promote cotton seedling growth under salt stress and produce phytohormone indole-3-acetic acid (IAA). The amount of IAA produced by the strain Rs-5 was measured, and the effect of IAA on cotton growth under salt stress was studied. Different treatments were set to treat cotton seeds with fermentation broth containing strain Rs-5 (FB), strain Rs-5, fermentation broth with bacteria removed (FB-NB), fermentation broth without bacteria or IAA (FB-NB-NI) and single IAA solutions (SI) according to the IAA concentration after strain Rs-5 culturing of 48, 72 and 120 h. The germination rate, dry weight, plant height, root length and malondialdehyde (MDA), proline and endogenous IAA content in roots were determined. The results showed that both IAA produced by strain Rs-5 and the strain were effective in promoting cotton growth under salt stress. The growth and ability to resist salt stress of cotton seedlings were increased with the enhancement of IAA concentration. The treatment of FB containing bacteria and IAA at 120 h obtained the best state of cotton growth, when the IAA content was the highest in the fermentation broth (42.14 μg·L(-1)). The germination rate, dry weight, plant height and root length were increased by 29.4%, 24.3%, 27.2% and 27.2% , respectively, compared to the saline control. The strain Rs-5 and/or IAA could obviously reduce the MDA and proline content and increase the endogenous IAA content in cotton seedlings. However, the efficacy of other components in the fermentation broth was inconspicuous.

  8. High affinity group III mGluRs regulate mossy fiber input to CA3 interneurons.

    PubMed

    Cosgrove, Kathleen E; Meriney, Stephen D; Barrionuevo, Germán

    2011-12-01

    Stratum lacunosum-moleculare interneurons (L-Mi) in hippocampal area CA3 target the apical dendrite of pyramidal cells providing feedforward inhibition. Here we report that selective activation of group III metabotropic glutamate receptors (mGluRs) 4/8 with L(+)-2-amino-4-phosphnobytyric acid (L-AP4; 10 μM) decreased the probability of glutamate release from the mossy fiber (MF) terminals synapsing onto L-Mi. Consistent with this interpretation, application of L-AP4 in the presence of 3 mM strontium decreased the frequency of asynchronous MF EPSCs in L-Mi. Furthermore, the dose response curve showed that L-AP4 at 400 μM produced no further decrease in MF EPSC amplitude compared with 20 μM L-AP4, indicating the lack of mGluRs 7 at these MF terminals. We also found that one mechanism of mGluRs 4/8-mediated inhibition of release is linked to N-type voltage gated calcium channels at MF terminals. Application of the group III mGluR antagonist MSOP (100 μM) demonstrated that mGluRs 4/8 are neither tonically active nor activated by low and moderate frequencies of activity. However, trains of stimuli to the MF at 20 and 40 Hz delivered during the application of MSOP revealed a relief of inhibition of transmitter release and an increase in the overall probability of action potential firing in the postsynaptic L-Mi. Interestingly, the time to first action potential was significantly shorter in the presence of MSOP, indicating that mGluR 4/8 activation delays L-Mi firing in response to MF activity. Taken together, our data demonstrate that the timing and probability of action potentials in L-Mi evoked by MF synaptic input is regulated by the activation of presynaptic high affinity group III mGluRs.

  9. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    PubMed Central

    Ognjenović, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonović, Miljan

    2016-01-01

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. PMID:26869582

  10. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    DOE PAGES

    Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; ...

    2016-02-10

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

  11. The crystal structure of human GlnRS provides basis for the development of neurological disorders

    SciTech Connect

    Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; Baxa, Ulrich; Subramaniam, Sriram; Ling, Jiqiang; Simonovic, Miljan

    2016-02-10

    Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords

  12. Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients

    SciTech Connect

    Hitomi, Toshiaki; Habu, Toshiyuki; Kobayashi, Hatasu; Okuda, Hiroko; Harada, Kouji H.; Osafune, Kenji; Taura, Daisuke; Sone, Masakatsu; Asaka, Isao; Ameku, Tomonaga; Watanabe, Akira; Kasahara, Tomoko; Sudo, Tomomi; Shiota, Fumihiko; Hashikata, Hirokuni; Takagi, Yasushi; Morito, Daisuke; Miyamoto, Susumu; Nakao, Kazuwa; Koizumi, Akio

    2013-08-16

    Highlights: •Angiogenic activities were reduced in iPSECs from MMD patients. •Many mitosis-regulated genes were downregulated in iPSECs from MMD patients. •RNF213 R4810K downregulated Securin and inhibited angiogenic activity. •Securin suppression by siRNA reduced angiogenic activities of iPSECs and HUVECs. -- Abstract: Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. Induced pluripotent stem cells (iPSCs) were established from unaffected fibroblast donors with wild-type RNF213 alleles, and from carriers/patients with one or two RNF213 R4810K alleles. Angiogenic activities of iPSC-derived vascular endothelial cells (iPSECs) from patients and carriers were lower (49.0 ± 19.4%) than from wild-type subjects (p < 0.01). Gene expression profiles in iPSECs showed that Securin was down-regulated (p < 0.01) in carriers and patients. Overexpression of RNF213 R4810K downregulated Securin, inhibited angiogenic activity (36.0 ± 16.9%) and proliferation of humanumbilical vein endothelial cells (HUVECs) while overexpression of RNF213 wild type did not. Securin expression was downregulated using RNA interference techniques, which reduced the level of tube formation in iPSECs and HUVECs without inhibition of proliferation. RNF213 R4810K reduced angiogenic activities of iPSECs from patients with MMD, suggesting that it is a promising in vitro model for MMD.

  13. Association Study of Single Nucleotide Polymorphisms Rs4552569/Rs17095830 with Ankylosing Spondylitis in A Chinese Population

    PubMed Central

    Wang, Qingwen; Yang, Yuanyuan; Lv, Jiyang; Lin, Qi; Wang, Luo; Fanga, Zhengyu

    2016-01-01

    Genetics play a key role in ankylosing spondylitis (AS). A previous genome-wide association study (GWAS) showed that rs4552569 (on 5q14.3) and rs17095830 (on 12q12) were associated with the risk of AS in Han Chinese, which was not replicated in other two studies. In the current study, rs4552569 and rs17095830 were genotyped in 735 Han Chinese AS patients and 1204 healthy controls using high resolution melting analysis (HRMA). We compared the distributions of genotypes and alleles between AS cases and healthy controls. Rs30187 and rs10865331, which were reported to be associated with AS susceptibility in various populations, were also genotyped and analyzed as positive controls. The results showed that no association between rs4552569/rs17095830 polymorphisms and AS susceptibility was found. On the other hand, an association between rs17095830 and one of AS complication (inflammatory bowel disease) was observed (allelic P value=0.0180; odds ratio[OR]=1.739; 95% confidence interval [CI]=1.146-2.639). PMID:27047576

  14. Polymorphisms in Four Genes (KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963) and Their Correlation with Type 2 Diabetes Mellitus in Han Chinese in Henan Province, China.

    PubMed

    Gao, Kaiping; Wang, Jinjin; Li, Linlin; Zhai, Yujia; Ren, Yongcheng; You, Haifei; Wang, Bingyuan; Wu, Xuli; Li, Jianna; Liu, Zichen; Li, Xiong; Huang, Yaxin; Luo, Xin-Ping; Hu, Dongsheng; Ohno, Kinji; Wang, Chongjian

    2016-02-26

    Genetic variants at KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963 have been associated with type 2 diabetes mellitus (T2DM), but the results are contradictory in Chinese populations. The aim of the present study was to investigate the association of these four SNPs with T2DM in a large population of Han Chinese at Henan province, China. Seven-hundred-thirty-six patients with T2DM (cases) and Seven-hundred-sixty-eight healthy glucose-tolerant controls were genotyped for KCNQ1 rs151290, KLF14 rs972283, GCKR rs780094 and MTNR1B rs10830963. The association of genetic variants in these four genes with T2DM was analyzed using multivariate logistic regression. Genotypes and allele distributions of KCNQ1 rs151290 were significantly different between the cases and controls (p < 0.05). The AC and CC genotypes and the combined AC + CC genotype of rs151290 in KCNQ1 were associated with increases risk of T2DM before (OR = 1.482, 95% CI = 1.062-2.069; p = 0.021; OR = 1.544, 95% CI = 1.097-2.172, p = 0.013; and OR = 1.509, 95% CI = 1.097-2.077, p = 0.011, respectively) and after (OR = 1.539, 95% CI = 1.015-2.332, p = 0.042; OR = 1.641, 95% CI = 1.070-2.516, p = 0.023; and OR = 1.582, 95% CI = 1.061-2.358, p = 0.024; respectively) adjustment for sex, age, anthropometric measurements, biochemical indexes, smoking and alcohol consumption. Consistent with results of genotype analysis, the C allele of rs151290 in KCNQ1 was also associated with increased risk of T2DM (OR = 1.166, 95% CI = 1.004-1.355, p = 0.045). No associations between genetic variants of KLF14 rs972283, GCKR rs780094 or MTNR1B rs10830963 and T2DM were detected. The AC and CC genotypes and the C allele of rs151290 in KCNQ1 may be risk factors for T2DM in Han Chinese in Henan province.

  15. Molecular cloning of AtRS4, a seed specific multifunctional RFO synthase/galactosylhydrolase in Arabidopsis thaliana

    PubMed Central

    Gangl, Roman; Behmüller, Robert; Tenhaken, Raimund

    2015-01-01

    Stachyose is among the raffinose family oligosaccharides (RFOs) one of the major water-soluble carbohydrates next to sucrose in seeds of a number of plant species. Especially in leguminous seeds, e.g. chickpea, stachyose is reported as the major component. In contrast to their ambiguous potential as essential source of carbon for germination, RFOs are indigestible for humans and can contribute to diverse abdominal disorders. In the genome of Arabidopsis thaliana, six putative raffinose synthase genes are reported, whereas little is known about these putative raffinose synthases and their biochemical characteristics or their contribution to the RFO physiology in A. thaliana. In this paper, we report on the molecular cloning, functional expression in Escherichia coli and purification of recombinant AtRS4 from A. thaliana and the biochemical characterisation of the putative stachyose synthase (AtSTS, At4g01970) as a raffinose and high affinity stachyose synthase (Km for raffinose 259.2 ± 21.15 μM) as well as stachyose and galactinol specific galactosylhydrolase. A T-DNA insertional mutant in the AtRS4 gene was isolated. Only semi-quantitative PCR from WT siliques showed a specific transcriptional AtRS4 PCR product. Metabolite measurements in seeds of ΔAtRS4 mutant plants revealed a total loss of stachyose in ΔAtRS4 mutant seeds. We conclude that AtRS4 is the only stachyose synthase in the genome of A. thaliana that AtRS4 represents a key regulation mechanism in the RFO physiology of A. thaliana due to its multifunctional enzyme activity and that AtRS4 is possibly the second seed specific raffinose synthase beside AtRS5, which is responsible for Raf accumulation under abiotic stress. PMID:26483807

  16. Novel CC chemokine receptor 4 antagonist RS-1154 inhibits ovalbumin-induced ear swelling in mice.

    PubMed

    Nakagami, Yasuhiro; Kawashima, Kayo; Yonekubo, Kazuki; Etori, Maki; Jojima, Takaaki; Miyazaki, Shojiro; Sawamura, Ryoko; Hirahara, Kazuki; Nara, Futoshi; Yamashita, Makoto

    2009-12-10

    CC chemokine ligand 17 (CCL17/thymus and activation-regulated chemokine: TARC) and CCL22 (macrophage-derived chemokine: MDC) selectively bind to CC chemokine receptor 4 (CCR4). The CCR4 system is considered to be responsible for the pathology of allergic diseases such as atopic dermatitis. To find and develop potential medicines against allergic diseases, we screened an in-house library to search for compounds having a profile as a CCR4 antagonist. From among the screening hits, we focused on 3-{2-[(2R)-2-phenyl-4-(4-pyridin-4-ylbenzyl)morpholin-2-yl]ethyl}quinazoline-2,4(1H,3H)-dione (named RS-1154), which had been newly synthesized in our laboratory. This compound inhibited the binding of [(125)I]CCL17 to human CCR4-expressing CHO cells with an IC(50) value of 27.7 nM and moreover inhibited CCL17-induced migration of DO11.10 mice-derived T helper 2 cells with an IC(50) value of 1.5 nM in vitro. We then examined the effect of RS-1154 in an ovalbumin-induced ear swelling assay. The ear thickness was decreased by intravenous administration of anti-CCL17 or anti-CCL22 antibodies, suggesting that the CCR4 system is involved in the ear swelling. Though partially, the oral administration of RS-1154 also significantly ameliorated the ear swelling at the doses of 30 and 100 mg/kg. Furthermore, the serum level of interleukin-4 decreased after the administration of RS-1154. In this study, we succeeded in obtaining a newly-synthesized compound, RS-1154, which has a potential to inhibit the chemotaxis of T helper 2 cells in vitro and to ameliorate ovalbumin-induced ear swelling in vivo. These results raise the possibility that RS-1154 or one of derivatives might become a therapeutic agent for atopic dermatitis patients.

  17. Configuration control plan for the ports NCS IBM RS/6000

    SciTech Connect

    Brown, A.S.

    1996-07-01

    This document describes the actions and responsibilities for maintaining the quality and integrity of the NS software resident on the IBM RS/6000 workstation managed by the Nuclear Criticality Safety group at the Portsmouth Gaseous Diffusion Plant. This document does not address the validation of NS software packages for the RS/6000.

  18. Responding to the 5Rs: An Alternate Perspective of Slowmation

    ERIC Educational Resources Information Center

    Kidman, Gillian; Keast, Stephen; Cooper, Rebecca

    2012-01-01

    This paper is a response to Hoban and Neilsen's (2010) Five Rs model for understanding how learners engage with slowmation. An alternative model (the Learning MMAEPER Model) that builds on the 5Rs model is explained in terms of its use in secondary science preservice teacher education. To probe into the surface and deep learning that can occur…

  19. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  20. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  1. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS). 103.1...

  2. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  3. 10 CFR 434.103 - Referenced standards (RS).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Referenced standards (RS). 434.103 Section 434.103 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Administration and Enforcement-General § 434.103 Referenced standards (RS)....

  4. [Improvement of natamycin production in an industrial strain by heterologous expression of the afsRS(cla) global regulatory genes].

    PubMed

    Tao, Zhengsheng; Wang, Yemin; Zheng, Hualiang; Tao, Meifeng

    2015-05-01

    The afsRS(cla) global regulatory genes from Streptomyces clavuligerus activate the production of two antibiotics in Streptomyces lividans. In this study, we gained an increase of 38% in the production of natamycin (3.56 g/L) in an industrial strain Streptomyces gilvosporeus TZ1401 through the integration of pHL851 that bears the afsRS(cla) global regulatory genes into its genome. We discovered by quantitive real-time reverse transcription PCR (qRT-PCR) that the expression of 6 genes of the natamycin biosynthetic gene cluster were improved from 1.9 to 2.7 times. This suggests that afsRS(cla) improve the production of natamycin through increased transcription. This study provides a good example for applying afsRS(cla) in high yield breeding of industrial antibiotic producers.

  5. MBOAT7 rs641738 increases risk of liver inflammation and transition to fibrosis in chronic hepatitis C

    PubMed Central

    Thabet, Khaled; Asimakopoulos, Anastasia; Shojaei, Maryam; Romero-Gomez, Manuel; Mangia, Alessandra; Irving, William L.; Berg, Thomas; Dore, Gregory J.; Grønbæk, Henning; Sheridan, David; Abate, Maria Lorena; Bugianesi, Elisabetta; Weltman, Martin; Mollison, Lindsay; Cheng, Wendy; Riordan, Stephen; Fischer, Janett; Spengler, Ulrich; Nattermann, Jacob; Wahid, Ahmed; Rojas, Angela; White, Rose; Douglas, Mark W.; McLeod, Duncan; Powell, Elizabeth; Liddle, Christopher; van der Poorten, David; George, Jacob; Eslam, Mohammed; Gallego-Duran, Rocio; Applegate, Tanya; Bassendine, Margaret; Rosso, Chiara; Mezzabotta, Lavinia; Leung, Reynold; Malik, Barbara; Matthews, Gail; Grebely, Jason; Fragomeli, Vincenzo; Jonsson, Julie R.; Santaro, Rosanna

    2016-01-01

    Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis. PMID:27630043

  6. High pressure intensification of cassava resistant starch (RS3) yields.

    PubMed

    Lertwanawatana, Proyphon; Frazier, Richard A; Niranjan, Keshavan

    2015-08-15

    Cassava starch, typically, has resistant starch type 3 (RS3) content of 2.4%. This paper shows that the RS3 yields can be substantially enhanced by debranching cassava starch using pullulanase followed by high pressure or cyclic high-pressure annealing. RS3 yield of 41.3% was obtained when annealing was carried out at 400MPa/60°C for 15 min, whereas it took nearly 8h to obtain the same yield under conventional atmospheric annealing at 60°C. The yield of RS3 could be further significantly increased by annealing under 400 MPa/60°C pressure for 15 min followed by resting at atmospheric pressure for 3h 45 min, and repeating this cycle for up to six times. Microstructural surface analysis of the product under a scanning electron microscope showed an increasingly rigid density of the crystalline structure formed, confirming higher RS3 content.

  7. Religiosity/spirituality of German doctors in private practice and likelihood of addressing R/S issues with patients.

    PubMed

    Voltmer, Edgar; Bussing, Arndt; Koenig, Harold G; Al Zaben, Faten

    2014-12-01

    This study examined the self-assessed religiosity and spirituality (R/S) of a representative sample of German physicians in private practice (n = 414) and how this related to their addressing R/S issues with patients. The majority of physicians (49.3 %)reported a Protestant denomination, with the remainder indicating mainly either Catholic(12.5 %) or none (31.9 %). A significant proportion perceived themselves as either religious(42.8 %) or spiritual (29.0 %). Women were more likely to rate themselves R/S than did men. Women (compared to men) were also somewhat more likely to attend religious services (7.4 vs. 2.1 % at least once a week) and participate in private religious activities(14.9 vs. 13.7 % at least daily), although these differences were not statistically significant.The majority of physicians (67.2 %) never/seldom addressed R/S issues with a typical patient. Physicians with higher self-perceived R/S and more frequent public and private religious activity were much more likely to address R/S issues with patients. Implications for patient care and future research are discussed.

  8. Arterial and venous vasodilator actions of RS-1893, a novel cardiotonic agent, in the hindlimb preparation of the dog.

    PubMed

    Miyake, S; Shiga, H; Koike, H

    1989-10-01

    RS-1893, an orally active cardiotonic agent, has been suggested to dilate venous blood vessels, because it markedly decreases central venous pressure in anesthetized dogs. In order to evaluate venous vasodilator action of the agent, we measured hindlimb volume (HLV) in anesthetized dogs using a plethysmographic technique. RS-1893 (1-10 micrograms/kg, i.v.) produced dose-dependent increases in HLV, femoral blood flow, and left ventricular (LV)dP/dt, and a decrease in central venous pressure (CVP). In another series of experiments, we autoperfused the hindlimb with a constant flow and injected the drugs intraarterially (i.a.) to separately evaluate arterial and venous vasodilator actions. In this preparation, a decrease in perfusion pressure and an increase in HLV were considered to reflect arterial vasodilatation and venous vasodilatation, respectively. RS-1893 (0.3-3 micrograms i.a.) produced a dose-dependent increase in HLV and a decrease in perfusion pressure. Comparison of doses which increased HLV by 0.3 ml revealed that RS-1893 was about 20 times more potent than milrinone. The arterial vasodilator action of RS-1893 was about 15 times more potent than that of milrinone. We conclude that RS-1893 is a potent venous and arterial vasodilator with cardiotonic activity.

  9. SWP Echelle Spectra of Chromospherically Active Dwarf Stars

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    High resolution spectra of the 1150-2000 A region are enormously valuable for probing outer- atmosphere structure in cool stars. For example, such data can be used to separate blends, identify individual emission components in short-period binary systems, determine intensity ratios in close multiplets, estimate reliable emission strengths of lines superimposed on bright stellar continua, and test for the presence or absence of stellar winds at 105 K temperatures. These possibilities are not practical with IUE low-dispersion spectra. However, one must pay a steep-price to obtain useable high-dispersion IUE spectra and the additional dimension of diagnostic information, namely only a handful of the brightest UV sources are accessible even with shift-long exposures. We propose below an observing program to obtain echelle spectra of chromospherically active dwarf stars in the 1150-2000 A shortwavelength region. This program is intended to explore a particular class of objects that heretofore have not been observed at high dispersion with the SWP camera. Futhermore, this program complements previous SWP echelle studies by our group at the University of Colorado of quiet-chromosphere dwarf stars (alpha Cen A, alpha Cen B), active giants (alpha Aur A, lambda And, beta Dra), and the extreme case of the very active RS CVn-type system HR 1099. As described below, highdispersion spectra of these targets have provided a critical interpretive dimension that was lacking in previous low-dispersion studies. However, several fundamental questions have been raised in the course of our exploratory SWP work on what, in practice, are two distinct classes of chromospheric stars: the quiet dwarfs and the active giants. We feel that many of these questions can be answered by bridging the interpretive gap with a careful study of the active dwarfs. Our recent experience with shift-long SWP echelle exposures of chromospheric emission stars has suggested that our previous estimates of

  10. Leukocyte Telomere Length-Related rs621559 and rs398652 Genetic Variants Influence Risk of HBV-Related Hepatocellular Carcinoma

    PubMed Central

    Shi, Juan; Lu, Chao; Wei, Jinyu; Li, Lichao; Zhou, Changchun; Yuan, Qipeng; Zhou, Liqing; Yang, Ming

    2014-01-01

    Recent genome-wide association studies (GWAS) have identified eleven leukocyte telomere length (LTL)-related single nucleotide polymorphisms (SNPs). Since LTL has been associated with risk of many malignancies, LTL-related SNPs may contribute to cancer susceptibility. To test this hypothesis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we genotyped these eleven LTL-related SNPs in a case-control set including 1186 HBV-related HCC cases, 508 chronic HBV carriers and 1308 healthy controls at the discovery stage. The associations of HCC risk with these SNPs were further confirmed in an independent case-control set. We found that 1p34.2 rs621559 and 14q21 rs398652 were significantly associated with HBV-related HCC risk (both P<0.005 after Bonferroni corrections). There was no significant difference of either rs621559 or rs398652 genotypes between chronic HBV carriers and healthy controls, demonstrating that the association was not due to predisposition to HBV infection. In the pooled analyses (1806 HBV-related HCC cases and 1954 controls), we observed a decreased HCC risk, 0.72-times, associated with the 1p34.2 rs621559 AA genotype compared to the GG genotype (P = 1.6×10−6). Additionally, there was an increased HCC risk, 1.27-fold, associated with the rs398652 GG genotype (P = 3.3×10−6). A statistical joint effect between the rs621559 GG and rs398652 GG genotypes may exist in elevating risk of HBV-related HCC. We show, for the first time, that rs398652 and rs621559 might be marker genetic variants for risk of HBV-related HCC in the Chinese population. PMID:25365256

  11. Association between RAD 51 rs1801320 and susceptibility to glioblastoma.

    PubMed

    Franceschi, S; Tomei, S; Mazzanti, C M; Lessi, F; Aretini, P; La Ferla, M; De Gregorio, V; Pasqualetti, F; Zavaglia, K; Bevilacqua, G; Naccarato, A G

    2016-01-01

    Glioblastoma is the most common and aggressive malignant primary brain tumor. Despite decades of research and the advent of new therapies, patients with glioblastoma continue to have a very poor prognosis. Radiation therapy has a major role as adjuvant treatment for glioblastoma following surgical resection. Many studies have shown that polymorphisms of genes involved in pathways of DNA repair may affect the sensitivity of the cells to treatment. Although the role of these polymorphisms has been investigated in relation to response to radiotherapy, their role as predisposing factors to glioblastoma has not been clarified yet. In the present study, we evaluated the association between polymorphisms in DNA repair genes, namely: XRCC1 rs25487, XRCC3 rs861539 and RAD51 rs1801320, with the susceptibility to develop glioblastoma. Eighty-five glioblastoma patients and 70 matched controls were recruited for this study. Data from the 1000 Genomes Project (98 Tuscans) were also downloaded and used for the association analysis. Subjects carrying RAD51 rs1801320 GC genotype showed an increased risk of glioblastoma (GC vs GG, χ(2) = 10.75; OR 3.0087; p = 0.0010). The C allele was also significantly associated to glioblastoma (χ(2) = 8.66; OR 2.5674; p = 0.0032). Moreover, RAD51 rs1801320 C allele increased the risk to develop glioblastoma also when combined to XRCC1 rs25487 G allele and XRCC3 rs861539 C allele (χ(2) = 6.558; p = 0.0053).

  12. CollAborative care and active surveillance for Screen-Positive EldeRs with subthreshold depression (CASPER): a multicentred randomised controlled trial of clinical effectiveness and cost-effectiveness.

    PubMed Central

    Lewis, Helen; Adamson, Joy; Atherton, Katie; Bailey, Della; Birtwistle, Jacqueline; Bosanquet, Katharine; Clare, Emily; Delgadillo, Jaime; Ekers, David; Foster, Deborah; Gabe, Rhian; Gascoyne, Samantha; Haley, Lesley; Hargate, Rebecca; Hewitt, Catherine; Holmes, John; Keding, Ada; Lilley-Kelly, Amanda; Maya, Jahnese; McMillan, Dean; Meer, Shaista; Meredith, Jodi; Mitchell, Natasha; Nutbrown, Sarah; Overend, Karen; Pasterfield, Madeline; Richards, David; Spilsbury, Karen; Torgerson, David; Traviss-Turner, Gemma; Trépel, Dominic; Woodhouse, Rebecca; Ziegler, Friederike; Gilbody, Simon

    2017-01-01

    BACKGROUND Efforts to reduce the burden of illness and personal suffering associated with depression in older adults have focused on those with more severe depressive syndromes. Less attention has been paid to those with mild disorders/subthreshold depression, but these patients also suffer significant impairments in their quality of life and level of functioning. There is currently no clear evidence-based guidance regarding treatment for this patient group. OBJECTIVES To establish the clinical effectiveness and cost-effectiveness of a low-intensity intervention of collaborative care for primary care older adults who screened positive for subthreshold depression. DESIGN A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. SETTING Thirty-two general practitioner (GP) practices in the north of England. PARTICIPANTS A total of 705 participants aged ≥ 75 years during the pilot phase and ≥ 65 years during the main trial with subthreshold depression. INTERVENTIONS Participants in the intervention group received a low-intensity intervention of collaborative care, which included behavioural activation delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual GP care. Control-arm participants received only usual GP care. MAIN OUTCOME MEASURES The primary outcome measure was a self-reported measure of depression severity, the Patient Health Questionnaire-9 items PHQ-9 score at 4 months post randomisation. Secondary outcome measures included the European Quality of Life-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder seven-item scale, Connor-Davidson Resilience Scale two-item version, a medication questionnaire and objective data. Participants were followed up for 12 months. RESULTS In total, 705

  13. Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock

    PubMed Central

    Cardoso, Cristina Padre; de Oliveira, Argenil José de Assis; Botoni, Fernando Antônio; Rezende, Isabela Cristina Porto; Alves-Filho, Jose Carlos; Cunha, Fernando de Queiroz; Estanislau, Juliana de Assis Silva Gomes; Magno, Luiz Alexandre Viana; Rios-Santos, Fabricio

    2015-01-01

    Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock. PMID:26038959

  14. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Kos, Larry; Burnside, Christopher G.; Bruno, Cy

    2013-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program, specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. MSFC is working closely with the USAF to obtain RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. As originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single boost. For both the small

  15. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Kos, Larry; Bruno, Cy

    2012-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the decommissioned United States Air Force Peacekeeper ICBM program; specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC is working closely with the USAF to obtain all the remaining RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single

  16. BRDT gene sequence in human testicular pathologies and the implication of its single nucleotide polymorphism (rs3088232) on fertility.

    PubMed

    Barda, S; Yogev, L; Paz, G; Yavetz, H; Lehavi, O; Hauser, R; Doniger, T; Breitbart, H; Kleiman, S E

    2014-07-01

    Bromodomain testis-specific (BRDT) protein is essential for the normal process of spermatogenesis. Mutant mice that expressed truncated BRDT had impaired testicular histology with severely reduced sperm concentration and abnormal sperm morphology, while a model of knockout Brdt mice with no BRDT protein had complete meiotic arrest. A BRDT single nucleotide polymorphism (SNP) (rs3088232) was reported as being associated with infertility in men. We assessed testicular specimens of 276 azoospermic men who underwent testicular sperm extraction to search for specimens that showed spermatogenic impairments similar to those of mutant BRDT mice. Ten similar specimens were selected for BRDT gene sequencing and they revealed three NCBI-reported SNPs (rs10783071, rs3088232 and rs10747493) variously distributed among them. Bioinformatics analysis predicted that they would not affect protein activity. Further assessment of rs3088232 frequency in a large group of non-obstructive azoospermia men and fertile controls demonstrated no significant difference between them (27.2 and 21.7% respectively; p = 0.122, Fisher's exact test). We conclude that the testicular impairments observed in the 10 specimens were not a consequence of BRDT gene mutation. The association between BRDT rs3088232 and infertility that had been reported in other studies was not supported.

  17. The Role of CzcRS Two-Component Systems in the Heavy Metal Resistance of Pseudomonas putida X4

    PubMed Central

    Liu, Pulin; Chen, Xi; Huang, Qiaoyun; Chen, Wenli

    2015-01-01

    The role of different czcRS genes in metal resistance and the cross-link between czcRS and czcCBA in Pseudomonas putida X4 were studied to advance understanding of the mechanisms by which P. putida copes with metal stress. Similar to P. putida KT2440, two complete czcRS1 and czcRS2 two-component systems, as well as a czcR3 without the corresponding sensing component were amplified in P. putida X4. The histidine kinase genes czcS1 and czcS2 were inactivated and fused to lacZ by homologous recombination. The lacZ fusion assay revealed that Cd2+ and Zn2+ caused a decrease in the transcription of czcRS1, whereas Cd2+ treatment enhanced the transcription of czcRS2. The mutation of different czcRSs showed that all czcRSs are necessary to facilitate full metal resistance in P. putida X4. A putative gene just downstream of czcR3 is related to metal ion resistance, and its transcription was activated by Zn2+. Data from quantitative real-time polymerase chain reaction (qRT-PCR) strongly suggested that czcRSs regulate the expression of czcCBA, and a cross-link exists between different czcRSs. PMID:26225958

  18. 5-HTTLPR/rs25531 polymorphism and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus.

    PubMed

    Kruschwitz, J D; Walter, M; Varikuti, D; Jensen, J; Plichta, M M; Haddad, L; Grimm, O; Mohnke, S; Pöhland, L; Schott, B; Wold, A; Mühleisen, T W; Heinz, A; Erk, S; Romanczuk-Seiferth, N; Witt, S H; Nöthen, M M; Rietschel, M; Meyer-Lindenberg, A; Walter, H

    2015-07-01

    The s/s-genotype of the 5-HTTLPR polymorphism and the personality trait of neuroticism have both been associated with experiences of negative affect, anxiety and mood disorders, as well as an emotional processing bias towards negative facial emotions. On a neural level, this bias can be characterized by altered amygdala and fusiform gyrus (FFG) activity during perception of negative facial expressions. Using resting-state functional magnetic resonance imaging in a multi-center-sample of 178 healthy subjects of European descent, this study investigated the association of 5-HTTLPR (short s- and long l-allele) including the genotype of the single nucleotide polymorphism (SNP) rs25531 (A/G) within this region polymorphism, and trait neuroticism on resting-state functional connectivity (rs-FC) between amygdala and the FFG. Moreover, we aimed to identify additional brain regions with associations of 5-HTTLPR/rs25531 (combined according to its expression; low: s/s; high: l(A)/l(A); intermediate: s/l(A), s/l(G), l(G)/l(G), l(A)/l(G)) and trait neuroticism to amygdala rs-FC. Separate analyses for 5-HTTLPR/rs25531 and neuroticism (controlling for age, gender, handedness, and research site) revealed that s/s-homozygotes and individuals high in neuroticism obtained altered amygdala rs-FC in the right occipital face area, which is considered to be a "core component" of the face processing system. Importantly, effects of neuroticism were replicated across three independent research sites. Additionally, associations of 5-HTTLPR/rs25531 genotype and amygdala rs-FC were observed in the anterior and posterior cingulate cortex, whereas neuroticism was not related to rs-FC in these areas. The presented data implies that 5-HTTLPR/rs25531 variants and neuroticism are linked by resting state functional connectivity of amygdala and fusiform gyrus and suggests that variants of 5-HTTLPR/rs25531 genotype and different levels of neuroticism may partly account for altered processing of

  19. Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population

    PubMed Central

    Wang, Xi-Jing; Kang, Hua-Feng; Jin, Tian-Bo; Zhang, Shu-Qun; Guan, Hai-Tao; Yang, Peng-Tao; Liu, Kang; Liu, Xing-Han; Xu, Peng; Zheng, Yi; Dai, Zhi-Jun

    2017-01-01

    Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.   PMID:28228606

  20. Association of Renalase SNPs rs2296545 and rs2576178 with the Risk of Hypertension: A Meta-Analysis

    PubMed Central

    Ma, Wang-Ge; Yan, Ding-Yi; Zheng, Wen-Ling; Chu, Chao; Guo, Tong-Shuai; Yuan, Zu-Yi; Mu, Jian-Jun

    2016-01-01

    Background/Aims Two renalase single nucleotide polymorphisms (SNPs) rs2296545 and rs2576178 have been reported to be associated with the susceptibility to hypertension (HT). Given the inconsistent results, we conducted a meta-analysis to assess the association between these two SNPs and the risk of HT. Methods Electronic databases were systematically searched to find relevant studies. Subgroup analysis was conducted according to the different concomitant diseases and ethnicities in the study population. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using fixed-effect or random-effect models. Results A total of six case–control studies on rs2296545 and six studies on rs2576178 were included. In the combined analysis, results showed a significant association between SNP rs2296545 and risk of HT in all genetic models (dominant model CG+CC/GG: OR = 1.43, 95% CI = 1.24–1.65; recessive model CC/CG+GG: OR = 1.36, 95% CI = 1.09–1.69; codominant model CC/GG: OR = 1.63, 95% CI = 1.20–2.20, CG/GG: OR = 1.30, 95% CI = 1.12–1.52; allelic model C/G: OR = 1.29, 95% CI = 1.10–1.51). In subgroup analysis, we observed a significant association between rs2296545 and risk of essential HT. Although we did not observe an association between rs2576178 polymorphism and HT in the combined analysis, an increased risk was observed in the essential HT patients versus healthy controls (subgroup 1) analysis under the dominant, recessive, and codominant genetic models. Conclusions Renalase gene rs2296545 polymorphism is significantly associated with increased risk of HT, whereas rs2576178 polymorphism may not be associated with the susceptibility to HT. PMID:27434211

  1. Association between miR-199a rs74723057 and MET rs1621 polymorphisms and the risk of hepatocellular carcinoma

    PubMed Central

    Li, Qiang; Qin, Linyuan; Tan, Shengkui; Zeng, Xiaoyun; Qiu, Xiaoqiang; Tang, Bo; Jin, Junfei; Liao, Weijia; Qiu, Moqin; Tan, Lijun; He, Gaofeng; Li, Xiaomei; He, Songqing; Yu, Hongping

    2016-01-01

    MicroRNAs (miRNAs) can regulate gene expression at post-transcriptional levels, thereby influence cancer risk. The aim of the current study is to investigate association between miR-199a rs74723057 and MET rs1621 and HCC risk in 1032 HCC patients and 1060 cancer-free controls. These two SNPs were genotyped by using the Agena MassARRAY genotyping system. Odds ratio (OR) and 95% confidence interval (95%CI) were calculated to assess the strength of the associations. We found that compared with the wild-type AA genotype of MET rs1621, the variant GG genotype was associated with a decreased risk for HCC (OR = 0.24, 95% CI = 0.06–0.96, P = 0.043). No association between miR-199a rs74723057 and HCC risk was observed. In addition, an interaction effect on HCC risk between the selected two SNPs was found. Among those who carried the CG/GG genotypes of miR-199a rs74723057, those who carried the GG genotype of MET rs1621 had a reduced risk of HCC, when compared with those who carried the AG/AA genotypes of MET rs1621 (OR = 0.15, 95% CI = 0.03~0.73, P for interaction = 0.018). Our results suggest that MET rs1621 polymorphism, alone and combined with miR-199a rs74723057, may influence susceptibility to HCC. Further large-scale association studies and functional studies are needed to validate our findings. PMID:27813498

  2. Relationship Between Chronic Tinnitus and Glial Cell Line-Derived Neurotrophic Factor Gene rs3812047, rs1110149, and rs884344 Polymorphisms in a Turkish Population.

    PubMed

    Orenay-Boyacioglu, Seda; Coskunoglu, Aysun; Caki, Zerrin; Cam, Fethi Sirri

    2016-08-01

    Glial cell line-derived neurotrophic factor (GDNF) plays a key role in early development of central auditory pathway and the inner ear. However, the auditory pathway studies of GDNF gene polymorphisms are scarce in the literature, and the studies especially associated with tinnitus are limited. Our study aimed to identify whether GDNF gene polymorphisms play any roles in the pathophysiology of tinnitus by investigating the relationship between tinnitus and GDNF polymorphisms. A total of 52 patients with chronic tinnitus and ages ranging from 18 to 55 were admitted to the Ear-Nose-Throat outpatient clinic of Celal Bayar University Medical Faculty Hospital of Manisa, Turkey and constituted the study group. Another 42 patients of the same age range, without tinnitus symptoms and lacking any systemic disease, were also admitted to the clinic and formed the control group. The tympanometric, audiological, and psychoacoustic assessments of the subjects were performed. Deoxyribonucleic acid samples obtained using venous blood taken for routine inspections were used to investigate GDNF gene polymorphisms (rs884344, rs3812047, and rs1110149) by polymerase chain reaction-based restriction fragment length polymorphism method. No correlation could be detected between GDNF rs884344 and rs3812047 polymorphisms and subjects with tinnitus (p > 0.05). Heterozygosity was significantly lower for GDNF rs1110149 polymorphism in tinnitus subjects compared to the controls (p < 0.05). However, the allele frequencies for all 3 polymorphisms were not significantly different between tinnitus and control groups (p > 0.05). Failure to detect correlations between tinnitus and GDNF gene polymorphisms suggests this may be due to the fact that the GDNF gene has a variable expression pattern in different tissues and pathologies. Therefore, the study should be improved and its scope should be expanded by including a larger group of patients and different tissues to investigate the expression

  3. AirMSPI SEAC4RS Ellipsoid Data

    Atmospheric Science Data Center

    2017-03-16

    ... AirMSPI SEAC4RS Ellipsoid-projected Georegistered Radiance Data AirMSPI Ellipsoid-Projected Georegistered Radiance Product ... Polarized Radiance DOLP AOLP Order Data:  Earthdata Search:  Earthdata Search SCAR-B ...

  4. AirMSPI SEAC4RS Terrain Data

    Atmospheric Science Data Center

    2017-03-16

    ... AirMSPI SEAC4RS Terrain-projected Georegistered Radiance Data AirMSPI Terrain-Projected Georegistered Radiance Product ... Polarized Radiance DOLP AOLP Order Data:  Earthdata Search:  Earthdata Search Read ...

  5. Regional Science and Technology (RS&T) Organizations

    EPA Pesticide Factsheets

    EPA’s RS&T Organizations perform analytical and other work that: practices sound science, implements the principles of environmental protection, and promotes partnerships with states, Indian Nations, and local governments.

  6. Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population

    PubMed Central

    Chandra, Vishal; Kim, Jong Joo; Gupta, Usha; Mittal, Balraj; Rai, Rajani

    2016-01-01

    Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p ≤ 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p ≤ 0.0001; AA vs. GG + GA; OR = 1.52, p ≤ 0.004, A vs. G allele: OR = 1.41, p ≤ 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p ≤ 0.0001; CT + TT vs. CC: OR = 1.24, p ≤ 0.0001; TT vs. CC + CT; OR = 1.17, p ≤ 0.005, T vs. C allele: OR = 1.16, p ≤ 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk. PMID:26891331

  7. Exosomal miRs in Lung Cancer: A Mathematical Model

    PubMed Central

    Lai, Xiulan; Friedman, Avner

    2016-01-01

    Lung cancer, primarily non-small-cell lung cancer (NSCLC), is the leading cause of cancer deaths in the United States and worldwide. While early detection significantly improves five-year survival, there are no reliable diagnostic tools for early detection. Several exosomal microRNAs (miRs) are overexpressed in NSCLC, and have been suggested as potential biomarkers for early detection. The present paper develops a mathematical model for early stage of NSCLC with emphasis on the role of the three highest overexpressed miRs, namely miR-21, miR-205 and miR-155. Simulations of the model provide quantitative relationships between the tumor volume and the total mass of each of the above miRs in the tumor. Because of the positive correlation between these miRs in the tumor tissue and in the blood, the results of the paper may be viewed as a first step toward establishing a combination of miRs 21, 205, 155 and possibly other miRs as serum biomarkers for early detection of NSCLC. PMID:28002496

  8. Determination of RS,E/Z-tocotrienols by HPLC.

    PubMed

    Drotleff, A M; Ternes, W

    2001-02-16

    Synthetic alpha-tocotrienol was separated into four geometrical E/Z side chain isomers by preparative HPLC (permethylated beta-cyclodextrin phase). The isolated isomers were resolved in ethylene glycol dimethyl ether, converted into the corresponding methyl ether using dimethyl sulfate, and the tocotrienol methyl ethers were extracted with n-hexane. A subsequent HPLC separation on a chiral phase (adsorbent cellulose derivated with 3,5-dimethyl phenyl carbamate) discriminates between the enantiomers of each E/Z side chain isomer, achieving the complete resolution of the eight occurring synthetic RS,E/Z-alpha-tocotrienols. The method can be shortened by omitting the preparative separation of the E/Z tocotrienol isomers prior to the chromatography on the chiral dimethyl phenyl carbamate phase. The simplified method achieved the following separation: RS,E/Z-alpha-tocotrienol separated into five peaks, RS,E/Z-beta-tocotrienol into eight, RS,E/Z-gamma-tocotrienol into six and RS,E/Z-delta-tocotrienol into eight peaks. The naturally occurring R,E-E-tocotrienol isomer could be identified within the synthetic RS,E/Z-isomers by co-chromatography with tocotrienol methyl ethers derived from natural sources, respectively.

  9. RASSF1A and the rs2073498 Cancer Associated SNP

    PubMed Central

    Donninger, Howard; Barnoud, Thibaut; Nelson, Nick; Kassler, Suzanna; Clark, Jennifer; Cummins, Timothy D.; Powell, David W.; Nyante, Sarah; Millikan, Robert C.; Clark, Geoffrey J.

    2011-01-01

    RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also complex with the Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 29% of European populations [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing breast cancer. We have used a proteomics based approach to identify multiple differences in the pattern of protein/protein interactions mediated by the wild type compared to the SNP variant protein. We have also identified a significant difference in biological activity between wild type and SNP variant protein. However, we have found only a very modest association of the SNP with breast cancer predisposition. PMID:22649770

  10. Correction: Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock.

    PubMed

    2015-11-01

    Vol. 110 (4): 453-460, 2015. p. 453. "Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock" should read: "Interleukin-10 rs1800896 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock". == Vol. 110 (6): 797-800, 2015 .p. 797. "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5)" should read: "Financial support: IOC/FIOCRUZ, PAPESIV/VPPDT/FIOCRUZ, FAPERJ-APQ1 (E-26/110.497/2011), CNPq (458858/2014-5),FAPEAM/CNPq/PPP-FAPEAM (010/2011), MCT/CNPq (014/2011)"

  11. A multiwavelength campaign of active stars with intermediate rotation rates

    NASA Technical Reports Server (NTRS)

    Dempsey, Robert C.; Neff, James E.; ONeal, Douglas; Olah, Katalin

    1995-01-01

    Near-to-simultaneous ultraviolet and visual spectroscopy of two moderate nu(sin i) RS CVn systems, V815 Herculis (nu(sin i) = 27 km s(exp -1)) and LM Pegasi (nu(sin i) = 24 km s(exp -1)), are presented along with contemporaneous UBV (RI)(sub c) - band photometry. These data were used to probe inhomogeneities in the chromospheres and photospheres, and the possible relationship between them. Both systems show evidence for rotationally modulated chromospheric emission, generally varying in antiphase to the photospheric brightness. A weak flare was observed at Mg II for V815 Her. In the case of IM Peg, we use photometry and spectra to estimate temperatures, sizes, and locations of photospheric spots. Further constraints on the spot temperature is provided by TiO observations. For IM Peg, the anticorrelation between chromospheric emission and brightness is discussed in the context of a possible solar-like spot cycle.

  12. Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor)

    PubMed Central

    Lagmay, Joanne P.; London, Wendy B.; Gross, Thomas G.; Termuhlen, Amanda; Sullivan, Nicholas; Axel, Amy; Mundy, Bethany; Ranalli, Mark; Canner, Jason; McGrady, Patrick; Hall, Brett

    2009-01-01

    Purpose Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression. Experimental design DNA samples from 96 high risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor (IL-6R), rs1800795 and rs8192284 respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was performed to determine SNP-related event free survival (EFS) and overall survival (OS) rates. Results The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in -high risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value. Conclusions The rs1800795 SNP (-174 IL-6 (G>C) represents a novel and independent prognostic marker for both EFS and OS in high risk neuroblastoma. Since the rs1800795 SNP (-174 IL-6 (G>C) has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma. PMID:19671870

  13. NEURL rs6584555 and CAND2 rs4642101 contribute to postoperative atrial fibrillation: a prospective study among Chinese population

    PubMed Central

    Liu, Chong; Shen, Jiayi; Huang, Ying

    2016-01-01

    Postoperative atrial fibrillation (POAF) is a serious, common complication after coronary artery bypass grafting (CABG) surgery. Recently, 5 novel loci were identified to be associated with atrial fibrillation susceptibility using a combination of genotyping, eQTL mapping, and functional validation. In current study, we aim to evaluated the positive findings for POAF susceptibility after CABG among Chinese population, using a population-based, two-stage, nested case-control study with 1,400 patients. NEURL rs12415501 and CAND2 rs4642101 were significantly associated with POAF susceptibility after CABG among Chinese population in both stages. When pooled together, the ORs for each additional copy of minor allele was 1.29 (95% CI: 1.13-1.48, P = 1.7×10−4) for NEURL rs12415501, and 1.21 (95% CI: 1.08-1.36, P = 9.8×10−4) for CAND2 rs4642101. Functional validation experiments found the AF risk allele of NEURL rs6584555 and CAND2 rs4642101 correlated with an increased expression of its corresponding genes (P<0.001). In this independently collected cardiac surgery cohort, we replicated the previous findings, and 2 novel loci are independently associated with POAF risk in patients who undergo CABG surgery in Chinese population. PMID:27203392

  14. Association between IL-1α rs17561 and IL-1β rs1143634 polymorphisms and periodontitis: a meta-analysis.

    PubMed

    Yin, W T; Pan, Y P; Lin, L

    2016-02-05

    Genetic variations in human interleukin-1 (IL-1) genes are known to be involved in inflammatory disorders. The rs17561 and rs1143634 polymorphisms of IL-1α and IL-1β, respectively, have been increasingly recognized as important regulators in the development of periodontitis. However, the existence of a specific association remains controversial. Therefore, we performed a meta-analysis to explore the relationship between IL-1 polymorphism and periodontitis risk. Based on our inclusion criteria, six case-control studies were used, involving a total of 336 periodontitis cases and 366 healthy controls. Our meta-analysis results showed that the T allele of IL-1α rs17561 is positively associated with periodontitis susceptibility. In addition, carriers of this allele (TC + TT genotypes) demonstrated increased risk of this disease. The IL-1β rs1143634 T allele was also positively connected to periodontitis, with TC + TT genotype carriers being significantly more at risk. These results demonstrate that the IL-1α rs17561 and IL-1β rs1143634 polymorphisms are associated with periodontitis.

  15. CREM variants rs4934540 and rs2295415 conferred susceptibility to nonobstructive azoospermia risk in the Chinese population.

    PubMed

    He, Xiao-Jin; Song, Bing; Du, Wei-Dong; Cao, Yun-Xia; Zhang, Yan; Ruan, Jian; Tian, Hui; Zhou, Fu-Sheng; Zuo, Xian-Bo; Wu, Huan; Zha, Xing; Xie, Xu-Shi; Wei, Zhao-Lian; Zhou, Ping

    2014-08-01

    To evaluate the association of variants related to spermatogenesis with susceptibility to Chinese idiopathic nonobstructive azoospermia (NOA), seventeen tag single-nucleotide polymorphisms (SNPs) in CREM, ACT, KIF17b, and SPAG8 were analyzed in 361 NOA patients and 368 controls by Sequenom iplex technology. The results showed that two CREM SNPs, rs4934540 and rs22954152, were significantly associated with NOA and played protective roles against the disease (P value with Bonferroni correction = 0.00017, odds ratio [OR] = 0.624 and P = 0.012, OR = 0.686, respectively). Haplotype analysis of CREM gene variants suggested that haplotype CGTG of the SNPs, rs4934540, rs2295415, rs11592356, and rs1148247, exhibited significant protective effect against the occurrence of NOA (P = 0.001, OR = 0.659). The haplotype TATG conferred a significantly increased risk of NOA (P = 0.011, OR = 1.317). Furthermore, making use of quantitative RT-PCR, we demonstrated that relative mRNA expression of CREM in NOA patients with maturation arrest was only one-third of that in the controls with normal spermatogenesis (P < 0.0001). Our findings indicated that the polymorphisms of CREM gene were associated with NOA in the Chinese population and low CREM expression might be involved in the pathogenesis of spermatogenesis maturation arrest.

  16. Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease in patients with rheumatoid arthritis.

    PubMed

    García-Bermúdez, Mercedes; López-Mejías, Raquel; González-Juanatey, Carlos; Castañeda, Santos; Miranda-Filloy, José A; Blanco, Ricardo; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; González-Alvaro, Isidoro; Gómez-Vaquero, Carmen; Llorca, Javier; Martín, Javier; González-Gay, Miguel A

    2012-07-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates the innate immune response via NF-kB pathway and mitogen-activated protein kinase signaling, leading to expression of proinflammatory cytokines and chemokines. The G allele of TLR4 rs4986790 (+896A>G, Asp299Gly) gene polymorphism has been implicated in reduction of risk of atherosclerosis. In this study, 1481 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were genotyped for the rs4986790 TLR4 variant to determine the influence of this variant in the risk of CV events in these patients. Also, HLA-DRB1 status was determined using molecular based methods. Moreover, potential influence of rs4986790 variant in the development of subclinical atherosclerosis was assessed in a subgroup of RA patients with no history of CV events by the measurement of surrogate markers of subclinical atherosclerosis. No statistically significant differences in allele or genotype frequencies for the rs4986790 variant between RA patients who experienced CV events or not were found. Likewise, no significant association between this gene variant and any of the surrogate markers of subclinical atherosclerosis was found. In summary, results in our study do not support the hypothesis that the rs4986790 (+896A>G, Asp299Gly) TLR4 variant may influence predisposition for subclinical atherosclerosis and clinically evident CV disease in RA patients.

  17. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide

    NASA Astrophysics Data System (ADS)

    Hoobakht, Fatemeh; Ganji, Fariba; Vasheghani-Farahani, Ebrahim; Mousavi, Seyyed Mohammad

    2013-09-01

    Pyridostigmine bromide (PB) is an inhibitor of cholinesterase, which is used in the treatment of myasthenia gravis and administered for protection against exposure to toxic nerve agents. Tests were done to investigate prolonging the half-life of PB and improving its release behavior. PB was loaded in nanoparticles (NPs) of Eudragit RS PO (Eu-RS) prepared using the technique of quasi emulsion solvent diffusion. Variables of output power of the sonicator, bath temperature and mixing time, were chosen as the optimization factors to obtain the minimum sized NPs. In addition, emulsions were tested at different ratios of drug-to-polymer by dynamic light scattering to determine size and zeta potential of NPs. UV-spectroscopy was used to determine PB content of the NPs. Drug-loaded NPs were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectra. Results determined that mixing time had a significant impact on the size of Eu-RS NPs, but power output of sonicator and bath temperature had no significant effect. The particle size obtained at the optimum condition (power output of 70 W, bath temperature of 33 °C, and mixing time of 7 min) was less than 200 nm (optimum sizes were 138.9 and 179.5 nm for Eu-RS and PB-loaded Eu-RS NPs, respectively). The optimum PB-loaded Eu-RS NPs at the PB to Eu-RS weight ratio of 1-4 and 20 % of loaded PB released from the nanocarriers within 100 h.

  18. Inactivation of a Two-Component Signal Transduction System, SaeRS, Eliminates Adherence and Attenuates Virulence of Staphylococcus aureus

    PubMed Central

    Liang, Xudong; Yu, Chuanxin; Sun, Junsong; Liu, Hong; Landwehr, Christina; Holmes, David; Ji, Yinduo

    2006-01-01

    Staphylococcus aureus is a major human and animal pathogen. During infection, this organism not only is able to attach to and enter host cells by using its cell surface-associated factors but also exports toxins to induce apoptosis and kill invaded cells. In this study, we identified the regulon of a two-component signal transduction system, SaeRS, and demonstrated that the SaeRS system is required for S. aureus to cause infection both in vitro and in vivo. Using microarray and real-time reverse transcriptase PCR analyses, we found that SaeRS regulates the expression of genes involved in adhesion and invasion (such as those encoding fibronectin-binding proteins and fibrinogen-binding proteins) and genes encoding α-, β-, and γ-hemolysins. Surprisingly, we found that SaeRS represses the Agr regulatory system since the mutation of saeS up-regulates agrA expression, which was confirmed by using an agr promoter-reporter fusion system. More importantly, we demonstrated that inactivation of the SaeRS system significantly decreases the bacterium-induced apoptosis and/or death of lung epithelial cells (A549) and attenuates virulence in a murine infection model. Moreover, we found that inactivation of the SaeRS system eliminates staphylococcal adhesion and internalization of lung epithelial cells. We also found that both a novel hypothetical protein (the SA1000 protein) and a bifunctional protein (Efb), which binds to extracellular fibrinogen and complement factor C3, might partially contribute to bacterial adhesion to and invasion of epithelial cells. Our results indicate that activation of the SaeRS system may be required for S. aureus to adhere to and invade epithelial cells. PMID:16861653

  19. Modification of heparanase gene expression in response to conditioning and LPS treatment: strong correlation to rs4693608 SNP.

    PubMed

    Ostrovsky, Olga; Shimoni, Avichai; Baryakh, Polina; Morgulis, Yan; Mayorov, Margarita; Beider, Katia; Shteingauz, Anna; Ilan, Neta; Vlodavsky, Israel; Nagler, Arnon

    2014-04-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of HSPGs, important structural and functional components of the ECM. Cleavage of HS leads to loss of the structural integrity of the ECM and release of HS-bound cytokines, chemokines, and bioactive angiogenic- and growth-promoting factors. Our previous study revealed a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing GVHD. We now demonstrate that HPSE is up-regulated in response to pretransplantation conditioning, followed by a gradual decrease thereafter. Expression of heparanase correlated with the rs4693608 HPSE SNP before and after conditioning. Moreover, a positive correlation was found between recipient and donor rs4693608 SNP discrepancy and the time of neutrophil and platelet recovery. Similarly, the discrepancy in rs4693608 HPSE SNP between recipients and donors was found to be a more significant factor for the risk of aGVHD than patient genotype. The rs4693608 SNP also affected HPSE gene expression in LPS-treated MNCs from PB and CB. Possessors of the AA genotype exhibited up-regulation of heparanase with a high ratio in the LPS-treated MNCs, whereas individuals with genotype GG showed down-regulation or no effect on HPSE gene expression. HPSE up-regulation was mediated by TLR4. The study emphasizes the importance of rs4693608 SNP for HPSE gene expression in activated MNCs, indicating a role in allogeneic stem cell transplantation, including postconditioning, engraftment, and GVHD.

  20. ABCG1 rs57137919G>A Polymorphism Is Functionally Associated with Varying Gene Expression and Apoptosis of Macrophages

    PubMed Central

    Liu, Fang; Wang, Wei; Xu, Yan; Wang, Yu; Chen, Lian-Feng; Fang, Quan; Yan, Xiao-Wei

    2014-01-01

    ATP-binding cassette transporter G1 (ABCG1) is a transmembrane cholesterol transporter involved in macrophage sterol homeostasis, reverse cholesterol transport (RCT), and atherosclerosis. The role of ABCG1 in atherosclerosis remains controversial, especially in animal models. Our previous study showed that single nucleotide polymorphism rs57137919 (-367G>A) in the ABCG1 promoter region was associated with reduced risk for atherosclerotic coronary artery disease (CAD). This study was designed to provide functional evidence for the role of rs57137919G>A in atherosclerosis in humans. We combined in vitro and ex vivo studies using cell lines and human monocyte-derived macrophages to investigate the functional consequences of the promoter polymorphism by observing the effects of the rs57137919A allele on promoter activity, transcription factor binding, gene expression, cholesterol efflux, and apoptosis levels. The results showed that the rs57137919A allele was significantly associated with decreased ABCG1 gene expression possibly due to the impaired ability of protein-DNA binding. ABCG1-mediated cholesterol efflux decreased by 23% with rs57137919 A/A versus the G/G genotype. Cholesterol-loaded macrophage apoptosis was induced 2-fold with the A/A genotype compared with the G/G genotype. Proapoptotic genes Bok and Bid mRNA levels were significantly increased in macrophages from the A/A genotype compared with those from the G/G genotype. These findings demonstrated that the ABCG1 promoter rs57137919G>A variant had an allele-specific effect on ABCG1 expression and was associated with an increased apoptosis in cholesterol-loaded macrophages, providing functional evidence to explain the reduced risk for atherosclerosis in subjects with the ABCG1 promoter rs57137919A allele as reported in our previous study. PMID:24972087

  1. Asymmetric photolysis of /RS/-leucine with circularly polarized ultraviolet light

    NASA Technical Reports Server (NTRS)

    Flores, J. J.; Bonner, W. A.; Massey, G. A.

    1977-01-01

    (RS)-leucine in 0.1 M HCl solution has been subjected to photolysis with 212.8-nm right (R-) and left circularly polarized light (LCPL) obtained from a laser source. RCPL preferentially photolyzed the (R)-leucine component and LCPL the (S)-leucine component of the RS substrate. The enantiomeric excess produced were 1.98% for the 59% conversion with RCPL and 2.50% for the 75% conversion with LCPL. These 'equal and opposite' effects represent the second highest enantiomeric enrichments yet reported for an asymmetric photolysis and the first ever reported for a prebiotically important substrate - an amino acid. Implications regarding the origin of optical activity are briefly discussed.

  2. PepO, a CovRS-controlled endopeptidase, disrupts Streptococcus pyogenes quorum sensing

    PubMed Central

    Wilkening, Reid V.; Chang, Jennifer C.; Federle, Michael J.

    2016-01-01

    Summary Group A Streptococcus (GAS, Streptococcus pyogenes) is a human-restricted pathogen with a capacity to both colonize asymptomatically and cause illnesses ranging from pharyngitis to necrotizing fasciitis. An understanding of how and when GAS switches between genetic programs governing these different lifestyles has remained an enduring mystery and likely requires carefully tuned environmental sensors to activate and silence genetic schemes when appropriate. Herein, we describe the relationship between the Control of Virulence (CovRS, CsrRS) two-component system and the Rgg2/3 quorum-sensing pathway. We demonstrate that responses of CovRS to the stress signals Mg2+ and a fragment of the antimicrobial peptide LL-37 result in modulated activity of pheromone signaling of the Rgg2/3 pathway through a means of proteolysis of SHP peptide pheromones. This degradation is mediated by the cytoplasmic endopeptidase PepO, which is the first identified enzymatic silencer of an RRNPP-type quorum-sensing pathway. These results suggest that under conditions in which the virulence potential of GAS is elevated (i.e. enhanced virulence gene expression), cellular responses mediated by the Rgg2/3 pathway are abrogated and allow individuals to escape from group behavior. These results also indicate that Rgg2/3 signaling is instead functional during non-virulent GAS lifestyles. PMID:26418177

  3. Metric Rocketry and the Three Rs.

    ERIC Educational Resources Information Center

    Walter, Frank W.

    1982-01-01

    Described is a unit on rockets which begins with watching a film and ends with teams of students launching their own rockets. Activities teach students metric measuring, data collecting and graphing, report writing, and calculating, as well as group skills and model building skills. (DC)

  4. The New Three Rs: Reduce, Reuse, & Recycle!

    ERIC Educational Resources Information Center

    Virginia State Dept. of Waste Management, Richmond. Div. of Litter & Recycling.

    Given the growing interest in the environment and the mounting crisis in solid waste management, many secondary teachers have been seeking curriculum materials which can help them address these issues with their classes. This document is a collection of 12 multidisciplinary activities which are offered to assist in the education of these students.…

  5. Assessment of IL-28: rs12979860 and rs8099917 Polymorphisms in a Cohort of Cuban Chronic HCV Genotype 1b Patients

    PubMed Central

    Palenzuela Gardón, Daniel; Guillen, Isabel Alicia; Fernández, Julio R.; Camacho, Hamlet; Estevez, Zurina Cinza; Dueñas, Santiago; Alvares-Lajonchere, Liz; Amador, Yalena; Martinez-Donato, Gillian; Han, Junsong; Zhang, Zhiming; Zhang, Xiaona; Gao, Yang; Campaña, Juan Roca; Novoa, Lidia I.

    2016-01-01

    Hepatitis C virus (HCV) is a significant global public health problem with >185 million infections worldwide. A series of genome-wide association studies (GWAS) has identified IL-28B polymorphisms as a predictor of sustained virologic response (SVR), as well as spontaneous clearance in chronic HCV genotype 1 patients. The objective of this work was to evaluate the prevalence of IL-28B rs12979860 and rs8099917 polymorphisms in Cuban chronic HCV patients. The study cohort included 73 chronic HCV patients treated with concomitant administration of CIGB-230 and nonpegylated IFN-α plus ribavirin (non-pegIFN-α/R) antiviral therapy. The genotype distribution of IL-28B rs12979860CC, -CT, and -TT was 29, 41, and 30%, respectively, and the distribution for rs8099917TT, -TG, and -GG was 63, 31, and 5%, respectively. The allele frequencies for rs12979860C and -T alleles were 51 and 49%, respectively, and for rs8099917G and -T alleles, the values were 21 and 79%, respectively. SVR rates were 55, 42, and 35% for rs12979860CC, -CT, and -TT, respectively, and 52, 30, and 25% for rs8099917TT, -GT, and -GG, respectively. The combined assessment of both single nucleotide polymorphisms (SNPs) resulted in 3 major genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TT, and rs12979860CT/rs8099917GG) with a frequency of 30.1, 21.9, and 20.5%, respectively. In patients with heterozygous variant rs12979860CT, the additional genotyping of rs8099917 contributed to increase the SVR rate. It is concluded that in Cuban HCV-infected patients, the responder homogeneous variant rs8099917TT is the most frequent genotype. The simultaneous genotyping of 2 IL-28B SNPs could improve the prediction of SVR contributing to better therapeutic decisions and treatment management. PMID:28058039

  6. Association of Peroxisome Proliferator-Activated Receptor α/δ/γ With Obesity, and Gene–Gene Interaction, in the Chinese Han Population

    PubMed Central

    Luo, Wenshu; Guo, Zhirong; Wu, Ming; Hao, Chao; Hu, Xiaoshu; Zhou, Zhengyuan; Zhou, Zhiwu; Yao, Xingjuan; Zhang, Lijun; Liu, Jingchao

    2013-01-01

    Background We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARs) with obesity and the additional role of gene–gene interaction. Methods Participants were recruited within the framework of the Prevention of Multiple Metabolic Disorders and MS in Jiangsu Province cohort population survey of an urban community in China. In total, 820 subjects (513 nonobese adults, 307 obese adults) were randomly selected, and no individuals were consanguineous. Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806, and rs4684847) were genotyped and analyzed. Results After covariate adjustment, minor alleles of rs2016520 in PPARδ and rs10865170 in PPARγ were associated with lower BMI (P < 0.01 for all). Generalized multifactor dimensionality reduction analysis showed significant gene–gene interaction among rs2016520, rs9794, and rs10865170 in 3-dimensional models (P = 0.0010); prediction accuracy was 0.6011 and cross-validation consistency was 9/10. It also showed significant gene–gene interaction between rs2016520 and rs10865170 in all 2-dimensional models (P = 0.0010); prediction accuracy was 0.6072 and cross-validation consistency was 9/10. Conclusions rs2016520 and rs10865170 were associated with lower obesity risk. In addition, interaction was identified among rs2016520, rs9794, and rs10865170 in obesity. PMID:23545576

  7. Genetic Association of CHAT rs3810950 and rs2177369 Polymorphisms with the Risk of Alzheimer's Disease: A Meta-Analysis.

    PubMed

    Liu, Yong; Chen, Qicong; Liu, Xu; Dou, Mengmeng; Li, Silu; Zhou, Jiahui; Liu, Hong; Wu, Yongfu; Huang, Zunnan

    2016-01-01

    Choline acetyltransferase (CHAT) rs3810950 and rs2177369 polymorphisms have been implicated in susceptibility to Alzheimer's disease (AD). Due to the inconsistent results from previous studies, a meta-analysis was performed to estimate the association between these polymorphisms and AD risk more precisely. Pooled results of our meta-analysis indicated CHAT rs2177369 polymorphism was correlated with decreasing AD risk in one of five genetic models (dominant: OR = 0.77, 95% CI: 0.62-0.96), while rs3810950 mutant was associated with AD development in three models (allelic: OR = 1.18, 95% CI: 1.01-1.37, homozygous: OR = 1.63, 95% CI: 1.09-2.42, and recessive: OR = 1.65, 95% CI: 1.20-2.26). In subgroup analysis by ethnicity, the association between CHAT rs3810950 polymorphism and AD risk was just found in the recessive model (OR = 1.47, 95% CI: 1.05-2.07) among Caucasians, while four genetic models (allelic: OR = 1.23, 95% CI: 1.01-1.48; homozygous: OR = 2.24, 95% CI: 1.48-3.39; dominant: OR = 1.21, 95% CI: 1.06-1.40; and recessive: OR = 2.18, 95% CI: 1.45-3.29) assumed this association in Asians. In conclusion, our meta-analysis indicated CHAT rs2177369 polymorphism might play a protective role in AD, while rs3810950 variant was a risk factor for AD but its single heterozygous mutations might not influence susceptibility to AD.

  8. NeurimmiRs: microRNAs in the neuroimmune interface.

    PubMed

    Soreq, Hermona; Wolf, Yochai

    2011-10-01

    Recent reports of microRNA (miR) modulators of both neuronal and immune processes (here termed NeurimmiRs) predict therapeutic potential for manipulating NeurimmiR levels in diseases affecting both the immune system and higher brain functions, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and anxiety-related disorders. In our opinion, NeurimmiRs that function within both the nervous and the immune systems, such as miR-132 and miR-124, may act as 'negotiators' between these two interacting compartments. We suggest that NeurimmiRs primarily target transcriptional or other regulatory genes, which enables modulation of both immune and cognitive processes through direct or indirect alterations of neuron-glia and/or brain-to-body signaling. Thus, manipulating NeurimmiR control over the immune contributions to cognitive pathways may offer new therapeutic targets.

  9. Interleukin-28B rs12979860 C allele: Protective against advanced fibrosis in chronic hepatitis C genotype 1 infection.

    PubMed

    Kitson, Matthew T; George, Jacob; Dore, Gregory J; Leung, Reynold; Button, Peter; McCaughan, Geoffrey W; Grawford, Darrell H G; Siebert, William; Weltman, Martin D; Cheng, Wendy S C; Roberts, Stuart K

    2014-01-01

    Background and Aim: While genetic polymorphisms upstream of the interleukin-28B(IL28B) gene are associated with necroinflammatory activity grade in chronic hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is less definitive. Pretreatment liver biopsies in a cohort of treatment-naïve patients with HCV-1 were analyzed to evaluate associations between liver histology, and the rs12979860 and rs8099917 IL28B single nucleotide polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high activity grade (A2/3) were identified using multivariable logistic regression analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141 patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P = 0.03), with an increasing number of Talleles associated with a higher frequency of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97–0.99; P < 0.0001), high activity grade (OR 5.68, 95% CI% 1.86–17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36, 95% CI 0.14–0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00–1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be independently associated with a lower prevalence of advanced fibrosis stage in HCV-1 infection. This association warrants further evaluation.

  10. Polymorphisms rs12998 and rs5780218 in KiSS1 Suppressor Metastasis Gene in Mexican Patients with Breast Cancer

    PubMed Central

    Cruz Quevedo, Edhit Guadalupe; Mimendi Aguilar, Gabriela Monserrat; Juárez Aguilar, Luis Anselmo; Gutierrez Rubio, Susan Andrea; Flores Martínez, Silvia Esperanza; Dávalos Rodríguez, Ingrid Patricia; Sánchez Corona, José; Torres Morán, Martha Isabel; Rosales Gómez, Roberto Carlos; Morán Moguel, María Cristina

    2015-01-01

    Aims. KiSS1 is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along the KiSS-1 gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K) KiSS1 polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC). Results. The rs5780218 polymorphism was individually associated with breast cancer (P = 0.0332) and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared (P < 0.0001). The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674). Conclusions. Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) in KiSS1 gene must be analyzed in other populations. PMID:25810563

  11. Restoring New Agegraphic Dark Energy in RS II Braneworld

    NASA Astrophysics Data System (ADS)

    Jamil, Mubasher; Karami, K.; Sheykhi, A.

    2011-10-01

    Motivated by recent works (Saridakis in Phys. Lett. B 660:138, 2008; Sheykhi in Int. J. Mod. Phys. D 19(3):305, 2010), we investigate the new agegraphic model of dark energy in the framework of RS II braneworld. We also include the case of variable gravitational constant G in our model. Moreover, we reconstruct the potential and the dynamics of the quintessence, tachyon, K-essence and dilaton scalar field models according to the evolutionary behavior of the new agegraphic dark energy model in RS II braneworld cosmology including varying G.

  12. MMP-9 gene polymorphisms (rs3918242, rs3918254 and rs4810482) and the risk of psoriasis vulgaris: No evidence for associations in a Chinese Han population.

    PubMed

    Liang, Jingyao; Zhao, Tian; Yang, Juan; Li, Wei; Zhang, Fang; Zhang, Sanquan; Huang, Zhenming; Lin, Rihua; Zhang, Xibao

    2015-12-01

    Several previous studies including one of them co-authored by our group have revealed that serum and psoriatic plaque expression of matrix metalloproteinase-9 (MMP-9) was significantly upregulated in psoriasis. The aim of this study was to investigate the association of three single nucleotide polymorphisms (SNPs) and haplotypes of MMP-9 (rs3918242, rs3918254 and rs4810482) with psoriasis vulgaris in a Chinese Han population. The serum levels of MMP-9 in 245 psoriasis vulgaris cases and 256 healthy controls were assessed using ELSA kits, and the three SNPs were genotyped using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Four haplotypes based on the three SNPs were also analyzed. Our study showed that the serum MMP-9 levels in patients with psoriasis vulgaris were significantly higher than that in controls (P<0.05). However, the three SNPs were not significantly associated with psoriasis vulgaris susceptibility (all P>0.05). Similar results were found in further subgroup analysis based on gender, age of onset, family history, and serum MMP-9 levels, except that a protective effect of psoriasis vulgaris was detected among female subjects with the CT genotype of rs3918254 (OR=0.47, 95% CI=0.23-0.96, P=0.038), but this association did not survive after Bonferroni correction (P(adj)=0.076). The haplotype analysis also failed to show any association with psoriasis vulgaris. We found no evidence for the association between the MMP-9 polymorphisms and psoriasis vulgaris susceptibility in a Chinese Han population.

  13. The CARD9 Polymorphisms rs4077515, rs10870077 and rs10781499 Are Uncoupled from Susceptibility to and Severity of Pulmonary Tuberculosis

    PubMed Central

    Iannaconne, Marco; McEwen, Gayle; Ciontea, Marius Sorin; Olaru, Marian; Capparelli, Rosanna; Ioana, Mihai; Kaufmann, Stefan H. E.; Dorhoi, Anca

    2016-01-01

    Genetic variants in the CARD9 gene predispose to inflammatory disorders and chronic infectious diseases. Tuberculosis (TB), a chronic infectious disease affecting the lung, is lethal in Card9-deficient mice. We hypothesized that polymorphisms in the CARD9 gene influence TB progression and disease-associated lung damage in humans. We tested genotype distributions of the CARD9 polymorphisms rs4077515, rs10781499 and rs10870077 in TB patients and healthy subjects in a Caucasian cohort. SNPs were in linkage disequilibrium and none of the haplotypes was significantly enriched in the TB group. We determined total and differential leukocyte count, erythrocyte sedimentation rate and plasma abundance of cytokines and chemokines as markers for systemic inflammation and scored chest X-rays to assess lung involvement in TB subjects. Most disease parameters segregated independently of the CARD9 haplotypes. In contrast to multifactorial chronic inflammation, selected genetic variants in the CARD9 gene leave host responses apparently unaffected in TB, at least in the population analyzed here. PMID:27684065

  14. (R,S)-2-chlorophenoxyl pyrazolides as novel substrates for improving lipase-catalyzed hydrolytic resolution.

    PubMed

    Kao, Min-fang; Lu, Pei-yu; Kao, Jou-yan; Wang, Pei-yun; Wu, An-chi; Tsai, Shau-Wei

    2012-01-01

    The best reaction condition of Candida antartica lipase B as biocatalyst, 3-(2-pyridyl)pyrazole as leaving azole, and water-saturated methyl t-butyl ether as reaction medium at 45°C were first selected for performing the hydrolytic resolution of (R,S)-2-(4-chlorophenoxyl) azolides (1-4). In comparison with the kinetic resolution of (R,S)-2-phenylpropionyl 3-(2-pyridyl)pyrazolide or (R,S)-α-methoxyphenylacetyl 3-(2-pyridyl)pyrazolide at the same reaction condition, excellent enantioselectivity with more than two order-of-magnitudes higher activity for each enantiomer was obtained. The resolution was then extended to other (R,S)-3-(2-pyridyl)pyrazolides (5-7) containing 2-chloro, 3-chloro, or 2,4-dichloro substituent, giving good (E > 48) to excellent (E > 100) enantioselectivity. The thermodynamic analysis for 1, 2, and 4-7 demonstrates profound effects of the acyl or leaving moiety on varying enthalpic and entropic contributions to the difference of Gibbs free energies. A thorough kinetic analysis further indicates that on the basis of 6, the excellent enantiomeric ratio for 4 and 7 is due to the higher reactivity of (S)-4 and lower reactivity of (R)-7, respectively.

  15. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.

    PubMed

    Guo, Min; Chong, Yeeting E; Shapiro, Ryan; Beebe, Kirk; Yang, Xiang-Lei; Schimmel, Paul

    2009-12-10

    Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.

  16. mGluRs modulate strength and timing of excitatory transmission in hippocampal area CA3.

    PubMed

    Cosgrove, Kathleen E; Galván, Emilio J; Barrionuevo, Germán; Meriney, Stephen D

    2011-08-01

    Excitatory transmission within hippocampal area CA3 stems from three major glutamatergic pathways: the perforant path formed by axons of layer II stellate cells in the entorhinal cortex, the mossy fiber axons originating from the dentate gyrus granule cells, and the recurrent axon collaterals of CA3 pyramidal cells. The synaptic communication of each of these pathways is modulated by metabotropic glutamate receptors that fine-tune the signal by affecting both the timing and strength of the connection. Within area CA3 of the hippocampus, group I mGluRs (mGluR1 and mGluR5) are expressed postsynaptically, whereas group II (mGluR2 and mGluR3) and III mGluRs (mGluR4, mGluR7, and mGluR8) are expressed presynaptically. Receptors from each group have been demonstrated to be required for different forms of pre- and postsynaptic long-term plasticity and also have been implicated in regulating short-term plasticity. A recent observation has demonstrated that a presynaptically expressed mGluR can affect the timing of action potentials elicited in the postsynaptic target. Interestingly, mGluRs can be distributed in a target-specific manner, such that synaptic input from one presynaptic neuron can be modulated by different receptors at each of its postsynaptic targets. Consequently, mGluRs provide a mechanism for synaptic specialization of glutamatergic transmission in the hippocampus. This review will highlight the variability in mGluR modulation of excitatory transmission within area CA3 with an emphasis on how these receptors contribute to the strength and timing of network activity within pyramidal cells and interneurons.

  17. A Role for σRs in Stimulant Self-administration and Addiction

    PubMed Central

    Katz, Jonathan L.; Hong, Weimin C.; Hiranita, Takato; Su, Tsung-Ping

    2015-01-01

    Sigma-1 receptors (σ1Rs) are structurally unique intracellular proteins that function as chaperones. σ1Rs translocate from the mitochondria-associated membrane to other sub-cellular compartments, and can influence a host of targets, including ion channels, G-protein-coupled receptors, lipids, and other signaling proteins. Drugs binding to σRs can induce or block the actions of σRs. Studies indicate that stimulant self-administration induces reinforcing effects of σR agonists, due to dopamine transporter actions. Once established the reinforcing effects of σR agonists are independent of dopaminergic mechanisms traditionally thought to be critical in the reinforcing effects of stimulants. Self-administered doses of σR agonists do not increase dopamine concentrations in the nucleus accumbens shell, a transmitter and brain region considered important for reinforcing effects of abused drugs. However, the self-administration of σR agonists is blocked by σR antagonists. Several effects of stimulants have been blocked by σR antagonists, including reinforcing effects assessed by a place-conditioning procedure. However, the self-administration of stimulants is largely unaffected by σR antagonists, indicating fundamental differences in the mechanisms underlying these two procedures used to assess reinforcing effects. When σR antagonists are administered in combination with dopamine uptake inhibitors an effective and specific blockade of stimulant self-administration is obtained. Actions of stimulant drugs related to their abuse induce unique changes in σR activity and the changes induced potentially create redundant, and once established, independent reinforcement pathways. Concomitant targeting of both dopaminergic pathways and σR proteins produces a selective antagonism of stimulant self-administration, suggesting new avenues for combination chemotherapies to specifically combat stimulant abuse. PMID:26650253

  18. Association of Versican (VCAN) gene polymorphisms rs251124 and rs2287926 (G428D), with intracranial aneurysm

    PubMed Central

    Sathyan, Sanish; Koshy, Linda V.; Balan, Shabeesh; Easwer, H.V.; Premkumar, S.; Nair, Suresh; Bhattacharya, R.N.; Alapatt, Jacob P.; Banerjee, Moinak

    2014-01-01

    Intracranial aneurysm (IA) accounts for 85% of Subarachnoid Hemorrhage (SAH) and is mainly caused due to the weakening of arterial wall. The structural integrity of the intracranial arteries is mainly influenced by the extracellular matrix (ECM) remodeling. The Proteoglycan Versican plays an important role in extracellular matrix assembly and plays a major role in the pathogenesis of IA. The linkage studies also indicated VCAN as a putative candidate gene for IA in the 5q22–31 region. Using a case–control study design, we tested the hypothesis whether the variants in VCAN gene, nonsynonymous variants in the coding region of Glycosaminoglycan α (GAG-α) and GAG-β and two reported SNPs involved in splicing rs251124 and rs173686 can increase the risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We selected 200 radiologically confirmed aneurysmal cases and 250 ethnically, age and sex matched controls from the Dravidian Malayalam speaking population of South India. The present study reiterated the earlier association of rs251124 with intracranial aneurysm (P = 0.0002) and also found a novel association with rs2287926 (G428D) in exon 7 coding for GAG-α with intracranial aneurysm (P = 0.0015). Interestingly, both these SNPs contributed to higher risk for aneurysm in males. In-silico analysis predicted this SNP to have the highest functional relevance in the gene which might have a potentially altered regulatory role in transcription and splicing. Using meta-analysis with available literature rs251124 was found to be the strongest intracranial aneurysm marker for global ethnicities. This study with a novel functional SNP rs2287926 (G428D) further substantiates the potential role of VCAN in the pathogenesis of IA. PMID:25606449

  19. The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate cancer risk.

    PubMed

    Fu, Chenying; Dong, Wen-Qi; Wang, Ani; Qiu, Guozhen

    2014-08-01

    Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2 rs1256049 polymorphisms to explore associations with prostate cancer risk. These studies showed inconsistent and conflicting results. The aim of this meta-analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms with prostate cancer risk. A systematic literature search was conducted to identify related studies (up to February 2014) in several online databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A total of 16 eligible articles were enrolled in this updated meta-analysis. The result suggested that ESR1 rs9340799 polymorphism was significantly associated with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707). The cumulative meta-analysis and sensitivity analysis showed the results were robust. In conclusion, this meta-analysis indicated that ESR1 rs9340799 polymorphism was associated with prostate cancer risk in overall populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was associated with prostate cancer risk in Caucasians. However, the biological mechanisms need to be further investigated.

  20. Sirtuin 1 rs1467568 and rs7895833 in South African Indians with early-onset coronary artery disease

    PubMed Central

    Ramkaran, Prithiksha; Moodley, Devapregasan; Chuturgoon, Anil A; Phulukdaree, Alisa; Khan, Sajidah

    2016-01-01

    Summary Background Sirtuin 1 (SIRT1), a class III histone deacetylase, has been identified as a candidate molecule affecting the epigenetic mechanisms of cardiovascular disease (CVD). Previous studies have shown that some SIRT1 single-nucleotide polymorphisms (SNPs) are associated with body mass index, diabetes, blood pressure, cholesterol metabolism and coronary artery calcification. We investigated two A>G SIRT1 SNPs, rs1467568 and rs7895833, in young South African (SA) Indians with coronary artery disease (CAD) and compared them to Indian and black controls. Methods For rs1467568, a total of 287 subjects were recruited into this study (104 CAD patients, 99 age-, gender- and race-matched controls, and 84 age- and gender-matched black controls). For rs7895833, a total of 281 subjects were recruited into this study (100 CAD patients, 99 age-, gender- and race-matched controls, and 82 age- and gender-matched black controls). All patients were male, of Indian ethnicity, stable CAD confirmed on angiography, mean age 37.5 years; range 24–45. All subjects were genotyped using TaqMan SNP genotyping assays. Results The variant allele for both SNPs was found at a higher frequency in the total Indian group compared to the total black population (rs1467568: 41 vs 18.5%, respectively, p < 0.0001, OR = 3.190, 95% CI: 2.058–40943; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.466, 95% CI: 1.620– 3.755). Indian controls presented with a higher frequency for both SNPs compared to black controls (rs1467568: 40 vs 18.5%, respectively, p < 0.0001, OR = 2.996, 95% CI: 1.850– 4.853; and rs7895833: 41 vs 22%, respectively, p < 0.0001, OR = 2.513, 95% CI: 1.578–4.004). No difference was seen in the distribution of both SNPs between CAD patients and either control group. We did not observe any association between the SNPs and clinical parameters in CAD patients and controls. Conclusion: Both SNP variant alleles occurred more frequently in SA Indians than in SA

  1. A Functional Polymorphism (rs10817938) in the XPA Promoter Region Is Associated with Poor Prognosis of Oral Squamous Cell Carcinoma in a Chinese Han Population

    PubMed Central

    Gao, Chunhai; Wang, Jinzhu; Li, Chong; Zhang, Wei; Liu, Guoxia

    2016-01-01

    Single nucleotide polymorphisms of XPA gene have been studied in several cancers such as rs10817938, rs2808668. However, the role of XPA polymorphisms in patients with oral squamous cell carcinoma (OSCC) remains unclear. Thus, we analyzed the association of XPA polymorphisms with OSCC risk, clinicopathological characteristics and prognosis in the present study. TaqMan genotyping was used to evaluate the frequency of rs10817938, rs2808668 polymorphisms in OSCC patients. The prognostic significance of these polymorphisms was evaluated using Kaplan-Meier curves, Log-Rank analyses, and the Cox proportional hazard model. Luciferase reporter assay, RT-PCR and western blot were used to determine whether rs10817938 could influence transcription activity and XPA expression. The results showed that individuals carrying TC and CC genotypes had significantly greater risk of developing OSCC (OR = 1.42, 95% CI 1.04–1.93; OR = 2.75, 95% CI 1.32–5.71, respectively) when compared with wild-type TT genotype at rs10817938. OSCC patients with C allele at rs10817938 were more susceptible to lymph metastases, poor pathological differentiation and late TNM stage (OR = 1.67, 95% CI 1.17–2.37; OR = 1.64, 95% CI 1.18–2.28; OR = 1.54, 95% CI 1.11–2.14; respectively). A significant gene-environment interaction between smoking and CC genotype at rs10817938 was observed (COR = 3.60, 95% CI 1.20–10.9) and data also showed that OSCC patients with CC genotype and C allele had worse survival (p<0.001 for both). The T to C substitution at rs10817938 significantly decreased transcription activity of XPA gene, XPA mRNA and protein were also decreased in individuals with C allele at rs10817938. In addition, no significant association of rs2808668 polymorphism with OSCC risk, prognosis could be observed. In conclusion, the present study showed that XPA rs10817938 polymorphism is a functional SNP in vitro and in vivo and a biomarker for poor prognosis in OSCC patients. PMID:27622501

  2. INFeRS: Interactive Numeric Files Retrieval System. Final Report.

    ERIC Educational Resources Information Center

    Chiang, Katherine; And Others

    In 1988 Mann Library at Cornell University proposed to develop a computer system that would support interactive access to significant electronic files in agriculture and the life sciences. This system was titled the Interactive Numeric Files Retrieval System (INFeRS). This report describes how project goals were met and it presents the project's…

  3. Work in Progress: The Seven Rs of Team Building

    ERIC Educational Resources Information Center

    Brunelli, Jean; Schneider, Elaine Fogel

    2004-01-01

    This article argues that supportive teams--including professionals, paraprofessionals, and parents--can teach staff members how to identify and implement best practices in early intervention settings. The authors describe "the seven Rs of team building" distilled from their many years of team building and maintenance: 1) Reading cues; 2) Regular…

  4. SRPK1 and Akt Protein Kinases Phosphorylate the RS Domain of Lamin B Receptor with Distinct Specificity: A Combined Biochemical and In Silico Approach

    PubMed Central

    Nikolakaki, Eleni; Vlassi, Metaxia; Giannakouros, Thomas

    2016-01-01

    Activated Akt has been previously implicated in acting on RS domain-containing proteins. However, it has been questioned whether its action is direct or it is mediated by co-existing SR kinase activity. To address this issue we studied in detail the phosphorylation of Lamin B Receptor (LBR) by Akt. Using synthetic peptides and a set of recombinant proteins expressing mutants of the LBR RS domain we now demonstrate that while all serines of the RS domain represent more or less equal phosphoacceptor sites for SRPK1, Ser80 and Ser82 are mainly targeted by Akt. 3D-modeling combined with molecular dynamics (MD) simulations show that amongst short, overlapping LBR RS-containing peptides complying with the minimum Akt recognition consensus sequence, only those bearing phosphosites either at Ser80 or Ser82 are able to fit into the active site of Akt, at least as effectively as its known substrate, GSK3-β. Combined our results provide evidence that Akt kinases directly phosphorylate an RS domain-containing protein and that both the residues N-terminal the phosphosite and at position +1 are essential for Akt specificity, with the latter substrate position being compatible with the arginine residue of RS-repeats. PMID:27105349

  5. The rs3736228 polymorphism in the LRP5 gene is associated with calcaneal ultrasound parameter but not with body composition in a cohort of young Caucasian adults.

    PubMed

    Correa-Rodríguez, María; Schmidt-RioValle, Jacqueline; Rueda-Medina, Blanca

    2016-12-27

    The aim of the present study was to investigate the possible influence of low-density lipoprotein receptor-related protein 5 (LRP5) and sclerostin (SOST) genes as genetic factors contributing to calcaneal quantitative ultrasound (QUS) and body composition variables in a population of young Caucasian adults. The study population comprised a total of 575 individuals (mean age 20.41years; SD 2.36) whose bone mass was assessed through QUS to determine broadband ultrasound attenuation (BUA, dB/MHz). Body composition measurements were performed using a body composition analyser. Seven single-nucleotide polymorphisms (SNPs) of LRP5 (rs2306862, rs599083, rs556442 and rs3736228) and SOST (rs4792909, rs851054 and rs2023794) were selected as genetic markers and genotyped using TaqMan OpenArray(®) technology. Linear regression analysis was used to test the possible association of the tested SNPs with QUS and body composition parameters. Linear regression analysis revealed that the rs3736228 SNP of LPR5 was significantly associated with BUA after adjustment for age, sex, weight, height, physical activity and calcium intake (P = 0.028, β (95% CI) = 0.089 (0.099-1.691). For the remaining SNPs, no significant association with the QUS measurement was observed. Regarding body composition, no significant association was found between LRP5 and SOST polymorphisms and body mass index, total fat mass and total lean mass after adjustment for age and sex as covariates. We concluded that the rs3736228 LRP5 genetic polymorphism influences calcaneal QUS parameter in a population of young Caucasian adults. This finding suggests that LRP5 might be an important genetic marker contributing to bone mass accrual early in life.

  6. TLR1 polymorphism rs4833095 as a risk factor for IgA nephropathy in a Chinese Han population: A case-control study

    PubMed Central

    Wei, Jiali; Yao, Ganglian; Wang, Li; Wang, Meng; Liu, Xinghan; Dai, Cong; Jin, Tianbo; Dai, Zhijun; Fu, Rongguo

    2016-01-01

    Toll-like receptors (TLRs) are a family of transmembrane receptors, and play a vital role in recognizing invading pathogens and activating innate immunity. Previous studies indicated that TLR1 single nucleotide polymorphisms (SNPs) might be associated with the risk of IgA nephropathy (IgAN). This study aims to investigate the relationship between TLR1 SNPs (rs4833095 and rs5743557) and IgAN in a Chinese Han population. This case-control study included 351 patients with IgAN and 310 healthy controls. Two SNPs (rs4833095 and rs5743557) of TLR1 were genotyped by Sequenom MassARRAY. Odds ratios (OR) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. We found that both allele and genotype frequencies of rs5743557 were not associated with IgAN risk. Rs4833095 increased IgAN risk compared with controls in the allele, dominant and log-additive models (P = 0.04, 0.04 and 0.03, respectively). Further haplotype analysis revealed that the Trs4833095Trs5743557 haplotype may be a risk factor for IgAN (OR = 1.28; 95% CI = 1.01–1.63; P = 0.046). Furthermore, rs4833095 was associated with Lee's grades (OR = 1.75; 95% CI = 1.03–2.96; P = 0.04). However, there was no significant association between the genotype distributions of rs5743557 and clinical parameters of IgAN such as gender, 24 hour urine protein, blood pressure, and Lee's grades. Taken together, these findings suggest that the TLR1 rs4833095 polymorphism may play a role in the development and progression of IgAN. PMID:27806314

  7. Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.

    PubMed

    Flores, Yvonne N; Velázquez-Cruz, Rafael; Ramírez, Paula; Bañuelos, Manuel; Zhang, Zuo-Feng; Yee, Hal F; Chang, Shen-Chih; Canizales-Quinteros, Samuel; Quiterio, Manuel; Cabrera-Alvarez, Guillermo; Patiño, Nelly; Salmerón, Jorge

    2016-12-01

    There is scarce information about the link between specific single-nucleotide polymorphisms (SNPs) and risk of liver disease among Latinos, despite the disproportionate burden of disease among this population. Our aim was to investigate nine SNPs in or near the following genes: PNPLA3, LYPLAL1, PPP1R3B, GCKR, NCAN, IRS1, PPARG, and ADIPOR2 and examine their association with persistently elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels in Mexican adults. Data and samples were collected from 741 participants in the Mexican Health Worker Cohort Study, in Cuernavaca, Mexico. We identified 207 cases who had persistently elevated levels of ALT or AST (≥40 U/L) and 534 controls with at least two consecutive normal ALT or AST results in a 6 month period, during 2004-2006 and 2011-2013. TaqMan assays were used to genotype the SNPs. The risk allele of PNPLA3 rs738409 was found to be associated with persistently elevated levels of ALT or AST, adjusting for age, sex, BMI, type 2 diabetes, and ancestry: (OR 2.28, 95 % CI 1.13, 4.58). A significant association was found between the LYPLAL1, PPP1R3B, and GCKR risk alleles and elevated ALT or AST levels among overweight/obese adults. These results suggest that among Mexicans, the PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) polymorphisms may be associated with a greater risk of chronic liver disease among overweight adults. This study is the first to examine these nine SNPs in a sample of adults in Mexico.

  8. Optical studies of X-ray peculiar chromosphereically active stars

    NASA Astrophysics Data System (ADS)

    Pandey, J. C.

    2006-02-01

    of high level of chromospheric activity. The chromospheric line emission for both stars seems to correlate with the photometric light curve, i.e. maximum at the light curve minimum, or minimum at the light curve maximum. The value of 5.3 for the ratio of the excess emission in Halpha to Hbeta, EHalpha/EHbeta for the star FR Cnc, suggests that the chromospheric emission May arise from an extended off-limb region. We have searched for the presence of color excesses in the near-IR JHK bands of these stars using 2MASS data, but none of them appear to have any significant color excess. The kinematics of the stars FR Cnc, HD 95559, HD 160934 and LO Peg suggest that these are younger than 0.6 Gyrs. The archival X-ray observations of HD 81032, HD 95559, HD 160934 and LO Peg carried out by with the ROSAT observatory were also analyzed. We did not find any significant variability in the X-ray light curve of the stars HD 95559. However, it appears from the X-ray light curve of HD 81032 that a moderate flare occurred during the RASS observations, with a peak of about 0.6 ct s^{-1} at approximately JD=244806.95 and half decay time of 2.6 x 10^4 s. A similar flare was also observed in HD 160934 with a peak about 0.2 ct s^{-1} (above its mean level) at JD = 2448123.12. A significant variability was found in the X-ray light curve of LO Peg. Rotational modulation appears to be present in the X-ray light curve of LO Peg. The best fit models to their X-ray spectra imply the presence of two coronal plasma components of differing temperatures and with sub-solar metal abundances. The inferred emission measures and temperatures of HD 95559 and LO Peg are similar to those found for other active dwarf stars. The observed X-ray spectrum and the inferred coronal plasma parameters for HD 81032 are typical of those seen in active stars such as RS CVn binaries. All of the optical and X-ray properties found for FR Cnc, HD 95559, HD 160934 and LO Peg are most consistent to the BY Dra type. However

  9. Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS domain on either the large or small Drosophila subunit is dispensable in vivo

    PubMed Central

    Rudner, David Z.; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The pre-mRNA splicing factor U2AF (U2 snRNP auxiliary factor) has an essential role in 3′ splice site selection. U2AF binds the intron pyrimidine tract between the branchpoint and the 3′ splice site and recruits U2 snRNP to the branch site at an early step in spliceosome assembly. Human U2AF is a heterodimer composed of large (hU2AF65) and small (hU2AF35) subunits. Both subunits contain a domain enriched in arginine–serine dipeptide repeats termed an RS domain. The two U2AF RS domains have been assigned essential and independent roles in spliceosome assembly in vitro—the hU2AF65 RS domain is required to target U2 snRNP to the branch site and the hU2AF35 RS domain is necessary for protein–protein interactions with constitutive and alternative splicing factors. We have investigated the functional requirements for the RS domains on the Drosophila U2AF homolog in vivo. In sharp contrast to its essential role in U2 snRNP recruitment in vitro, the RS domain on the Drosophila large subunit homolog (dU2AF50) was completely dispensable in vivo. Prompted by this unexpected result, we analyzed the RS domain on the Drosophila small subunit homolog (dU2AF38). Despite its requirement for enhancer-dependent splicing activity in vitro, the dU2AF38 RS domain was also inessential in vivo. Finally, we have tested whether the Drosophila U2AF heterodimer requires any RS domain. Flies mutant for both the small and large subunits could not be rescued by dU2AF50ΔRS and dU2AF38ΔRS transgenes. Therefore, in contrast to the separate roles assigned to the U2AF RS domains in vitro, our genetic data suggest that they may have redundant functions in vivo. PMID:9531538

  10. Association of rs10757274 and rs2383206 Polymorphisms on 9p21 locus with Coronary Artery Disease in Turkish Population

    PubMed Central

    Okyay, Kaan; Yılmaz, Akın; Şahinarslan, Asife; Yar Sağlam, Atiye Seda; Eyiol, Azmi; Bolayır, Hasan Ata; Sezenöz, Burak; Menevşe, Sevda; Çengel, Atiye

    2016-01-01

    Background and Objectives Genetic predisposition is an important risk factor for coronary artery disease (CAD). In this study, we aimed to evaluate the impact of rs10757274 and rs2383206 polymorphisms in chromosome 9p21 on presence and severity of CAD in a Turkish population. Subjects and Methods A total of 646 patients who underwent coronary angiography were included in this study. Coronary vessel score and Gensini score were calculated to assess the angiographic severity of CAD. Alleles of AA, AG, and GG were determined for rs10757274 (polymorphism-1) and rs2383206 (polymorphism-2) polymorphisms located in chromosome 9p21 from the blood samples. Results There was a significant difference between the alleles in polymorphism-1 in the presence of coronary artery disease (38.9% in AA, 48.0% in GG and 56.4% in AG, p=0.017). However, there was no difference between the alleles in polymorphism-2. According to vessel scores, there was a significant difference between the alleles in polymorphism-1 (AA 0.71±1.04, GG 0.88±1.07, AG 1.06±1.12, p=0.018). In polymorphism-2, vessel scores did not show a difference between the alleles. In polymorphism-1, there was a significant difference in Gensini score (p=0.041). Gensini scores did not differ between the alleles in polymorphism-2 (p>0.05 for all). In multivariate analyses, none of the alleles was an independent factor for presence of CAD. Conclusion The presence of rs10757274 polymorphism including AG allele in chromosome 9p21 was related to CAD. However, this relationship was not independent of other cardiovascular risk factors. PMID:27721851

  11. Matrix Metalloproteinase-9 Polymorphism 1562 C > T (rs3918242) Associated with Protection against Placental Malaria

    PubMed Central

    Apoorv, Thittayil Suresh; Babu, Phanithi Prakash; Meese, Stefanie; Gai, Prabhanjan P.; Bedu-Addo, George; Mockenhaupt, Frank P.

    2015-01-01

    Phagocytosis of malaria pigment (hemozoin) induces increased activity of matrix metalloproteinase (MMP)-9, an endopeptidase involved in cytokine regulation. In this study, we examined whether a common functional MMP-9 promoter polymorphism (rs3918242) affects Plasmodium falciparum infection in pregnancy. Eighteen percent of Ghanaian primiparae carried the minor T allele. It was associated with reduced odds of placental hemozoin and of placental as well as peripheral blood parasitemia. The results indicate that a common MMP-9 polymorphism protects against placental malaria indicating that this endopeptidase is involved in susceptibility to P. falciparum. PMID:26013370

  12. Association of the IGF-1 rs35767 and rs972936 polymorphisms with the risk of osteoporosis in a Chinese postmenopausal female population.

    PubMed

    Wei, Y K; Ma, H L; Guo, Y Z; Yang, B H; Pang, W X

    2015-11-13

    The aim of our study was to conduct a case-control study in a Chinese postmenopausal population to evaluate the roles of the IGF-1 rs35767 and rs972936 polymorphisms on bone mineral density (BMD) levels and osteoporosis risk. A total of 272 consecutive postmenopausal women with a primary diagnosis of osteoporosis and 272 controls were enrolled in the study between 2012 and 2014. The polymerase chain reaction-restriction fragment length polymorphism method was used to genotype the rs35767 and rs972936 IGF-1 polymorphisms. By comparing the demographic characteristics between patients and controls, patients with osteoporosis were found to be more likely to have a habit of alcohol drinking (P = 0.023). Furthermore, the BMD levels of the L1-L4 vertebrae, femoral necks, total hips, and trochanters in patients with osteoporosis were significantly lower than those in controls. By conditional regression analysis, we found that the IGF-1 rs2288377 and rs972936 gene polymorphisms were not associated with the risk of osteoporosis (P < 0.05). However, the CT+TT genotype of rs35767 and the AG+GG genotype of rs972936 were significantly associated with lower BMD levels in the femoral neck. Overall, our study suggests that IGF-1 rs2288377 and rs972936 gene polymorphisms do not influence the risk osteoporosis.

  13. Evolved Expandable Launch Vehicle System: RS-68 Main Engine Development

    NASA Astrophysics Data System (ADS)

    Portanova, P. L.; Conley, D. S., , Capt; Lee, N. Y.; Wood, B. K.

    2002-01-01

    Delta IV is one of two competing Evolved Expendable Launch Vehicle (EELV) systems being developed in an industry/United States Government partnership to meet the need for the new era of space transportation for the early decades of the 21st Century. The Boeing Company, Rocketdyne, and United States Air Force have developed a 650 Klbf (2.9 NM) class liquid hydrogen/liquid oxygen main engine for the Delta IV family of EELV. The purpose of this paper is to present the innovative approach to the design, development, testing, and certification of the RS-68 engine over the last several years. With the initial production process underway, RS-68 is implementing additional innovative concepts to produce an affordable main engine, and provide assured access to space. 1) The Aerospace Corporation3) The Aerospace Corporation 2) Captain, United States Air Force4) The Boeing Company/Rocketdyne

  14. Journal editorial policies, animal welfare, and the 3Rs.

    PubMed

    Osborne, Nicola J; Payne, Daisy; Newman, Michael L

    2009-12-01

    This study evaluates the editorial policies of a randomized sample of English language peer-reviewed journals that publish original research involving the use of animals. The aim is to identify whether journals have editorial policies relating to the use of animals in the research that they are prepared to publish and whether any policies are likely to promote animal welfare and dissemination of information on the 3Rs (reduction, refinement, replacement) within the scientific community. The results demonstrate that a significant proportion of journals publishing original research involving animals do not have any editorial policy relating to the use of animals. Of those journals that do have policies the majority simply request that the research be carried out in accordance with standard regulatory requirements. This paper aims to provide editors and publishers with the information they need to review their own editorial policies to ensure they are fulfilling their potential to promote animal welfare and dissemination of the 3Rs.

  15. Radiation Dry Bias of the Vaisala RS92 Humidity Sensor

    NASA Technical Reports Server (NTRS)

    Vomel, H.; Selkirk, H.; Miloshevich, L.; Valverde-Canossa, J.; Valdes, J.; Kyro, E.; Kivi, R.; Stolz, W.; Peng, G.; Diaz, J. A.

    2007-01-01

    The comparison of simultaneous humidity measurements by the Vaisala RS92 radiosonde and by the Cryogenic Frostpoint Hygrometer (CFH) launched at Alajuela, Cosla Rica, during July 2005 reveals a large solar radiation dry bias of the Vaisala RS92 humidity sensor and a minor temperature-dependent calibration error. For soundings launched at solar zenith angles between 10" and 30 , the average dry bias is on the order of 9% at the surface and increases to 50% at 15 km. A simple pressure- and temperature-dependent correction based on the comparison with the CFH can reduce this error to less than 7% at all altitudes up to 15.2 km, which is 700 m below the tropical tropopause. The correction does not depend on relative humidity, but is able to reproduce the relative humidity distribution observed by the CFH.

  16. Higher Curvature Effects in the ADD and RS Models

    SciTech Connect

    Rizzo, Thomas G.; /SLAC

    2006-07-05

    Over the last few years several extra-dimensional models have been introduced in attempt to deal with the hierarchy problem. These models can lead to rather unique and spectacular signatures at Terascale colliders such as the LHC and ILC. The ADD and RS models, though quite distinct, have many common feature including a constant curvature bulk, localized Standard Model(SM) fields and the assumption of the validity of the EH action as a description of gravitational interactions.

  17. Association of vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the nephrolithiasis susceptibility.

    PubMed

    Zhou, Tian-Biao; Jiang, Zong-Pei; Li, Ai-Hua; Ju, Lang

    2015-04-01

    Association of vitamin D receptor (VDR) gene polymorphism with the risk of nephrolithiasis from the published reports is still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk of nephrolithiasis using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with nephrolithiasis susceptibility. In this meta-analysis, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis susceptibility for overall populations and in Caucasians. However, the Fok1 f allele and ff genotype were associated with the risk of nephrolithiasis in Asians, but the FF genotype not. Furthermore, TaqI TT genotype was associated with the risk of nephrolithiasis in Asians, but the t allele and tt genotype not. However, ApaI gene polymorphism was not associated with nephrolithiasis susceptibility in Asians. In conclusion, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis risk in overall populations and in Caucasians. But, the Fok1 f allele and ff genotype, TaqI TT genotype, ApaI gene polymorphism were associated with the risk of nephrolithiasis in Asians. However, more studies should be conducted to confirm it.

  18. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons

    PubMed Central

    Yang, Bo; Rajput, Padmesh S.; Kumar, Ujendra; Sastry, Bhagavatula R.

    2015-01-01

    The equilibrium potential for GABA-A receptor mediated currents (EGABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2) but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary. PMID:26389591

  19. Alkaline protease from Thermoactinomyces sp. RS1 mitigates industrial pollution.

    PubMed

    Verma, Amit; Ansari, Mohammad W; Anwar, Mohmmad S; Agrawal, Ruchi; Agrawal, Sanjeev

    2014-05-01

    Proteases have found a wide application in the several industrial processes, such as laundry detergents, protein recovery or solubilization, prion degradation, meat tenderizations, and in bating of hides and skins in leather industries. But the main hurdle in industrial application of proteases is their economical production on a large scale. The present investigation aimed to exploit the locally available inexpensive agricultural and household wastes for alkaline protease production using Thermoactinomyces sp. RS1 via solid-state fermentation (SSF) technique. The alkaline enzyme is potentially useful as an additive in commercial detergents to mitigate pollution load due to extensive use of caustic soda-based detergents. Thermoactinomyces sp. RS1 showed good protease production under SSF conditions of 55 °C, pH 9, and 50 % moisture content with potato peels as solid substrate. The presented findings revealed that crude alkaline protease produced by Thermoactinomyces sp. RS1 via SSF is of potential application in silver recovery from used X-ray films.

  20. IRF4 rs12203592 functional variant and melanoma survival.

    PubMed

    Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

    2017-04-15

    Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour.

  1. PSCA rs2294008 Polymorphism with Increased Risk of Cancer

    PubMed Central

    Geng, Peiliang; Li, Jianjun; Wang, Ning; Ou, Juanjuan; Xie, Ganfeng; Liu, Chen; Zhao, Xiaoxin; Xiang, Lisha; Liao, Yunmei; Liang, Houjie

    2015-01-01

    Background Published data on the association between PSCA rs2294008 polymorphism and cancer risk have implicated inconclusive results. To determine the relationship and to precisely assess the effect size estimate of the association, we performed a meta-analysis. Methods We searched published literature in Embase and PubMed databases using the search terms “PSCA”, “prostate stem cell antigen”, “variants”, “polymorphism”, “polymorphisms”, and “cancer”. A total of 21 eligible articles were retrieved, with 27, 197 cancer cases and 48, 237 controls. Results On the whole, we found the association between PSCA rs2294008 polymorphism and cancer risk was statistically significant: TT vs CC: OR = 1.18, 95% CI, 1.10 to 1.27; TT + CT vs CC: OR = 1.08, 95% CI, 1.05 to 1.10; TT vs CT + CC: OR = 1.14, 95% CI, 1.07 to 1.21; T vs C: OR = 1.10, 95% CI, 1.06 to 1.14; CT vs CC: OR = 1.10, 95% CI, 1.06 to 1.13. Stratified analyses in cancer type and ethnicity showed similar results. Conclusions Based on the statistical evidence, we can draw a conclusion that the rs2294008 polymorphism of PSCA gene is likely to play a role in cancer carcinogenesis, especially in gastric cancer and bladder cancer. PMID:26308216

  2. The antifungal plant defensin RsAFP2 from radish induces apoptosis in a metacaspase independent way in Candida albicans.

    PubMed

    Aerts, An M; Carmona-Gutierrez, Didac; Lefevre, Sophie; Govaert, Gilmer; François, Isabelle E J A; Madeo, Frank; Santos, Renata; Cammue, Bruno P A; Thevissen, Karin

    2009-08-06

    We show that the antifungal plant defensin Raphanus sativus antifungal protein 2 (RsAFP2) from radish induces apoptosis and concomitantly triggers activation of caspases or caspase-like proteases in the human pathogen Candida albicans. Furthermore, we demonstrate that deletion of C. albicans metacaspase 1, encoding the only reported (putative) caspase in C. albicans, significantly affects caspase activation by the apoptotic stimulus acetic acid, but not by RsAFP2. To our knowledge, this is the first report on the induction of apoptosis with concomitant caspase activation by a defensin in this pathogen. Moreover, our data point to the existence of at least two different types of caspases or caspase-like proteases in C. albicans.

  3. Choline Dehydrogenase Polymorphism rs12676 Is a Functional Variation and Is Associated with Changes in Human Sperm Cell Function

    PubMed Central

    Johnson, Amy R.; Lao, Sai; Wang, Tongwen; Galanko, Joseph A.; Zeisel, Steven H.

    2012-01-01

    Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh−/− males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm. PMID:22558321

  4. The RAD51-stimulatory compound RS-1 can exploit the RAD51 overexpression that exists in cancer cells and tumors

    PubMed Central

    Mason, Jennifer M; Logan, Hillary L.; Budke, Brian; Wu, Megan; Pawlowski, Michal; Weichselbaum, Ralph R.; Kozikowski, Alan P.; Bishop, Douglas K.; Connell, Philip P.

    2014-01-01

    RAD51 is the central protein that catalyzes DNA repair via homologous recombination (HR), a process that ensures genomic stability. RAD51 protein is commonly expressed at high levels in cancer cells relative to their non-cancerous precursors. High levels of RAD51 expression can lead to the formation of genotoxic RAD51 protein complexes on undamaged chromatin. We developed a therapeutic approach that exploits this potentially toxic feature of malignancy, using compounds that stimulate the DNA binding activity of RAD51 to promote cancer cell death. A panel of immortalized cell lines was challenged with the RAD51-stimulatory compound RS-1. Resistance to RS-1 tended to occur in cells with higher levels of RAD54L and RAD54B, which are Swi2/Snf2-related translocases known to dissociate RAD51 filaments from double-stranded DNA. In PC3 prostate cancer cells, RS-1 induced lethality was accompanied by the formation of microscopically visible RAD51 nuclear protein foci occurring in the absence of any DNA-damaging treatment. Treatment with RS-1 promoted significant anti-tumor responses in a mouse model, providing proof of principle for this novel therapeutic strategy. PMID:24753542

  5. Associations of the calcium-sensing receptor gene CASR rs7652589 SNP with nephrolithiasis and secondary hyperparathyroidism in haemodialysis patients

    PubMed Central

    Grzegorzewska, Alicja E.; Paciorkowski, Mateusz; Mostowska, Adrianna; Frycz, Bartosz; Warchoł, Wojciech; Stolarek, Ireneusz; Figlerowicz, Marek; Jagodziński, Paweł P.

    2016-01-01

    Nephrolithiasis, secondary hyperparathyroidism (sHPT), and cardiovascular complications are associated with disturbances in Ca handling and contribute to morbidity/mortality during haemodialysis (HD). Calcimimetics, activators of the calcium-sensing receptor (CaSR), provide an effective means of reducing parathyroid hormone (PTH) secretion in sHPT. Polymorphism in CaSR gene (CASR) influences Ca-related parameters, however it was not shown in HD patients for CASR rs7652589. The minor allele at this polymorphism modifies the binding sites of transcription factors and CaSR expression. We hypothesized that CASR rs7652589 variants may also influence CaSR in end stage renal disease (ESRD). We aimed to determine the associations of rs7652589 with nephrolithiasis-related ESRD, Ca, P, ALP, PTH, response to treatment with cinacalcet, prevalence of coronary artery disease, and all-cause/cardiovascular mortality in HD patients (n = 1162). Healthy individuals (n = 918) were controls. This study shows that the A allele of rs7652589 is a risk allele for nephrolithiasis-related ESRD. The AA genotype is associated with more severe sHPT (higher Ca and PTH concentrations). The A allele is associated with reduced CaSR transcript level in peripheral blood mononuclear cells. According to computational analysis, potential binding sites for GLI3, AHR and TP53 are removed by the A allele, whereas binding sites for SOX18 and TP63 are created. PMID:27739473

  6. Association Between Dentin Matrix Protein 1 (rs10019009) Polymorphism and Ankylosing Spondylitis in a Chinese Han Population from Shandong Province

    PubMed Central

    Liu, Jian-Min; Cui, Ya-Zhou; Zhang, Geng-Lin; Zhou, Xiao-Yan; Pang, Jing-Xiang; Wang, Xue-Zheng; Han, Jin-Xiang

    2016-01-01

    Background: Ankylosing spondylitis (AS) is the most common rheumatic condition that is slowly progressive and predominantly affects adolescents. Pathological bone formation associated with AS is an important cause of disability. The aim of the study was to investigate the possible involvement of the genes related to endochondral ossification and ectopia ossification in genetic susceptibility to AS in a Chinese Han population. Methods: Sixty-eight single nucleotide polymorphisms (SNPs) from 13 genes were genotyped in discovery cohorts including 300 AS patients and 180 healthy controls. The rs10019009 in dentin matrix protein 1 (DMP1) gene shown as association with AS after multiple testing corrections in discovery cohorts was replicated in a validation independent cohort of 620 AS patients and 683 healthy controls. The rs10019009 was assessed with bioinformatics including phylogenetic context, F-SNP and FastSNP functional predictions, secondary structure prediction, and molecular modeling. We performed a functional analysis of rs10019009 via reverse transcription-polymerase chain reaction, alkaline phosphatase (ALP) activity in human osteosarcoma U2OS cells. Results: Interestingly, the SNP rs10019009 was associated with AS in both the discovery cohort (P = 0.0012) and validation cohort (P = 0.0349), as well as overall (P = 0.0004) in genetic case–control association analysis. After a multivariate logistic regression analysis, the effect of this genetic variant was observed to be independent of linkage disequilibrium. Via bioinformatics analysis, it was found that the amino acid change of the rs10019009 led to changes of SNP function, secondary structure, tertiary conformation, and splice mode. Finally, functional analysis of rs10019009 in U2OS cells demonstrated that the risk T allele of the rs10019009 increased enzymatic activity of ALP, compared to that of the nonrisk allele (P = 0.0080). Conclusions: These results suggested that the DMP1 gene seems to be

  7. Time-series Doppler imaging of the red giant HD 208472. Active longitudes and differential rotation

    NASA Astrophysics Data System (ADS)

    Özdarcan, O.; Carroll, T. A.; Künstler, A.; Strassmeier, K. G.; Evren, S.; Weber, M.; Granzer, T.

    2016-10-01

    Context. HD 208472 is among the most active RS CVn binaries with cool starspots. Decade-long photometry has shown that the spots seem to change their longitudinal appearance with a period of about six years, coherent with brightness variations. Aims: Our aim is to spatially resolve the stellar surface of HD 208472 and relate the photometric results to the true longitudinal and latitudinal spot appearance. Furthermore, we investigate the surface differential rotation pattern of the star. Methods: We employed three years of high-resolution spectroscopic data with a high signal-to-noise ratio (S/N) from the STELLA robotic observatory and determined new and more precise stellar physical parameters. Precalculated synthetic spectra were fit to each of these spectra, and we provide new spot-corrected orbital elements. A sample of 34 absorption lines per spectrum was used to calculate mean line profiles with a S/N of several hundred. A total of 13 temperature Doppler images were reconstructed from these line profiles with the inversion code iMap. Differential rotation was investigated by cross-correlating successive Doppler images in each observing season. Results: Spots on HD 208472 are distributed preferably at high latitudes and less frequently around mid-to-low latitudes. No polar-cap like structure is seen at any epoch. We observed a flip-flop event between 2009 and 2010, manifested as a flip of the spot activity from phase 0.0 to phase 0.5, while the overall brightness of the star continued to increase and reached an all-time maximum in 2014. Cross-correlation of successive Doppler images suggests a solar-like differential rotation that is ≈15 times weaker than that of the Sun. Based on data obtained with the STELLA robotic telescope in Tenerife, an AIP facility jointly operated by AIP and IAC, and the Potsdam Automatic Photoelectric Telescopes (APT) in Arizona, jointly operated by AIP and Fairborn Observatory.Radial velocity measurements are only available at the

  8. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study

    PubMed Central

    2016-01-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout. PMID:27550484

  9. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study.

    PubMed

    Lee, Sung Won; Lee, Shin Seok; Oh, Dong Ho; Park, Dong Jin; Kim, Hyun Sook; Choi, Jung Ran; Chae, Soo Cheon; Yun, Ki Jung; Chung, Won Tae; Choe, Jung Yoon; Kim, Seong Kyu

    2016-10-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

  10. Physico-chemical, functional and structural properties of RS3/RS4 from kidney bean (Phaseolus vulgaris) cultivars.

    PubMed

    Gani, Adil; Jan, Amreen; Shah, Asima; Masoodi, F A; Ahmad, Mudasir; Ashwar, Bilal Ahmad; Akhter, Rehana; Wani, Idrees Ahmed

    2016-06-01

    Starch isolated from four kidney bean cultivars (Yellow bean, Red bean, Black bean and White bean) were physically and chemically modified in order to prepare resistant starch (RS3/RS4). Following the Heat-moisture treatment (HMT) and Citric acid modification (CT) of the native starch, the amylose content got decreased whereas bulk and tapped density (g/ml) increased. Both HMT and CT reduced the swelling power and the solubility of native starch. Pasting temperature increased and peak, breakdown, final, and set-back viscosity decreased after both the modifications. Fourier Transform Infrared Spectroscopy (FTIR) analysis displayed peaks at 1020cm(-1) in HMT and 1724cm(-1) in CT starches. Differential Scanning Calorimetry (DSC) analysis revealed that samples were more stable after modification. X-ray diffraction (XRD) analysis revealed reordering of chain segments to more crystalline structure. These results suggested modifications resulted in starch with improved properties and could be a possible method for the RS preparation with better thermal stability.

  11. TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population.

    PubMed

    Xu, Pengcheng; Guo, Wen; Jin, Tianbo; Wang, Jihong; Fan, Dongsheng; Hao, Zengtao; Jing, Shangfei; Han, ChaoQian; Du, Jieli; Jiang, Dong; Wen, Shuzheng; Wang, Jianzhong

    2017-01-03

    This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele "A" in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease.

  12. TIMP-2 SNPs rs7342880 and rs4789936 are linked to risk of knee osteoarthritis in the Chinese Han Population

    PubMed Central

    Jin, Tianbo; Wang, Jihong; Fan, Dongsheng; Hao, Zengtao; Jing, Shangfei; Han, ChaoQian; Du, Jieli; Jiang, Dong; Wen, Shuzheng; Wang, Jianzhong

    2017-01-01

    This study aimed to investigate whether functional polymorphisms in the tissue inhibitors of metalloproteinase-2 (TIMP-2) gene are associated with susceptibility to knee osteoarthritis (OA) in the Chinese Han population. Six TIMP-2 single nucleotide polymorphisms (SNPs) were assayed using MassARRAY in 300 patients clinically and radiographically diagnosed with knee OA and in 428 controls. Allelic and genotypic frequencies were compared between groups. Logistic regression adjusting for age and gender was used to estimate risk associations between specific genotypes and knee OA by computing odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that allele “A” in rs7342880 was significantly associated with increased risk of knee OA (OR = 1.44, 95%CI = 1.09-1.91, p = 0.035). In addition, in the over-dominant model, rs4789936 correlated with reduced risk of knee OA, adjusting for age and gender (OR = 0.69, 95%CI = 0.49-0.98, p = 0.036). Finally, rs7342880 correlated with increased risk of knee OA in females. This study provides evidence that TIMP-2 is a knee OA susceptibility gene in the Chinese population and a potential diagnostic and preventive marker for the disease. PMID:27901480

  13. Co-ordinated Ginga, IUE and VLA observations of flaring activity in sigma-squared CrB

    NASA Technical Reports Server (NTRS)

    Stern, R. A.; Haisch, B. M.; Uchida, Y.; Walter, F.; Veale, A.

    1990-01-01

    The RS CVn system sigma-squared CrB was observed by the Ginga X-ray satellite for a period of 2.5 days, or approximately 2 binary orbits. Sigma-squared CrB exhibited almost continuous X-ray variability on time scales ranging from minutes to days, including several 'flare-like' episodes with increased coronal temperature. The average count rate was 4.2 +/- 1.2 cts/s (1.7-11.0 keV) corresponding to L(x) of about 10 to the 29.6th erg/s (2-10 keV). Coordinated observations with IUE and the VLA indicate microwave and ultraviolet flaring associated with one X-ray flare.

  14. Effects of Two Common Polymorphisms rs2910164 in miR-146a and rs11614913 in miR-196a2 on Gastric Cancer Susceptibility

    PubMed Central

    Ni, Qing; Yin, Junfeng; Wang, Xiangjun; Liu, Xinnong

    2015-01-01

    Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect. PMID:25983750

  15. Identification of the Functional Variant(s) that Explain the Low-Density Lipoprotein Receptor (LDLR) GWAS SNP rs6511720 Association with Lower LDL-C and Risk of CHD

    PubMed Central

    Palmen, Jutta; Kalea, Anastasia Z.

    2016-01-01

    Background The Low-Density Lipoprotein Receptor (LDLR) SNP rs6511720 (G>T), located in intron-1 of the gene, has been identified in genome-wide association studies (GWAS) as being associated with lower plasma levels of LDL-C and a lower risk of coronary heart disease (CHD). Whether or not rs6511720 is itself functional or a marker for a functional variant elsewhere in the gene is not known. Methods The association of LDLR SNP rs6511720 with incidence of CHD and levels of LDL-C was determined by reference to CARDIoGRAM, C4D and Global lipids genetics consortium (GLGC) data. SNP annotation databases were used to identify possible SNP function and prioritization. Luciferase reporter assays in the liver cell line Huh7 were used to measure the effect of variant genotype on gene expression. Electrophoretic Mobility Shift Assays (EMSAs) were used to identify the Transcription Factors (TFs) involved in gene expression regulation. Results The phenotype-genotype analysis showed that the rs6511720 minor allele is associated with lower level of LDL-C [beta = -0.2209, p = 3.85 x10-262], and lower risk of CHD [log (OR) = 0.1155, p = 1.04 x10-7]. Rs6511720 is in complete linkage. Rs6511720 is in complete linkage disequilibrium (LD) with three intron-1 SNPs (rs141787760, rs60173709, rs57217136). Luciferase reporter assays in Huh7 cells showed that the rare alleles of both rs6511720 and rs57217136 caused a significant increase in LDLR expression compared to the common alleles (+29% and +24%, respectively). Multiplex Competitor-EMSAs (MC-EMSA) identified that the transcription factor serum response element (SRE) binds to rs6511720, while retinoic acid receptor (RAR) and signal transducer and activator of transcription 1 (STAT1) bind to rs57217136. Conclusion Both LDLR rs6511720 and rs57217136 are functional variants. Both these minor alleles create enhancer-binding protein sites for TFs and may contribute to increased LDLR expression, which is consequently associated with reduced

  16. TERT Polymorphism rs2736100-C Is Associated with EGFR Mutation-Positive Non-Small Cell Lung Cancer

    PubMed Central

    Zheng, Yonglan; Niu, Xiaomin; Weng, Xiaoling; Zhang, Hong; Favus, Murray; Zhang, Lanjun; Jia, Weihua; Zeng, Yixin; Amos, Christopher I; Lu, Shun; Wang, Hui-Yun; Liu, Yun; Liu, Wanqing

    2015-01-01

    Purpose Epidermal growth factor receptor (EGFR) mutation-positive (EGFRmut+) non-small cell lung cancer (NSCLC) may be a unique orphan disease. Previous studies suggested that the telomerase reverse transcriptase (TERT) gene polymorphism is associated with demographic and clinical features strongly associated with EGFR mutations, e.g. adenocarcinoma histology, never-smoking history and female gender. We aim to test the association between TERT polymorphism and EGFRmut+ NSCLC. Experimental Design We conducted a genetic association study in Chinese NSCLC patients (n=714) and healthy controls (n=2,520), between the rs2736100 polymorphism and EGFRmut+ NSCLC. We further tested the association between the EGFR mutation status and mean leukocyte telomere length (LTL). The potential function of rs2736100 in lung epithelial cells was also explored. Results The rs2736100-C allele was significantly associated with EGFRmut+ NSCLC (OR=1.52, 95%CI=1.28–1.80, p=1.6×10−6) but not EGFRmut− NSCLC (OR=1.07, 95%CI=0.92–1.24, p=0.4). While NSCLC patients as a whole have significantly longer LTL compared to healthy controls (p≤10−13), the EGFRmut+ patients have even longer LTL compared to EGFRmut-patients (p=0.008). Meanwhile, rs2736100 was significantly associated with TERT mRNA expression in both normal and tumor lung tissues. All results remained significant after controlling for age, gender, smoking status and histology (p<0.05 for all tests). Moreover, the rs2736100 DNA sequence has an allele-specific affinity to nuclear proteins extracted from lung epithelial cells, which led to an altered enhancer activity of the sequence in vitro. Conclusion Our study suggests that telomerase and telomere function may be essential for carcinogenesis of EGFRmut+ NSCLC. Further investigation for the underlying mechanism is warranted. PMID:26149460

  17. Polymorphism of rs7688672 and rs10033237 in cGKII/PRKG2 and gout susceptibility of Han population in northern China.

    PubMed

    Guo, Min; Cheng, Zhifeng; Li, Changgui; Li, Shanshan; Li, Ming; Wang, Mingli; Xu, Jinmei; Tang, Yingying; Wang, Yujing; Qiu, Wenli; Liu, Xiaomin

    2015-05-10

    Gout is a genetic or acquired metabolic disease caused by increase of uric acid synthesis resulted from purine metabolic abnormalities. Whether cGMP-dependent protein kinase 2 (cGKII/PRKG2) is correlated with gout remains controversial. The objective of the present study was to investigate whether there is a correlation between polymorphism of cGKII/PRKG2 and gout susceptibility of Han population in northern China. Four hundred and five male patients with gout in the case group and 429 controls in the control group were collected from the Department of Endocrinology and Metabolic Disease, the Fourth Affiliated Hospital of Harbin Medical University. A case-control study method was used to study the correlation between cGKII/PRKG2 polymorphism rs7688672 and rs10033237 and gout susceptibility. The genotype frequencies of rs7688672 and rs10033237 polymorphisms of cGKII/PRKG2 in the case group and the control group both were in accordance with Hardy-Weinberg equilibrium. There were significant differences of rs10033237 in the allele frequencies and genotype distributions (P<0.05) between the two groups, while no association was found between rs7688672 and gout. Combined mutation sites AA(*) from rs7688672 and rs10033237 were negatively correlated with gout susceptibility, whereas haplotype GG(*) was positively correlated with gout susceptibility. In conclusion, patients with rs10033237 polymorphism of cGKII/PRKG2 gene are more likely to suffer from gout. With regard to haplotypes of rs10033237 and rs7688672, both AA(*) and GG(*) are related to gout. AA(*) is a gout susceptible gene, whereas GG(*) is a protective gene.

  18. Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population

    PubMed Central

    Zhang, Junlong; Zhan, Wenli; Yang, Bin; Tian, Anning; Chen, Lin; Liao, Yun; Wu, Yongkang; Cai, Bei; Wang, Lanlan

    2017-01-01

    Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+ T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 of HLA-DP and SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60–0.91, P = 0.004; rs9277535, OR = 0.72, 95%CI = 0.59–0.88, P = 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P = 0.037, P = 0.020 and P = 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion, HLA-DP polymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients. PMID:28094303

  19. Evolved expendable launch vehicle system: RS-68 main engine development

    NASA Astrophysics Data System (ADS)

    Conley, David; Lee, Norman Y.; Portanova, Peter L.; Wood, Byron K.

    2003-08-01

    Delta IV is one of two competing Evolved Expendable Launch Vehicle (EELV) systems being developed in an industry/United States Government partnership to meet the needs of the new era of space launch for the early decades of the 21 st Century. The Rocketdyne Division of The Boeing Company and the United States Air Force have developed a 650 Klbf sea-level (2.9 MN) class liquid hydrogen/liquid oxygen main engine for the Delta IV family of EELV. The purpose of this paper is to present the innovative approach to the design, development, testing and certification of the RS-68 engine.

  20. RS INDI - A photometric analysis using the grid technique

    NASA Astrophysics Data System (ADS)

    Marton, S. F.; Grieco, A.; Lapasset, E.; Sistero, R. F.; Claria, J. J.

    1990-10-01

    Simultaneous solutions from 2484 UBV photelelectric observations of the EB-type system RS Indi has been obtained with the Wilson-Devinney code. Using the grid technique, families of solutions were found for all possible configurations. As different configurations gave similar quality of fit, the more probable configuration was suggested by physical criteria. New times of minimum light obtained in the years 1985 and 1986 confirm the decreasing period of the system. No interpretation was found for the asymmetries observed in the light curves.

  1. SEAC4RS Aerosol Radiative Effects and Heating Rates

    NASA Astrophysics Data System (ADS)

    Cochrane, S.; Schmidt, S.; Redemann, J.; Hair, J. W.; Ferrare, R. A.; Segal-Rosenhaimer, M.; LeBlanc, S. E.

    2015-12-01

    We will present (a) aerosol optical properties, (b) aerosol radiative forcing, (c) aerosol and gas absorption and heating rates, and (d) spectral surface albedo for cases from August 19th and 26th of the SEAC4RS mission. This analysis is based on irradiance data from the Solar Spectral Flux Radiometer (SSFR), spectral aerosol optical depth from the Sky-Scanning, Sun-Tracking Atmospheric Research (4STAR), and extinction profiles from the DIAL/High Spectral Resolution Lidar (HSRL). We derive spectrally resolved values of single scattering albedo, asymmetry parameter, and surface albedo from the data, and determine profiles of absorption and heating rate segregated by absorber (aerosol and gas).

  2. [Medication adherence of elderly in Porto Alegre, RS].

    PubMed

    Rocha, Cristiane Hoffmeister; de Oliveira, Ana Paula Sueiro; Ferreira, Caroline; Faggiani, Fabiana Tôrres; Schroeter, Guilherme; de Souza, Antônio Carlos Araújo; DeCarli, Geraldo Attilio; Morrone, Fernanda Bueno; Werlang, Maria Cristina

    2008-04-01

    Polipharmacy and medication non-adherence are problems faced frequently in the treatment of elderly patients. An exploratory cross-sectional study and quantitative approach were conducted to assess the frequency of treatment-adherence in elderly and how polipharmacy can affect adherence. Four hundred and sixty six elderly answered a questionnaire in Porto Alegre, RS in individual interviews. The adherence frequency found was 173 (37.1%) and was higher among those, who use less medication. These results indicate the need for implementing educational programs for the elderly in order to help them to follow their drug therapy.

  3. Anti-solar differential rotation on the active sub-giant HU Virginis

    NASA Astrophysics Data System (ADS)

    Harutyunyan, G.; Strassmeier, K. G.; Künstler, A.; Carroll, T. A.; Weber, M.

    2016-08-01

    Context. Measuring surface differential rotation (DR) on different types of stars is important when characterizing the underlying stellar dynamo. It has been suggested that anti-solar DR laws can occur when strong meridional flows exist. Aims: We aim to investigate the differential surface rotation on the primary star of the RS CVn binary, HU Vir, by tracking its starspot distribution as a function of time. We also aim to recompute and update the values for several system parameters of the triple system HU Vir (close and wide orbits). Methods: Time-series high-resolution spectroscopy for four continuous months was obtained with the 1.2-m robotic STELLA telescope. Nine consecutive Doppler images were reconstructed from these data, using our line-profile inversion code iMap. An image cross-correlation method was applied to derive the surface differential-rotation law for HU Vir. New orbital elements for the close and the wide orbits were computed using our new STELLA radial velocities (RVs) combined with the RV data available in the literature. Photometric observations were performed with the Amadeus Automatic Photoelectric Telescope (APT), providing contemporaneous Johnson-Cousins V and I data for approximately 20 yrs. This data was used to determine the stellar rotation period and the active longitudes. Results: We confirm anti-solar DR with a surface shear parameter α of -0.029 ± 0.005 and -0.026 ± 0.009, using single-term and double-term differential rotation laws, respectively. These values are in good agreement with previously claimed results. The best fit is achieved assuming a solar-like double-term law with a lap time of ≈400 d. Our orbital solutions result in a period of 10.387678 ± 0.000003 days for the close orbit and 2726 ± 7 d (≈7.5 yr) for the wide orbit. A Lomb-Scarge (L-S) periodogram of the pre-whitened V-band data reveals a strong single peak providing a rotation period of 10.391 ± 0.008 d, well synchronized to the short orbit. Based on

  4. Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele.

    PubMed

    Kiive, Evelyn; Laas, Kariina; Vaht, Mariliis; Veidebaum, Toomas; Harro, Jaanus

    2017-02-23

    Research of GABRA2 gene in alcohol use and impulse control suggests its role in aggressive behaviour. The purpose of the present study was to examine the effects of GABRA2 genotype and stressful life events on aggressive behaviour, alcohol use frequency and occurrence of alcohol use disorder in a population representative sample of adolescents followed up from third grade to 25 years of age. The sample consisted of the younger cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study. Aggressive behaviour was rated with the activity scale of af Klinteberg, Illinois Bully Scale and Buss-Perry Aggression Questionnaire. Stressful life events and alcohol use were self-reported. Life history of aggression and lifetime occurrence of psychiatric disorders were estimated in a structured interview. The sample was genotyped for GABRA2 rs279826 and rs279858 polymorphisms that are in strong linkage disequilibrium and yielded very similar findings: Higher number of stressful life events reported at age 15 was associated with increased fighting in A-allele carriers, but not in GG homozygotes. At age 25, A-allele carriers with more stressful life events scored higher on physical aggression than those with less stress, and this was also observed regarding life history of aggression. A-allele carriers exposed to higher stress had consumed alcoholic beverages more frequently at age 15, and by age 25, they had alcohol use disorder with higher prevalence. The results of the present study suggest that the GABRA2 genotype interacts with stress in young people with impact on the development of alcohol use and aggressive behaviour.

  5. Role of IL-8 rs4073 and rs2227306 polymorphisms in the development of primary gouty arthritis in a Chinese population.

    PubMed

    Cui, Y X; Zhao, H; Guo, H Q

    2016-10-17

    In this study, we investigated the role of two single nucleotide polymorphisms in the promoter region of the interleukin-8 gene (IL-8; rs4073 and rs2227306) in the susceptibility to primary gouty arthritis in a Chinese population. Three hundred and twelve patients with primary gouty arthritis and 340 healthy controls were recruited from the Yan'an University Affiliated Hospital between January 2014 and March 2015. The IL-8 rs4073 and rs2227306 polymorphisms were genotyped by polymerase chain reaction combined with restriction fragment length polymorphism. Unconditional multiple-logistic regression analysis revealed that the TT genotype of rs4073 was correlated with primary gouty arthritis risk, compared to the AA genotype [adjusted odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.08-2.54; P = 0.02]. In addition, the IL-8 rs4073 T allele was associated with a significant elevated risk of primary gouty arthritis, in comparison to the A allele (OR = 1.34, 95%CI = 1.07-1.67; P = 0.01). However, we observed no significant relationship between the IL-8 rs2227306 polymorphism and primary gouty arthritis risk. The results of this study suggest that the IL-8 rs4073 polymorphism could be a marker for primary gouty arthritis development.

  6. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4...-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate as follows: (2) In or on food commodities in food handling establishments where food and food products are held, processed, prepared...

  7. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4...-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate as follows: (2) In or on food commodities in food handling establishments where food and food products are held, processed, prepared...

  8. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4...-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate as follows: (2) In or on food commodities in food handling establishments where food and food products are held, processed, prepared...

  9. The relationship between toll like receptor 4 gene rs4986790 and rs4986791 polymorphisms and sepsis susceptibility: A meta-analysis

    PubMed Central

    Liu, Rui; Mo, Yuan-Yuan; Wang, Hui-Li; Tan, Yan; Wen, Xiu-Jie; Deng, Man-Jing; Yan, Hong; Li, Lei

    2016-01-01

    Accumulating evidences have demonstrated that lipopolysaccharide (LPS) represents the important etiologic factor for sepsis. Some previous studies have reported the relationship between common polymorphisms rs4986790 and rs4986791 in the coding gene for this receptor and the susceptibility to sepsis, but there were distinct divergences between those findings. We therefore designed this meta-analysis incorporated 28 published articles containing 6,537 sepsis patients and 8,832 controls for a more comprehensive conclusion on this matter. Odds ratios (ORs) and 95% confidence interval (95% CIs) were calculated to evaluate the association of toll like receptor 4 gene polymorphisms rs4986790 and rs4986791 with sepsis risk. Heterogeneity between included studies was inspected using Q test, and sensitivity analysis was implemented via sequential deletion of each included study to investigate the stability of overall estimates. Funnel plot and Egger’s test were adopted to examine publication bias across selected studies. We found no significant association for either the polymorphism rs4986790 or rs4986791 with sepsis susceptibility in total analysis under any genetic models. Neither did we after combining these two polymorphisms. The results of this meta-analysis suggest that the rs4986790 and rs4986791 polymorphisms in toll like receptor 4 gene may have no statistically significant influence on sepsis susceptibility. PMID:27958344

  10. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency

    PubMed Central

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y. Eugene; Zhang, Jifeng

    2016-01-01

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells. PMID:26817820

  11. RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency.

    PubMed

    Song, Jun; Yang, Dongshan; Xu, Jie; Zhu, Tianqing; Chen, Y Eugene; Zhang, Jifeng

    2016-01-28

    Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.

  12. Electrochemical evaluation of the interaction between ascorbic acid and the cardiotonic drug RS-82856.

    PubMed

    Visor, G C; Lin, L H; Kenley, R A; Venuti, M C; Alvarez, R

    1987-12-01

    The solution phase interaction between ascorbic acid and the cardiotonic drug N-cyclohexyl-N-methyl-4(7-oxy 1,2,3,5-tetrahydroimidazol[2,1-b] quinazolin-2-one butyramide (RS-82856) was evaluated using a differential pulse voltammetric technique. Shifts in the peak potential of ascorbic acid to higher energy as well as decreases in peak current values were monitored as a function of RS-82856 concentration. The electrochemical data were obtained under conditions where both the drug and the ascorbic acid concentrations exhibited linear relationships with peak current values. The methodology was extended to the study of two other structurally related phosphodiesterase inhibitors cilostamide and anagrelide. The complexation of these drugs with ascorbic acid were also characterized by decreases in the diffusion currents of ascorbic acid as well as by anodic shifts in the peak potential. The significance of these observations may be related to the inhibition of cyclic nucleotide phosphodiesterase activity by both the drugs tested and the ascorbic acid.

  13. The FTO rs9939609 and LEPR rs1137101 mothers–newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns

    PubMed Central

    Mărginean, Claudiu; Mărginean, Cristina Oana; Iancu, Mihaela; Meliţ, Lorena Elena; Tripon, Florin; Bănescu, Claudia

    2016-01-01

    Abstract The aim of this study was to assess the impact of mothers’ and newborns’ fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs1137101 gene polymorphisms on neonatal anthropometric parameters in order to identify a potential risk for developing obesity. We performed a cross-sectional study on 355 mother–newborn couples in an Obstetrics Gynecology Tertiary Hospital from Romania, evaluated with regard to anthropometric parameters, clinical and laboratory parameters besides 2 genetic polymorphisms (FTO rs9939609 and LEPR rs1137101). Newborns with mothers carrying variant AT or AA genotype for FTO rs9939609 presented lower BMI (P = 0.012) and lower MUAC (P = 0.029). There was a significant interaction effect between newborn and mother LEPR rs1137101 polymorphism on birth weight (P = 0.009) and BMI (P = 0.007). We noticed significantly increased birth weight and BMI in newborns carriers of AG + GG genotype, coming from mothers with AA genotype (P = 0.006). There was no evidence of significant interaction effect between newborn and mother FTO rs9939609 polymorphism on the studied anthropometrical data (P > 0.05). In addition, lower BMI scores (P = 0.042) were observed in newborns carriers of TT genotype whose mothers had AA + AT genotype. Lower MUAC scores (P = 0.041) were noticed in newborns carriers of AA + AT genotype whose mothers had AA + AT genotype for FTO rs9939609 gene polymorphism. Newborns carriers of the AG + GG genotype (P = 0.003) of LEPR rs1137101 coming from mothers with increased FMI (upper tertile) had significantly increased BMIs. Presence of the variant A allele of FTO rs9939609 polymorphism in mothers decreased BMI and MUAC in newborns. The impact of LEPR rs1137101 polymorphism on BMI and birth weight in newborns differed depending on the presence/absence of the dominant LEPR allele in mothers. In addition, we noticed that maternal FMI presented a significant positive effect on

  14. Contemporary Pharyngeal and Invasive emm1 and Invasive emm12 Group A Streptococcus Isolates Exhibit Similar In Vivo Selection for CovRS Mutants in Mice

    PubMed Central

    Feng, Wenchao; Liu, Mengyao; Chen, Daniel G.; Yiu, Rossana; Fang, Ferric C.; Lei, Benfang

    2016-01-01

    Group A Streptococcus (GAS) causes diverse infections ranging from common pharyngitis to rare severe invasive infections. Invasive GAS isolates can have natural mutations in the virulence regulator CovRS, which result in enhanced expression of multiple virulence genes, suppressed the expression of the protease SpeB, and increased virulence. It is believed that CovRS mutations arise during human infections with GAS carrying wild-type CovRS and are not transmissible. CovRS mutants of invasive GAS of the emm1 genotype arise readily during experimental infection in mice. It is possible that invasive GAS arises from pharyngeal GAS through rare genetic mutations that confer the capacity of mutated GAS to acquire covRS mutations during infection. The objective of this study was to determine whether contemporary pharyngeal emm1 GAS isolates have a reduced propensity to acquire CovRS mutations in vivo compared with invasive emm1 GAS and whether emm3, emm12, and emm28 GAS acquire CovRS mutants in mouse infection. The propensity of invasive and pharyngeal emm1 and invasive emm3, emm12, and emm28 SpeBA+ isolates to acquire variants with the SpeBA- phenotype was determined during subcutaneous infection of mice. The majority of both invasive and pharyngeal emm1 SpeBA+ isolates and two of three emm12 isolates, but not emm3 and emm28 isolates, were found to acquire SpeBA- variants during skin infection in mice. All analyzed SpeBA- variants of emm1 and emm12 GAS from the mouse infection acquired covRS mutations and produced more platelet-activating factor acetylhydrolase SsE. Thus, contemporary invasive and pharyngeal emm1 GAS isolates and emm12 GAS have a similar capacity to acquire covRS mutations in vivo. The rarity of severe invasive infections caused by GAS does not appear to be attributable to a reduced ability of pharyngeal isolates to acquire CovRS mutations. PMID:27611332

  15. VIIRS Aerosol Products During the SEAC4RS Field Experiment

    NASA Astrophysics Data System (ADS)

    Remer, L. A.; Munchak, L. A.; Huang, J.; Martins, J. V.; Espinosa, R.; Orozco, D.

    2014-12-01

    The Studies of Emissions, Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field experiment that took place during August and September 2013 offered an in depth portrait of the aerosol system over much of the continental United States. Heavily instrumented aircraft, including the NASA DC-8 sampled a wide variety of aerosol types including transported Saharan dust, both fresh and aged smoke from western wildfires, urban pollution plumes and also biogenic aerosol produced by the "green volcano" in the vegetated Ozarks. Complementing these aircraft measurements was an enhanced array of AERONET stations sprinkled across the country and also concentrated in a mesoscale array near the home base of Houston Texas. This rich collection of suborbital aerosol information permits a more comprehensive evaluation of the VIIRS aerosol product that includes validation of the products across the mesoscale and choices of case studies in which we can delve deeper into the VIIRS retrieval to test algorithm assumptions. We will compare VIIRS retrievals during SEAC4RS with MODIS retrievals, with AERONET observations and retrievals, and with measurements and retrievals from the Polar Imaging Nephelometer (PI-Neph) that flew aboard the NASA DC-8.

  16. Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146a rs2910164) and breast cancer risk: a meta-analysis

    PubMed Central

    Zhang, Hong; Zhang, Yafei; Yan, Wanjun; Wang, Wen; Zhao, Xixi; Ma, Xingcong; Gao, Xiaoyan; Zhang, Shuqun

    2017-01-01

    Three functional microRNA polymorphisms (miR-499 rs3746444 A > G, miR-196a rs11614913 C > T and miR-146a rs2910164 G > C) have been reported to be associated with breast cancer (BC) risk. However, the results of the published studies are inconsistent. In order to obtain a more credible result, we conducted this meta-analysis. We searched PubMed, EMBASE and Web of Science databases to identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Thirty-eight eligible studies with 17,417 cases and 18,988 controls were included in this meta-analysis. Our results showed that the rs3746444 was associated with an increased breast cancer risk in the four genetic models (G vs. A: OR = 1.17, P = 0.008; GG vs. AA: OR = 1.41, P < 0.001; AG vs. AA: OR = 1.10, P = 0.036; GG+AG vs. AA: OR = 1.16, P = 0.001). In the subgroup analysis by ethnicity, significant correlation remained in Asians but not in Caucasians. For rs11614913, obvious decreased breast cancer risk was observed in Caucasian populations (T vs. C: OR = 0.93, P = 0.044). However, we couldn't detect an association between rs2910164 and breast cancer risk. This meta-analysis demonstrates that rs3746444 could increase breast cancer risk in Asians and in general populations, while rs11614913 could decrease the risk of breast cancer in Caucasians. The rs2910164 polymorphism has no association with breast cancer risk. More multicenter studies with larger sample sizes are required to verify our results. PMID:27880723

  17. Impact of G-quadruplex structures and intronic polymorphisms rs17878362 and rs1642785 on basal and ionizing radiation-induced expression of alternative p53 transcripts

    PubMed Central

    Perriaud, Laury; Marcel, Virginie; Sagne, Charlotte; Favaudon, Vincent; Guédin, Aurore; De Rache, Aurore; Guetta, Corinne; Hamon, Florian; Teulade-Fichou, Marie-Paule; Hainaut, Pierre; Mergny, Jean-Louis; Hall, Janet

    2014-01-01

    G-quadruplex (G4) structures in intron 3 of the p53 pre-mRNA modulate intron 2 splicing, altering the balance between the fully spliced p53 transcript (FSp53, encoding full-length p53) and an incompletely spliced transcript retaining intron 2 (p53I2 encoding the N-terminally truncated Δ40p53 isoform). The nucleotides forming G4s overlap the polymorphism rs17878362 (A1 wild-type allele, A2 16-base pair insertion) which is in linkage disequilibrium with rs1642785 in intron 2 (c.74+38 G>C). Biophysical and biochemical analyses show rs17878362 A2 alleles form similar G4 structures as A1 alleles although their position is shifted with respect to the intron 2 splice acceptor site. In addition basal FSp53 and p53I2 levels showed allele specific differences in both p53-null cells transfected with reporter constructs or lymphoblastoid cell lines. The highest FSp53 and p53I2 levels were associated with combined rs1642785-GG/rs17878362-A1A1 alleles, whereas the presence of rs1642785-C with either rs17878362 allele was associated with lower p53 pre-mRNA, total TP53, FSp53 and p53I2 levels, due to the lower stability of transcripts containing rs1642785-C. Treatment of lymphoblastoid cell with the G4 binding ligands 360A or PhenDC3 or with ionizing radiation increased FSp53 levels only in cells with rs17878362 A1 alleles, suggesting that under this G4 configuration full splicing is favoured. These results demonstrate the complex effects of intronic TP53 polymorphisms on G4 formation and identify a new role for rs1642785 on mRNA splicing and stability, and thus on the differential expression of isoform-specific transcripts of the TP53 gene. PMID:25269805

  18. Dual regulation of inaA by the multiple antibiotic resistance (mar) and superoxide (soxRS) stress response systems of Escherichia coli.

    PubMed Central

    Rosner, J L; Slonczewski, J L

    1994-01-01

    The roles of the marRAB (multiple antibiotic resistance) operon and soxRS (superoxide response) genes in the regulation of inaA, an unlinked weak-acid-inducible gene, were studied. inaA expression was estimated from the beta-galactosidase activity of a chromosomal inaA1::lacZ transcriptional fusion. marR mutations that elevate marRAB transcription and engender multiple antibiotic resistance elevated inaA expression by 10- to 20-fold over that of the wild-type. Similarly, one class of inaA constitutive mutants that mapped to the mar region were multiply antibiotic resistant. Overexpression of marA alone on a multicopy plasmid caused high constitutive expression of inaA in a strain with an extensive (39-kbp) marRAB deletion. Salicylate, an inducer of marRAB and of an unidentified mar-independent antibiotic resistance system, induced inaA by 6-fold. A portion of this induction was also mar independent. Two soxRS constitutive mutants that were tested showed elevated levels of inaA. Paraquat, an inducer of the soxRS system, elevated inaA expression by 6- to 9-fold. This induction was soxRS dependent and not mar dependent, whereas induction of inaA by salicylate was not dependent on soxRS. Paraquat induced resistance to norfloxacin in the mar-deleted strain but not in a soxRS-deleted strain. Thus, induction of multiple antibiotic resistance and inaA by salicylate occurs via mar and an unidentified pathway, while induction by paraquat occurs via soxRS. PMID:7928997

  19. Film coating of seeds with Bacillus cereus RS87 spores for early plant growth enhancement.

    PubMed

    Jetiyanon, Kanchalee; Wittaya-Areekul, Sakchai; Plianbangchang, Pinyupa

    2008-10-01

    The plant growth-promoting rhizobacterium Bacillus cereus RS87 was previously reported to promote plant growth in various crops in both greenhouse and field trials. To apply as a plant growth promoting agent with practical use, it is essential to ease the burden of routine preparation of a fresh suspension of strain RS87 in laboratory. The objectives of this study were to investigate the feasibility of film-coating seeds with B. cereus RS87 spores for early plant growth enhancement and to reveal the indoleacetic acid (IAA) production released from strain RS87. The experiment consisted of the following 5 treatments: nontreated seeds, water-soaked seeds, film-coated seeds, seeds soaked with vegetative cells of strain RS87, and film-coated seeds with strain RS87 spores. Three experiments were conducted separately to assess seed emergence, root length, and plant height. Results showed that both vegetative cells and spores of strain RS87 significantly promoted (P < or = 0.05) seed emergence, root length and plant height over the control treatments. The strain RS87 also produced IAA. In conclusion, the film coating of seeds with spores of B. cereus RS87 demonstrated early plant growth enhancement as well as seeds using their vegetative cells. IAA released from strain RS87 would be one of the mechanisms for plant growth enhancement.

  20. Remitting seronegative symmetrical synovitis with pitting edema (RS3PE); a rare association with phyllodes tumour of breast.

    PubMed

    Sarkar, R N; Phaujdar, Sibaji; Banerjee, Siwalik; Siddhanta, Sattik; De, Dibyendu; Bhattachary, Kuntal; Pal, Hare Krishna

    2012-04-01

    Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare entity mainly found in elderly males. It is characterized by pitting edema mainly of dorsum of both hands giving a "boxing glove hand" appearance; rarely involving feet also, acute in onset, negative rheumatoid factor and a good response to low dose corticosteroid therapy. Clinically it almost resembles a case of polymyalgia rheumatica, late onset rheumatoid arthritis or other seronegative spondyloarthropathy.Though there are multiple underlying factors causing this rare entity but it has very close associations with many malignancies.So far its association with solid tumours and hematological malignancies has been reported. Phyllodes tumour of breast shows wide spectrum of activity from a benign condition to a locally aggressive and sometimes metastatic tumour.One fourth of the cases recur after definitive treatment.Our case represent an unusual association with recurrent phyllodes tumour of breast with RS3PE.

  1. Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs

    PubMed Central

    Torres, Adrian G.; Fabani, Martin M.; Vigorito, Elena; Williams, Donna; Al-Obaidi, Naowras; Wojciechowski, Filip; Hudson, Robert H. E.; Seitz, Oliver; Gait, Michael J.

    2012-01-01

    Anti-miRs are oligonucleotide inhibitors complementary to miRNAs that have been used extensively as tools to gain understanding of specific miRNA functions and as potential therapeutics. We showed previously that peptide nucleic acid (PNA) anti-miRs containing a few attached Lys residues were potent miRNA inhibitors. Using miR-122 as an example, we report here the PNA sequence and attached amino acid requirements for efficient miRNA targeting and show that anti-miR activity is enhanced substantially by the presence of a terminal-free thiol group, such as a Cys residue, primarily due to better cellular uptake. We show that anti-miR activity of a Cys-containing PNA is achieved by cell uptake through both clathrin-dependent and independent routes. With the aid of two PNA analogues having intrinsic fluorescence, thiazole orange (TO)-PNA and [bis-o-(aminoethoxy)phenyl]pyrrolocytosine (BoPhpC)-PNA, we explored the subcellular localization of PNA anti-miRs and our data suggest that anti-miR targeting of miR-122 may take place in or associated with endosomal compartments. Our findings are valuable for further design of PNAs and other oligonucleotides as potent anti-miR agents. PMID:22070883

  2. Creative Implementation of 3Rs Principles within Industry Programs: Beyond Regulations and Guidelines

    PubMed Central

    Bratcher, Natalie A; Reinhard, Gregory R

    2015-01-01

    The industry involved with using animals as an essential part of research has supported the theory and philosophy of the 3Rs for years. However, both the culture and approach surrounding the 3Rs is evolving rapidly, and many institutions are attempting to surpass the regulations and guidelines to implement the 3Rs for improved science and animal welfare. Regulatory documents and guidelines such as the Animal Welfare Act, the Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training clearly outline how the IACUC should address the 3Rs, but there are many additional paradigms and resources that an institution can use to promote the 3Rs creatively. We review the legal mandates and guidelines that institutions must or should follow, and we present some creative approaches toward their compliance, including the creation of full-time dedicated 3Rs roles as well as temporary 3Rs-focused positions such as visiting scientist and postdoctoral fellowships and internships. We also discuss how to creatively achieve 3Rs progress through internal committees and working groups, involvement in 3Rs consortia, recognizing 3Rs advances through awards programs, and creating 3Rs volunteer opportunities. Adherence to regulations and guidelines creates a solid foundation for good animal care and science, and creative 3Rs approaches enable the growth of a robust animal welfare culture that enhances the potential for 3Rs benefits to animals and science. PMID:25836958

  3. Creative implementation of 3Rs principles within industry programs: beyond regulations and guidelines.

    PubMed

    Bratcher, Natalie A; Reinhard, Gregory R

    2015-03-01

    The industry involved with using animals as an essential part of research has supported the theory and philosophy of the 3Rs for years. However, both the culture and approach surrounding the 3Rs is evolving rapidly, and many institutions are attempting to surpass the regulations and guidelines to implement the 3Rs for improved science and animal welfare. Regulatory documents and guidelines such as the Animal Welfare Act, the Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and the US Government Principles for the Utilization and Care of Vertebrate Animals Used in Testing, Research, and Training clearly outline how the IACUC should address the 3Rs, but there are many additional paradigms and resources that an institution can use to promote the 3Rs creatively. We review the legal mandates and guidelines that institutions must or should follow, and we present some creative approaches toward their compliance, including the creation of full-time dedicated 3Rs roles as well as temporary 3Rs-focused positions such as visiting scientist and postdoctoral fellowships and internships. We also discuss how to creatively achieve 3Rs progress through internal committees and working groups, involvement in 3Rs consortia, recognizing 3Rs advances through awards programs, and creating 3Rs volunteer opportunities. Adherence to regulations and guidelines creates a solid foundation for good animal care and science, and creative 3Rs approaches enable the growth of a robust animal welfare culture that enhances the potential for 3Rs benefits to animals and science.

  4. The CroRS Two-Component Regulatory System Is Required for Intrinsic β-Lactam Resistance in Enterococcus faecalis

    PubMed Central

    Comenge, Yannick; Quintiliani, Richard; Li, Ling; Dubost, Lionnel; Brouard, Jean-Paul; Hugonnet, Jean-Emmanuel; Arthur, Michel

    2003-01-01

    Enterococcus faecalis produces a specific penicillin-binding protein (PBP5) that mediates high-level resistance to the cephalosporin class of β-lactam antibiotics. Deletion of a locus encoding a previously uncharacterized two-component regulatory system of E. faecalis (croRS) led to a 4,000-fold reduction in the MIC of the expanded-spectrum cephalosporin ceftriaxone. The cytoplasmic domain of the sensor kinase (CroS) was purified and shown to catalyze ATP-dependent autophosphorylation followed by transfer of the phosphate to the mated response regulator (CroR). The croR and croS genes were cotranscribed from a promoter (croRp) located in the rrnC-croR intergenic region. A putative seryl-tRNA synthetase gene (serS) located immediately downstream from croS did not appear to be a target of CroRS regulation or to play a role in ceftriaxone resistance. A plasmid-borne croRp-lacZ fusion was trans-activated by the CroRS system in response to the presence of ceftriaxone in the culture medium. The fusion was also induced by representatives of other classes of β-lactam antibiotics and by inhibitors of early and late steps of peptidoglycan synthesis. The croRS null mutant produced PBP5, and expression of an additional copy of pbp5 under the control of a heterologous promoter did not restore ceftriaxone resistance. Deletion of croRS was not associated with any defect in the synthesis of the nucleotide precursor UDP-MurNAc-pentapeptide or of the d-Ala4→l-Ala-l-Ala-Lys3 peptidoglycan cross-bridge. Thus, the croRS mutant was susceptible to ceftriaxone despite the production of PBP5 and the synthesis of wild-type peptidoglycan precursors. These observations constitute the first description of regulatory genes essential for PBP5-mediated β-lactam resistance in enterococci. PMID:14645279

  5. Relationships between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men – a preliminary study

    PubMed Central

    Rotter, Iwona; Skonieczna-Żydecka, Karolina; Kosik-Bogacka, Danuta; Adler, Grażyna; Rył, Aleksandra; Laszczyńska, Maria

    2016-01-01

    Purpose Metabolic disorders, including MetS, obesity, and lipid disorders, may be related to genetic factors. Metabolic disorders are associated with decreased TS levels in aging men. The aim of this study was to evaluate the relationship between FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms and the presence of MetS and its components, the concurrent lipid disorders, as well as sex hormone concentrations. Subjects and methods This study involved 272 men of Caucasian descent aged 50–75 years. Lipid profile, including TCh, LDL, HDL, and TG, was evaluated by spectrophotometric method. Anthropometric measurements concerned WC and blood pressure. MetS was diagnosed according to the criteria of the IDF. Sex hormone profile, including TST, FTS, E2, DHEAS, and SHBG, was examined using enzyme-linked immunosorbent assay. Polymorphisms within FTO, MC4R, and PPARγ genes were identified using polymerase chain reaction-restriction fragments length polymorphism. Results This study did not show links between the analyzed genetic polymorphisms and the presence of MetS, T2DM, HT, and obesity. However, higher concentrations of TCh and LDL were found in men with the FTO rs9939609 polymorphism in the recessive mode of inheritance (P=0.03 and P=0.05, respectively). Lower WC was found to be associated with MC4R rs17782313 gene inherited in the same model (P=0.005). Conclusion FTO rs9939609, MC4R rs17782313, and PPARγ rs1801282 polymorphisms seem to have little effect on the incidence of metabolic malfunctions and no effect on androgen-related disorders in the examined middle-aged and elderly men. PMID:27920511

  6. Family-Based Association Study of rs17300539 and rs12495941 Polymorphism in Adiponectin Gene and Polycystic Ovary Syndrome in a Chinese Population

    PubMed Central

    Sun, Xianchang; Wu, Xingguo; Duan, Yunmin; Liu, Guanghai; Yu, Xinyan; Zhang, Wenjuan

    2017-01-01

    Backgriond Polycystic ovary syndrome (PCOS) is a complex disease that has both genetic and environmental components. Adiponectin plays an important role in the regulation of insulin sensitivity and insulin resistance (IR) in PCOS. The aim of this study was to determine 2 single-nucleotide polymorphisms (SNPs) variants (rs12495941 and rs17300539) of the adiponectin gene (ADIPOQ) in polycystic ovary syndrome (PCOS) families. Material/Methods We recruited 197 PCOS probands, their biological parents, and 192 controls. Anthropometric variables, including hip circumference (HC) and waist circumference (WC), were measured in all subjects during their first visit to the outpatient department. Serum T, FBG, FINS, TC, TG, LDL, and HDL levels were measured. PCOS patients were divided into 2 groups based on BMI: group A (BMI <25 kg/m2) and group B (BMI ≥25 kg/m2). Parents of PCOS were accordingly categorized into group C and group D (fathers), and group E and group F (mothers). The associations among ADIPOQ rs12495941, rs17300539, and PCOS were analyzed using the transmission disequilibrium test (TDT). Results A significant association was found between SNP rs17300539 and PCOS in our Chinese population. The levels of TG and FINS and the genotype frequencies of rs17300539 are significantly different between overweight and lean PCOS. No significant association was detected for rs12495941. Conclusions TDT confirms that rs17300539 of ADIPOQ is strongly associated with the risk of PCOS in a Chinese Han population, but rs12495941 of ADIPOQ is not associated with the occurrence of PCOS. PMID:28060790

  7. Interleukin-28B rs12979860C/T and rs8099917T/G contribute to spontaneous clearance of hepatitis C virus in Caucasians.

    PubMed

    Zheng, Ming-Hua; Li, Yu; Xiao, Dong-Dong; Shi, Ke-Qing; Fan, Yu-Chen; Chen, Li-Li; Liu, Wen-Yue; Luo, Ying-Wan; Chen, Yong-Ping

    2013-04-15

    Two single nucleotide polymorphisms rs12979860C/T and rs8099917T/G around interleukin-28B (IL28B) locus have been extensively investigated in their association with hepatitis C virus (HCV) spontaneous clearance. However, with the variable and even inconsistent results, it is necessary to conduct a meta-analysis. A literature search was conducted to seek articles about genetic variation of IL28B and spontaneous clearance of HCV. Odds ratio with 95% confidential interval were calculated to estimate their relationship. Furthermore, meta-regression analysis was performed to search for potential affective factors. A total of 8 studies including 2460 patients with chronic HCV infection and 1052 individuals with spontaneous HCV clearance met inclusion criteria, in which seven studies describing rs12979860 and three studies describing rs8099917. Analysis performed in Caucasian populations indicated that rs12979860CC and rs8099917TT contributed to HCV spontaneous clearance in both dominant model (CC vs. CT+TT, P<1×10(-4); TT vs. TG+GG, P<10(-4), respectively) and co-dominant model (CC vs. CT, P<1×10(-4), CC vs. TT, P<1×10(-4); TT vs. TG, P<10(-4), TT vs. GG, P=0.012, respectively). Meta-regression analysis suggested that male proportion (P=1×10(-5)) and mean age (P=1×10(-3)) might weaken the effect of rs12979860CC, but HCV genotype 1/4 (P=4×10(-4)) might contribute to it. IL28B rs12979860CC and rs8099917TT genotypes contribute to spontaneous HCV clearance in Caucasians.

  8. Associations between CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer risk: Proof from 26 case-control studies

    PubMed Central

    He, Jing; Wang, Weiye; Xue, Wenji; Wang, Yiwei; Zheng, Leizhen; Zhu, Mei-Ling

    2016-01-01

    Cytochrome P450 1A1 (CYP1A1) enzyme is one of the most important metabolizing enzymes responsible for the metabolism of numerous xenobiotics. Numerous individual case-control studies have investigated the associations between the CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer (CRC) risk, but the conclusions were controversial. To obtain a scientific conclusion, we performed a meta-analysis based on a total of 26 publications, including 20 studies with 8665 cases and 9953 controls on rs1048943 A > G and 19 studies with 6416 cases and 7551 controls on rs4646903 T > C, respectively. The pooled analysis indicated that rs1048943 A > G was associated with an increased risk of CRC (G vs. A: OR = 1.28, 95% CI = 1.08−1.52; GG vs. AA: OR = 1.54, 95% CI = 1.25−1.91; GA vs. AA: OR = 1.26, 95% CI = 1.00−1.60; GG/GA vs. AA: OR = 1.31, 95% CI = 1.05−1.64; GG vs. GA/AA: OR = 1.56, 95% CI = 1.26−1.91). Stratification analysis showed the association between rs1048943 A > G and CRC risk was more obvious in studies with the population-based (PB) design or high quality score. The association between rs4646903 T > C and CRC risk did not reach statistical significance in the pooled analysis as well as stratification analysis. This meta-analysis demonstrated CYP1A1 rs1048943 A > G may increase the susceptibility to CRC instead of rs4646903 T > C. This conclusion suggested CYP1A1 may contribute to the pathogenesis of CRC. PMID:27384991

  9. Chandra, Extreme Ultraviolet Explorer, and Very Large Array Observations of the Active Binary System σ2 Coronae Borealis

    NASA Astrophysics Data System (ADS)

    Osten, Rachel A.; Ayres, Thomas R.; Brown, Alexander; Linsky, Jeffrey L.; Krishnamurthi, Anita

    2003-01-01

    We present the results of a coordinated observing campaign on the short-period RS CVn binary σ2 Coronae Borealis (F6V+G0V Porb=1.14 days) with the Very Large Array, the Extreme Ultraviolet Explorer, and the Chandra X-Ray Observatory High-Energy Transmission Grating Spectrometer. The radio emission is consistent with previously determined quiescent gyrosynchrotron properties. Multiple flares were seen with Extreme Ultraviolet Explorer, five occurring within two consecutive orbital periods. The first of these flares was observed with Chandra. The Chandra observations of σ2 CrB showed no systematic variations of line fluxes, widths, or Doppler shifts with orbital phase, nor any response in line width or offset due to the flare. This is consistent with both stars being equally active coronal emitters. We have developed a self-consistent method of spectral analysis to derive information from the line and continuum emissions concerning the distribution of plasma with temperature and elemental abundances. A bimodal temperature distribution is appropriate for both quiescent and flare intervals, with a stable peak at 6-8 MK and another variable enhancement at higher temperatures, with evidence for significant contribution from temperatures up to 50 MK during the flare, compared to 30 MK during quiescence. The iron abundance is subsolar during quiescence but is enriched by about a factor of 2 during a large flare seen with Chandra. The noble gas elements neon and argon show elevated abundances with respect to iron, but there is no clear evidence for any first ionization potential-based abundance pattern during quiescence or the flare. We have determined coronal electron densities from the helium-like ions O VII, Ne IX, Mg XI, and Si XIII, which imply densities >=1010 cm-3. There is a small enhancement in the electron densities derived for the flare, but it is not statistically significant. We call attention to electron temperature constraints provided by the ratios of 1s2

  10. The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women.

    PubMed

    Lurie, Galina; Gaudet, Mia M; Spurdle, Amanda B; Carney, Michael E; Wilkens, Lynne R; Yang, Hannah P; Weiss, Noel S; Webb, Penelope M; Thompson, Pamela J; Terada, Keith; Setiawan, Veronica Wendy; Rebbeck, Timothy R; Prescott, Jennifer; Orlow, Irene; O'Mara, Tracy; Olson, Sara H; Narod, Steven A; Matsuno, Rayna K; Lissowska, Jolanta; Liang, Xiaolin; Levine, Douglas A; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E; Garcia-Closas, Montserrat; Doherty, Jennifer Anne; De Vivo, Immaculata; Chen, Chu; Brinton, Louise A; Akbari, Mohammad R; Goodman, Marc T

    2011-02-08

    Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR)  = 1.17; 95% confidence interval (CI): 1.03-1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91-1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

  11. Serum lipolytic activity in Reye's syndrome.

    PubMed

    Kang, E S; Matsuo, N; Nagai, T; Greenhaw, J; Williams, P L

    1989-09-15

    High levels of the serum free fatty acids (FFA) are found in Reye's syndrome (RS). While this is attributed to enhanced adipose tissue lipolysis, the possibility that intravascular lipolysis could augment this process was investigated by measuring lipase activity in sera from RS and other subjects. Ordinarily, lipolytic activity is not detectable in serum from unheparinized subjects. Significant lipolytic activities ranging from 1-3 mumol/ml serum per hour were detected in sera from 5 of the 7 RS patients studied. Similar activities were also found in sera from two other subjects one of whom was a long-term survivor of RS and the other who had recurrent bouts of biliary obstruction and encephalopathy. Lipase activity was negligible in the serum from 2 other RS patients, 4 other long-term survivors of RS, 2 siblings, one RS parent and in 20 disease controls including patients with influenza, diabetic ketoacidosis and cerebral edema, meningitis and febrile infections with diarrhea and vomiting. None of these individuals had received heparin. An inverse relationship was found between LPL and hepatic lipase (HL) activities. Glucose levels tended to correlate directly with LPL and inversely with HL activity. The basis for the presence of LPL activity in RS sera is not known but the presence of serum lipase activity in unheparinized patients supports the notion that the TG in the circulating lipoprotein particles probably also serve as another source of FFA in the sera of RS patients.

  12. Enantioselective esterification of (R,S)-2-methylalkanoic acid with Carica papaya lipase in organic solvents.

    PubMed

    Chang, Chun-Sheng; Ho, Ssu-Ching

    2011-11-01

    Isooctane was the best reaction medium for the enantioselective esterification of (R,S)-2-methylalkanoic acid with n-butanol using Carica papaya lipase as catalyst. Increasing linear alkyl-chain length of racemic 2-methylalkanoic acids from ethyl to hexyl increased the enantioselectivity (E) from 2.1 to 98.2 for the esterification of racemic 2-methylalkanoic acids with n-butanol at 35°C. Decreasing reaction temperature from 40 to 20°C increased the enantioselectivity (E) from 14 to 33 for the esterification of racemic 2-methylhexanoic acids with n-butanol. We obtained a maximum enantioselectivity, of E = 24.3, for the enantioselective esterification of racemic 2-methylhexanoic acids with n-butanol in isooctane at water activity 0.33, and at 35°C.

  13. Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene polymorphism

    PubMed Central

    Nuolivirta, Kirsi; Törmänen, Sari; Teräsjärvi, Johanna; Vuononvirta, Juho; Koponen, Petri; Korppi, Matti; Helminen, Merja; Peltola, Ville; He, Qiushui

    2016-01-01

    Innate immunity receptors play a critical role in host defence, as well as in allergy and asthma. The aim of this exploratory study was to evaluate whether there are associations between TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and viral findings, clinical characteristics or subsequent wheezing in infants with bronchiolitis. In all, 135 full-term infants were hospitalized for bronchiolitis at age less than 6 months: 129 of them were followed-up until the age of 1.5 years. The outcome measures were repeated wheezing, use of inhaled corticosteroids, atopic dermatitis during the first 1.5 years of life and total serum immunoglobulin E (IgE). There were no significant associations between the genotypes or allele frequencies of TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and clinical characteristics or the severity of bronchiolitis during hospitalization. During follow-up, repeated wheezing was more common in children with TLR9 rs187084 variant genotype CC (30.5%) than in children with TLR9 wild-type genotype TT (12.2%) (p = 0.02, aOR 2.73, 95% CI 1.02–7.29). The TLR10 rs4129009 minor allele G was associated with elevated total serum IgE. TLR9 rs187084 gene polymorphism may be associated with post-bronchiolitis wheezing, and TLR10 rs4129009 gene polymorphism may be associated with atopy. PMID:27498757

  14. Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.

    PubMed

    Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; Nichols, Weston A; Moaddel, Ruin; Xiao, Cheng; Lester, Henry A

    2016-03-09

    Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.

  15. Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet.

    PubMed

    Sotos-Prieto, Mercedes; Guillén, Marisa; Portolés, Olga; Sorlí, José V; González, José I; Asensio, Eva M; Corella, Dolores

    2013-07-01

    The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G > A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validated questionnaire, and four groups were considered. rs6950982 (A > G) and rs1799768 (4G/5G) were only in moderate-low linkage disequilibrium (D' = 0.719; r (2) = 0.167). The most significant associations we obtained were with rs6950982 (A > G). In males, the G allele was nominally associated with higher diastolic BP (AA: 81.5 ± 10.9, AG: 82.1 ± 11.4, GG: 85.7 ± 10.5 mmHg; P additive = 0.030) and systolic BP (AA + AG: 141.4 ± 6.9 mmHg vs. GG: 149.8 ± 8.0 mmHg; P recessive = 0.036). In the whole population, the rs6950982 was also associated with plasma lipids. Subject with the G allele presented higher total cholesterol (P additive = 0.016, P recessive = 0.011), low-density lipoprotein cholesterol (P additive = 0.032, P recessive = 0.031) and triglycerides (P additive = 0.040, P recessive = 0.029). AMD modulated the effect of rs6950982 on triglyceride concentrations (P for interaction = 0.036). Greater AMD reduced the higher triglyceride concentrations in GG subjects. No significant interactions were found for the other parameters. The rs6950982 was associated with higher BP in men and higher triglycerides in the whole population, this association being modulated by AMD.

  16. XPG rs2296147 T>C polymorphism predicted clinical outcome in colorectal cancer

    PubMed Central

    Zhu, Jin-Hong; Hua, Rui-Xi; Xue, Wen-Qiong; Li, Xi-Zhao; Wang, Tong-Min; He, Jing; Jia, Wei-Hua

    2016-01-01

    Xeroderma pigmentosum group G (XPG), one of key components of nucleotide excision repair pathway (NER), is involved in excision repair of UV-induced DNA damage. Single nucleotide polymorphisms (SNPs) in the XPG gene have been reported to associate with the clinical outcome of various cancer patients. We aimed to assess the impact of four potentially functional SNPs (rs2094258 C>T, rs2296147 T>C, rs751402 G>A, and rs873601 G>A) in the XPG gene on prognosis in colorectal cancer (CRC) patients. A total of 1901 patients diagnosed with pathologically confirmed CRC were genotyped for four XPG polymorphisms. Cox proportional hazards model analysis controlled for several confounding factors was conducted to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the four included SNPs, only rs2296147 was shown to significantly affect progression-free survival (PFS) in CRC. Patients carrying rs2296147 CT/TT genotype had a significantly shorter median 10 years PFS than those carrying CC genotype (88.5 months vs. 118.1 months), and an increased progression risk were observed with rs2296147 (HR = 1.324, 95% CI = 1.046–1.667). Moreover, none of the four SNPs were associated with overall survival. In conclusion, our study showed that XPG rs2296147 CT/TT variants conferred significant survival disadvantage in CRC patients in term of PFS. XPG rs2296147 polymorphism could be predictive of unfavorable prognosis of CRC patients. PMID:26887052

  17. rs3806268 of NLRP3 gene polymorphism is associated with the development of primary gout

    PubMed Central

    Deng, Jianping; Lin, Wen; Chen, Yunpeng; Wang, Xin; Yin, Zhong; Yao, Chunhong; Liu, Tangbing; Lv, Yonghong

    2015-01-01

    The aim of the present study was to investigate the association between seven functional SNPs in NALP3 gene and the susceptibility to primary gout. A total of 247 patients with primary gout and 247 controls were selected in this study. Genotyping of NALP3 rs4612666, rs3806268, rs12239046, rs10754558, rs7512998, rs12137901 and rs12565738 was performed using the Sequenom MassARRAY platform. Comparison analysis showed that primary gout patients were more likely to have a higher body mass index, DBP, SBP, TG, urea nitrogen and uric acid (P < 0.05). According to logistic regression analysis, individuals carrying with the GG genotype of rs3806268 were associated with increased risk of primary gout when compared with the AA genotype (OR=1.83, 95% CI=1.03-3.26). However, no significant associations were identified for the remaining SNPs. In conclusion, we found a significant association between rs3806268 in NLRP3 gene and the risk of primary gout in a Chinese population. Further clinical and genetic studies are required to investigate the mechanisms underlying the association between NALP3 polymorphisms and the development of primary gout. PMID:26722603

  18. rs3806268 of NLRP3 gene polymorphism is associated with the development of primary gout.

    PubMed

    Deng, Jianping; Lin, Wen; Chen, Yunpeng; Wang, Xin; Yin, Zhong; Yao, Chunhong; Liu, Tangbing; Lv, Yonghong

    2015-01-01

    The aim of the present study was to investigate the association between seven functional SNPs in NALP3 gene and the susceptibility to primary gout. A total of 247 patients with primary gout and 247 controls were selected in this study. Genotyping of NALP3 rs4612666, rs3806268, rs12239046, rs10754558, rs7512998, rs12137901 and rs12565738 was performed using the Sequenom MassARRAY platform. Comparison analysis showed that primary gout patients were more likely to have a higher body mass index, DBP, SBP, TG, urea nitrogen and uric acid (P < 0.05). According to logistic regression analysis, individuals carrying with the GG genotype of rs3806268 were associated with increased risk of primary gout when compared with the AA genotype (OR=1.83, 95% CI=1.03-3.26). However, no significant associations were identified for the remaining SNPs. In conclusion, we found a significant association between rs3806268 in NLRP3 gene and the risk of primary gout in a Chinese population. Further clinical and genetic studies are required to investigate the mechanisms underlying the association between NALP3 polymorphisms and the development of primary gout.

  19. Spatial distribution of carbon dioxide absorption and emission in Chungcheongbuk-do, South Korea using RS and GIS method

    NASA Astrophysics Data System (ADS)

    Park, Jin-Ki; Na, Sang-il; Park, Jong-Hwa

    2011-11-01

    Climate change has been an important issue particularly in recent years. Climate change has been reported as a phenomena caused by human activities as identified in the IPCC Fourth Assessment Report (AR4) in 2007, and in order to prevent negative impacts to our planet, conscious efforts to reduce greenhouse gases are necessary worldwide. In addition, Korea's interest in global climate change is growing. In reality, symptoms of global warming on the Korean Peninsula are visible in the air, on the land and in changes patterns to the normal levels and contents of Korea's oceans. Impacts of global warming result in abnormal temperature fluctuation, typhoons, regional flooding and desertification with such extreme and that are arguably more frequent occurrences of natural disasters quickly becoming a general problem for the community as a whole. On the other hand, the development of IT technology and the improvement and use of satellite technology have ensured better access to RS technique and utilization. Due to RS technology is ability to monitor it has become widely used in farming applications, environment prediction and planning and ecology studies and analysis. The purpose of this study is to assess emission and absorption in relation to geographical features and to be better able to deliver environment information to produce a spatial map of carbon dioxide in Chungbuk by using RS and GIS with a focus on carbon dioxide emission and its direct absorption caused by tree growth according to energy consumption.

  20. Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA Synthetase (hGlyRS) during Catalysis*

    PubMed Central

    Deng, Xiangyu; Qin, Xiangjing; Chen, Lei; Jia, Qian; Zhang, Yonghui; Zhang, Zhiyong; Lei, Dongsheng; Ren, Gang; Zhou, Zhihong; Wang, Zhong; Li, Qing; Xie, Wei

    2016-01-01

    Glycyl-tRNA synthetase (GlyRS) is the enzyme that covalently links glycine to cognate tRNA for translation. It is of great research interest because of its nonconserved quaternary structures, unique species-specific aminoacylation properties, and noncanonical functions in neurological diseases, but none of these is fully understood. We report two crystal structures of human GlyRS variants, in the free form and in complex with tRNAGly respectively, and reveal new aspects of the glycylation mechanism. We discover that insertion 3 differs considerably in conformation in catalysis and that it acts like a “switch” and fully opens to allow tRNA to bind in a cross-subunit fashion. The flexibility of the protein is supported by molecular dynamics simulation, as well as enzymatic activity assays. The biophysical and biochemical studies suggest that human GlyRS may utilize its flexibility for both the traditional function (regulate tRNA binding) and alternative functions (roles in diseases). PMID:26797133

  1. Vibrio parahaemolyticus has a homolog of the Vibrio cholerae toxRS operon that mediates environmentally induced regulation of the thermostable direct hemolysin gene.

    PubMed Central

    Lin, Z; Kumagai, K; Baba, K; Mekalanos, J J; Nishibuchi, M

    1993-01-01

    In an effort to identify the regulatory gene controlling the expression of the tdh gene, encoding the thermostable direct hemolysin of Vibrio parahaemolyticus, we examined total DNA of AQ3815 (a Kanagawa phenomenon-positive strain) for sequences homologous to that of the toxR gene of Vibrio cholerae. The extracted DNA gave a weak hybridization signal under reduced-stringency conditions with a toxR-specific DNA probe. Cloning and sequence analysis of the probe-positive sequence revealed an operon (Vp-toxRS) which was highly similar to the toxRS operon of V. cholerae (Vc-toxRS) (52 and 62% similarities in the two genes, respectively). The deduced amino acid sequences of the Vp-toxRS gene products (Vp-ToxRS) contained regions similar to the proposed transmembrane and activity domains of the Vc-toxRS gene products (Vc-ToxRS). All clinical and environmental strains of V. parahaemolyticus examined possessed the Vp-toxRS genes. In the presence of Vp-ToxS, Vp-ToxR promoted expression of the tdh2 gene, one of two tdh genes (tdh1 and tdh2) carried by Kanagawa phenomenon-positive strains. The DNA sequence located 144 bp upstream of the tdh2 coding region was shown to be important for the Vp-ToxR-stimulated expression of the tdh2 gene in an Escherichia coli background. Comparative analysis of AQ3815 and its isogenic Vp-toxR null mutant gave the following results: (i) Vp-ToxR promoted, in an AQ3815 background, expression of the tdh gene to different degrees in various culture media, with KP broth (2% peptone, 0.5% NaCl, 0.03 M KH2PO4, pH 6.2) being most effective (12-fold); (ii) the promotion of tdh gene expression in KP broth was at the level of transcription; and (iii) Vp-ToxR was essential for demonstration of enterotoxic activity of AQ3815 in the rabbit ileal loop, a model previously used to demonstrate thermostable direct hemolysin-mediated enterotoxic activity of AQ3815. These results demonstrate that Vp-ToxR and Vc-ToxR share a strikingly similar function, i.e., direct

  2. Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia.

    PubMed

    Vargas-Torres, Sandra Liliana; Portari, Elyzabeth Avvad; Silva, Amanda Lima; Klumb, Evandro Mendes; da Rocha Guillobel, Heloísa Carneiro; de Camargo, Maria José; Santos-Rebouças, Cíntia Barros; Russomano, Fábio Bastos; Macedo, Jacyara Maria Brito

    2016-08-01

    The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions.

  3. Protective role of +294 T/C (rs2016520) polymorphism of PPARD in Mexican patients with colorectal cancer.

    PubMed

    Rosales-Reynoso, M A; Wence-Chavez, L I; Arredondo-Valdez, A R; Dumois-Petersen, S; Barros-Núñez, P; Gallegos-Arreola, M P; Flores-Martínez, S E; Sánchez-Corona, J

    2017-01-23

    PPARD encodes for peroxisome proliferator-activated receptor delta, which plays a significant role in controlling lipid metabolism, atherosclerosis, inflammation, cancer growth, progression, and apoptosis. Accumulated evidence suggests that the polymorphism rs2016520 in PPARD is associated with lipid metabolism, obesity, metabolic syndrome, and type 2 diabetes mellitus. The aim of this study was to determine whether the single nucleotide polymorphism +294T/C (rs2016520) in PPARD is associated with colorectal cancer (CRC) in the Mexican population. Genomic DNA from 178 CRC patients and 97 healthy blood donors was analyzed. The polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Results demonstrated that patients with the T/C genotype for the +294T/C (rs2016520) polymorphism present a protective role against CRC [odds ratio (OR) = 0.39; 95% confidence interval (CI) = 0.22-0.69; P = 0.0008]. This association was also evident for the T/C genotype in the stratified analysis by tumor-node-metastasis stages I+II (OR = 0.26, P = 0.0332) and III+IV (OR = 0.44, P = 0.0067). However, in the stratified analysis by tumor location, we observed an increased risk of rectal cancer (OR = 7.57, P = 0.0403) vs colon cancer (OR = 4.87, P = 0.234) in patients carrying the C/C genotype and under the dominant and recessive models of inheritance. In conclusion, for the first time, the association between the +294T/C (rs2016520) polymorphism and colorectal cancer has been studied in Mexican patients. Our results reveal that variations in PPARD may play a significant role in genetic susceptibility to colorectal cancer.

  4. The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070

    PubMed Central

    Shi, Meng; Xia, Jianhong; Xing, Huaixin; Yang, Wenjun; Xiong, Xiangyu; Pan, Wenting; Han, Sichong; Shang, Jinhua; Zhou, Changchun; Zhou, Liqing; Yang, Ming

    2016-01-01

    Metallopeptidase 13 (MMP13), a well-known and highly regulated zinc-dependent MMP collagenase, plays a crucial part in development and progression of esophageal squamous cell carcinoma (ESCC). Therefore, we examined associations between ESCC susceptibility and four haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression model. After analyzing 1588 ESCC patients and frequency-matched 1600 unaffected controls, we found that MMP13 rs2252070 G > A genetic polymorphism is significantly associated with ESCC risk in Chinese Han populations (GA: OR = 0.63, 95% CI = 0.54–0.74, P = 1.7 × 10−6, AA: OR = 0.73, 95% CI = 0.66–0.81, P = 1.8 × 10−6). Interestingly, the rs2252070 G-to-A change was shown to diminish a Sp1-binding site in ESCC cells. Reporter gene assays indicated that the rs2252070 A allele locating in a potential MMP13 promoter has low promoter activities. After measuring MMP13 gene expression in sixty-six pairs of esophageal cancer and normal tissues, we observed that the rs2252070 A protective allele carriers showed decreased oncogene MMP13 expression. Results of these analyses underline the support of the notion that MMP13 might function as a key oncogene in esophageal carcinogenesis. PMID:27245877

  5. The Sp1-mediaded allelic regulation of MMP13 expression by an ESCC susceptibility SNP rs2252070.

    PubMed

    Shi, Meng; Xia, Jianhong; Xing, Huaixin; Yang, Wenjun; Xiong, Xiangyu; Pan, Wenting; Han, Sichong; Shang, Jinhua; Zhou, Changchun; Zhou, Liqing; Yang, Ming

    2016-06-01

    Metallopeptidase 13 (MMP13), a well-known and highly regulated zinc-dependent MMP collagenase, plays a crucial part in development and progression of esophageal squamous cell carcinoma (ESCC). Therefore, we examined associations between ESCC susceptibility and four haplotype-tagging single nucleotide polymorphisms (htSNPs) using a two stage case-control strategy. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression model. After analyzing 1588 ESCC patients and frequency-matched 1600 unaffected controls, we found that MMP13 rs2252070 G > A genetic polymorphism is significantly associated with ESCC risk in Chinese Han populations (GA: OR = 0.63, 95% CI = 0.54-0.74, P = 1.7 × 10(-6), AA: OR = 0.73, 95% CI = 0.66-0.81, P = 1.8 × 10(-6)). Interestingly, the rs2252070 G-to-A change was shown to diminish a Sp1-binding site in ESCC cells. Reporter gene assays indicated that the rs2252070 A allele locating in a potential MMP13 promoter has low promoter activities. After measuring MMP13 gene expression in sixty-six pairs of esophageal cancer and normal tissues, we observed that the rs2252070 A protective allele carriers showed decreased oncogene MMP13 expression. Results of these analyses underline the support of the notion that MMP13 might function as a key oncogene in esophageal carcinogenesis.

  6. The rs4646 and rs12592697 Polymorphisms in CYP19A1 Are Associated with Disease Progression among Patients with Breast Cancer from Different Racial/Ethnic Backgrounds

    PubMed Central

    Armamento-Villareal, Reina; Shah, Vallabh O.; Aguirre, Lina E.; Meisner, Angela L. W.; Qualls, Clifford; Royce, Melanie E.

    2016-01-01

    Given the racial/ethnic disparities in breast cancer, we evaluated the association between CYP19A1 single nucleotide polymorphisms (SNPs) on disease progression in women with breast cancer from different racial/ethnic backgrounds. This is a cross-sectional analysis of data from 327 women with breast cancer in the Expanded Breast Cancer Registry program of the University of New Mexico. Stored DNA samples were analyzed for CYP19A1 SNPs using a custom designed microarray panel. Genotype-phenotype correlations were analyzed. Of the 384 SNPs, 2 were associated with clinically significant outcomes, the rs4646 and rs12592697. The T allele for the rs4646 was associated with advanced stage of the disease at the time of presentation (odds ratio [OR]:1.8, confidence intervals [CI]: 1.05–3.13, p < 0.05) and a more progressive disease (OR: 2.1 [CI: 1.1–4.0], p = 0.04). For the rs12592697, the variant T allele was more frequent in Hispanic women and associated with a more progressive disease (OR: 2.05 [CI: 1.0–4.0], p = 0.04). However, further analysis according to menopausal status showed that the association between these 2 SNPs with disease progression or the stage at diagnosis are confined only to postmenopausal women. The odds ratios of disease progression among postmenopausal women carrying the T allele for the rs4646 and rs12592697 are 3.05 (1.21, 7.74, p = 0.02) and 3.80 (1.24, 11.6, p = 0.02), respectively. Regardless, differences in disease progression among the different genotypes for both SNPs disappeared after adjustment for treatment. In summary, the rs4646 and the rs12592697 SNPs in CYP19A1 are associated with differences in disease progression in postmenopausal women. However, treatment appears to mitigate the differences in genetic risk. PMID:27994616

  7. Muscle-Related Polymorphisms (MSTN rs1805086 and ACTN3 rs1815739) Are Not Associated with Exceptional Longevity in Japanese Centenarians

    PubMed Central

    Yvert, Thomas; Zempo, Hirofumi; Naito, Hisashi; Abe, Yukiko; Arai, Yasumichi; Murakami, Haruka; Miyachi, Motohiko; Pareja-Galeano, Helios; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro

    2016-01-01

    Myostatin (MSTN) and α-actinin-3 (ACTN3) genes are potentially associated with preservation of muscle mass and oxidative capacity, respectively. To explore the possible role of these genes in exceptional longevity (EL), the allele/genotype frequency distribution of two polymorphisms in MSTN (rs1805086, K153R) and ACTN3 (rs1815739, R577X) was studied in Japanese centenarians of both sexes (n = 742) and healthy controls (n = 814). The rs1805086 R-allele (theoretically associated with muscle mass preservation at the expense of oxidative capacity) was virtually absent in the two groups, where genotype distributions were virtually identical. Likewise, no differences in allele (p = 0.838 (women); p = 0.193 (men); p = 0.587 (both sexes)) or genotype distribution were found between groups for ACTN3 rs1815739 (p = 0.975 (women), p = 0.136 (men), p = 0.752 (both sexes)). Of note, however, the frequency of the rs1805086 R-allele observed here is the lowest been reported to date whereas that of the ‘highly oxidative/efficient’ rs1815739 XX genotype in Japanese male centenarians (33.3%) or supercentenarians of both sexes (≥110 years) are the highest (32.6%), for a non-American population. No definite conclusions can be inferred in relation to EL owing to its lack of association with both rs1815739 and rs1805086. However, it cannot be excluded that these gene variants could eventually be related to a “healthy” metabolic phenotype in the Japanese population. Further research might determine if such metabolic profile is among the factors that can potentially predispose these individuals to live longer than Caucasians and what genetic variants might be actually involved. PMID:27861536

  8. Association between Insulin-Like Growth Factor 1 Gene rs12423791 or rs6214 Polymorphisms and High Myopia: A Meta-Analysis

    PubMed Central

    Guo, Lan; Du, Xueying; Lu, Ciyong; Zhang, Wei-Hong

    2015-01-01

    Objective To evaluate the association of insulin-like growth factor 1 gene rs12423791 and rs6214 polymorphisms with high myopia. Methods An electronic search was conducted on PubMed, Embase, the Cochrane Library and the Chinese Biological Abstract Database for articles published prior to May 6, 2014. A meta-analysis was performed using Revman 5.1 and Stata 12.0, and the odds ratios with 95% confidence intervals were calculated in fixed or random effects models based on the results of the Q test. The subgroup analysis was conducted on the basis of the various regions, the sensitivity analysis was also performed to evaluate the stability of the results, and the publication bias was evaluated by a funnel plot and Egger’s linear regression analysis. Results This comprehensive meta-analysis included 2808 high myopia patients and 2778 controls from five unrelated studies. The results demonstrated that the significant association was not present in any genetic models between IGF-1 rs12423791 or rs6214 and high myopia. However, subgroup analysis indicated that rs12423791 polymorphism was associated with high myopia in the Chinese populations in the allelic contrast model (C vs. G: OR=1.24, 95% CI=1.04-1.48 in the fixed-effects model), the dominant model (CC+CG vs. GG: OR=1.40, 95% CI=1.16-1.69 in the fixed-effects model), and the codominant model (CG vs. GG: OR=1.37, 95% CI= 1.12-1.68 in the fixed-effects model). Additionally, none of the individual studies significantly affected the association between IGF-1 rs12423791 and high myopia, according to sensitivity analysis. Conclusion This meta-analysis shows that IGF-1 rs12423791 or rs6214 gene polymorphism is not associated with high myopia. PMID:26076017

  9. Polymorphisms in TRPV1 and TAS2Rs associate with sensations from sampled ethanol

    PubMed Central

    Allen, Alissa L.; McGeary, John E.; Hayes, John E.

    2014-01-01

    Background Genetic variation in chemosensory genes can explain variability in individual’s perception of and preference for many foods and beverages. To gain insight into variable preference and intake of alcoholic beverages, we explored individual variability in the responses to sampled ethanol. In humans, ethanol elicits sweet, bitter and burning sensations. Here, we explore the relationship between variation in ethanol sensations and polymorphisms in genes encoding bitter taste receptors (TAS2Rs) and a polymodal nociceptor (TRPV1). Methods Caucasian participants (n=93) were genotyped for 16 SNPs in TRPV1, 3 SNPs in TAS2R38 and 1 SNP in TAS2R13. Participants rated sampled ethanol on a generalized Labeled Magnitude Scale. Two stimuli were presented: a 16% ethanol whole mouth sip-and-spit solution with a single time-point rating of overall intensity, and a cotton swab saturated with 50% ethanol on the circumvallate papillae (CV) with repeated ratings made over 3 minutes. Area under the curve (AUC) was calculated for the time-intensity data. Results The ethanol whole mouth solution had overall intensity ratings near ‘very strong’. Burning/stinging had the highest mean AUC values, followed by bitterness and sweetness. Whole mouth intensity ratings were significantly associated with burning/stinging and bitterness AUC values on the CV. Three TRPV1 SNPs (rs224547, rs4780521, rs161364) were associated with ethanol sensations on the CV, with two (rs224547 and rs4780521) exhibiting strong linkage disequilibrium. Additionally, the TAS2R38 SNPs rs713598, rs1726866, and rs10246939 formed a haplotype, and were associated with bitterness on the CV. Lastly, overall intensity for whole mouth ethanol associated with the TAS2R13 SNP rs1015443. Conclusions These data suggest genetic variations in TRPV1 and TAS2Rs influence sensations from sampled ethanol and may potentially influence how individuals initially respond to alcoholic beverages. PMID:25257701

  10. Charpy impact test results of four low activation ferritic alloys irradiated at 370{degrees}C to 15 DPA

    SciTech Connect

    Schubert, L.E.; Hamilton, M.L.; Gelles, D.S.

    1996-10-01

    Miniature CVN specimens of four low activation ferritic alloys have been impact tested following irradiation at 370{degrees}C to 15 dpa. Comparison of the results with those of control specimens indicates that degradation in the impact behavior occurs in each of these four alloys. The 9Cr-2W alloy referred to as GA3X and the similar alloy F82H with 7.8Cr-2W appear most promising for further consideration as candidate structural materials in fusion energy system applications. These two alloys exhibit a small DBTT shift to higher temperatures but show increased absorbed energy on the upper shelf.

  11. Association of the ACE rs4646994 and rs4341 polymorphisms with the progression of carotid atherosclerosis in slovenian patients with type 2 diabetes mellitus

    PubMed Central

    Merlo, S; Novák, J; Tkáčová, N; Nikolajević Starčević, J; Šantl Letonja, M; Makuc, J; Cokan Vujkovac, A; Letonja, J; Bregar, D; Zorc, M; Rojko, M; Mankoč, S; Kruzliak, P

    2015-01-01

    Abstract The current study was designed to reveal possible associations between the angiotensin-converting-enzyme (ACE) gene polymorphisms (rs4646994 and rs4341) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM) in a 4-year-long follow-up study. Five hundred and ninety-five T2DM subjects and 200 control subjects were enrolled. Genotyping of ACE polymorphisms was performed using KASPar assays, and ultrasound examinations were performed twice (at the enrollment and at follow-up). With regard to the progression of atherosclerosis in subjects with T2DM, statistically significant differences were demonstrated in the change of the sum of carotid plaques thickness for the rs4646994 polymorphism. We did not demonstrate an association between the tested polymorphisms (rs4646994 and rs4341) and either carotid intima media thickness (CIMT) or CIMT progression in a 3.8-year period. In our study, we demonstrated that subjects with T2DM with the DD genotype of the rs4646994 [ACE insertion/deletion (I/D)] polymorphism had faster progression of atherosclerosis in comparison to subjects with other genotypes. PMID:27785395

  12. Association between 8q24 (rs13281615 and rs6983267) polymorphism and breast cancer susceptibility: a meta-analysis involving 117,355 subjects.

    PubMed

    Zhang, Yafei; Zeng, Xianling; Lu, Hongwei; Ji, Hong; Zhao, Enfa; Li, Yiming

    2016-10-18

    Published data on the association between 8q24 polymorphism and breast cancer (BC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between 8q24 (rs13281615 and rs6983267) polymorphism and BC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to August 13, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Twenty-six studies published from 2008 to 2014, with a total of 52,683 cases and 64,672 controls, were included in this meta-analysis. The pooled results showed that there was significant association between 8q24 rs13281615 polymorphism and BC risk in any genetic model. In the subgroup analysis by ethnicity, the effects remained in Asians and Caucasians. However, no genetic models reached statistical association in Africans. There was no association in any genetic model in rs6983267. This meta-analysis suggests that 8q24 rs13281615 polymorphism is a risk factor for susceptibility to BC in Asians, Caucasians and in overall population, While, there was no association in Africans. The rs6983267 polymorphism has no association with BC risk in any genetic model. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

  13. The Minor Allele of rs7574865 in the STAT4 Gene Is Associated with Increased mRNA and Protein Expression

    PubMed Central

    Lamana, Amalia; López-Santalla, Mercedes; Castillo-González, Raquel; Ortiz, Ana María; Martín, Javier; García-Vicuña, Rosario; González-Álvaro, Isidoro

    2015-01-01

    Objective The T allele of rs7574865 in STAT4 confers risk of developing autoimmune disorders. However, its functional significance remains unclear. Here we analyze how rs7574865 affects the transcription of STAT4 and its protein expression. Methods We studied 201 patients (80% female; median age, 54 years; median disease duration, 5.4 months) from PEARL study. Demographic, clinical, laboratory and therapeutic data were collected at each visit. IL-6 serum levels were measured by enzyme immune assay. The rs7574865 was genotyped using TaqMan probes. The expression levels of STAT4 mRNA were determined at 182 visits from 69 patients using quantitative real-time polymerase chain reaction. STAT4 protein was assessed by western blot in 62 samples from 34 patients. To determine the effect of different variables on the expression of STAT4 mRNA and protein, we performed multivariate longitudinal analyses using generalized linear models. Results After adjustment for age, disease activity and glucocorticoid dose as confounders, the presence of at least one copy of the T allele of rs7574865 was significantly associated with higher levels of STAT4 mRNA. Similarly, TT patients showed significantly higher levels of STAT4 protein than GG patients. IL-6 induced STAT4 and STAT5 phosphorylation in peripheral blood lymphocytes. Patients carrying at least one T allele of rs7574865 displayed lower levels of serum IL-6 compared to GG homozygous; by contrast the production of C-reactive protein was similar in both populations. Conclusion Our data suggest that the presence of the rs7574865 T allele enhances STAT4 mRNA transcription and protein expression. It may enhance the signaling of molecules depending on the STAT4 pathway. PMID:26569609

  14. High therapeutic potential of positive allosteric modulation of α7 nAChRs in a rat model of traumatic brain injury: Proof-of-concept

    PubMed Central

    Gatson, Joshua W.; Simpkins, James W.; Uteshev, Victor V.

    2015-01-01

    There are currently no clinically-efficacious drug therapies to treat brain damage secondary to traumatic brain injury (TBI). In this proof-of-concept study, we used a controlled cortical impact model of TBI in young adult rats to explore a novel promising approach that utilizes PNU-120596, a previously-reported highly selective Type-II positive allosteric modulator (α7-PAM) of α7 nicotinic acetylcholine receptors (nAChRs). α7-PAMs enhance and prolong α7 nAChR activation, but do not activate α7 nAChRs when administered without an agonist. The rational basis for the use of an α7-PAM as a post-TBI treatment is tripartite and arises from: 1) the intrinsic ability of brain injury to elevate extracellular levels of choline (a ubiquitous cell membrane-building material and a selective endogenous agonist of α7 nAChRs) due to the breakdown of cell membranes near the site and time of injury; 2) the ubiquitous expression of functional α7 nAChRs in neuronal and glial/immune brain cells; and 3) the potent neuroprotective and anti-inflammatory effects of α7 nAChR activation. Therefore, both neuroprotective and anti-inflammatory effects can be achieved post-TBI by targeting only a single player (i.e., the α7 nAChR) using α7-PAMs to enhance the activation of α7 nAChRs by injury-elevated extracellular choline. Our data support this hypothesis and demonstrate that subcutaneous administration of PNU-120596 post-TBI in young adult rats significantly reduces both brain cell damage and reactive gliosis. Therefore, our results introduce post-TBI systemic administration of α7-PAMs as a promising therapeutic intervention that could significantly restrict brain injury post-TBI and facilitate recovery of TBI patients. PMID:25647232

  15. Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus

    PubMed Central

    Sakiyama, Masayuki; Matsuo, Hirotaka; Nakaoka, Hirofumi; Yamamoto, Ken; Nakayama, Akiyoshi; Nakamura, Takahiro; Kawai, Sayo; Okada, Rieko; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-01-01

    Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 × 10−18, odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that “A” allele (Lys) of rs671 plays a protective role in the development of gout. PMID:27181629

  16. Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility.

    PubMed

    Chen, Guangyuan; Fu, Xiuhua; Wang, Guangyu; Liu, Guiyou; Bai, Xiuping

    2015-05-21

    Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10-22, odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22-1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10-53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples.

  17. CLU rs9331888 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Caucasian But Not East Asian Populations.

    PubMed

    Zhang, Shuyan; Li, Xuling; Ma, Guoda; Jiang, Yongshuai; Liao, Mingzhi; Feng, Rennan; Zhang, Liangcai; Liu, Jiafeng; Wang, Guangyu; Zhao, Bin; Jiang, Qinghua; Li, Keshen; Liu, Guiyou

    2016-04-01

    Large-scale genome-wide association studies (GWAS) identified three single nucleotide polymorphisms rs11136000, rs2279590, and rs9331888 in CLU gene to be significantly associated with Alzheimer's disease (AD) in Caucasian ancestry. Both rs11136000 and rs2279590 variants were successfully replicated in Asian population. However, previous studies reported either a weak association or no association between rs9331888 polymorphism and AD in Asian population. Here, we searched the PubMed, AlzGene, and Google Scholar databases. We selected 12 independent studies that evaluated the association between the rs9331888 polymorphism and AD using a case-control design. Using an additive model, we did not identify significant heterogeneity among these 12 studies. We observed significant association between rs9331888 polymorphism and AD in pooled populations (P = 2.26E - 07, odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.06-1.14). In subgroup analysis, we did not identify significant heterogeneity in both Asian and Caucasian populations. We identified significant association in Caucasian population (P = 1.67E - 08, OR = 1.13, 95% CI 1.08-1.18) but not in East Asian population (P = 0.49, OR = 1.02, 95% CI 0.96-1.10).

  18. Validation of the Official Slovak Version of the Unified Dyskinesia Rating Scale (UDysRS).

    PubMed

    Skorvanek, Matej; Minar, Michal; Grofik, Milan; Kracunova, Katarina; Han, Vladimir; Cibulcik, Frantisek; Necpal, Jan; Gurcik, Ladislav; Valkovic, Peter

    2015-01-01

    After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinson's disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be ≥0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was ≥0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society.

  19. Association between BDNF-rs6265 and obesity in the Boston Puerto Rican Health Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study is to examine a functional variant (rs6265) in the BDNF gene interacting with dietary intake modulate obesity traits in the Boston Puerto Rican Health Study population. BDNF rs6265 was genotyped in 1147 Puerto Ricans (aged 45-75 years), and examined for association with o...

  20. Nanostructured lipid carrier surface modified with Eudragit RS 100 and its potential ophthalmic functions

    PubMed Central

    Zhang, Wenji; Li, Xuedong; Ye, Tiantian; Chen, Fen; Yu, Shihui; Chen, Jianting; Yang, Xinggang; Yang, Na; Zhang, Jinsong; Liu, Jinlu; Pan, Weisan; Kong, Jun

    2014-01-01

    This study was carried out to evaluate the ocular performance of a cationic Eudragit (EDU) RS 100-coated nanostructured lipid carrier (NLC). The genistein encapsulated NLC (GEN-NLC) was produced using the melt-emulsification technique followed by surface absorption of EDU RS 100. The EDU RS 100 increased the surface zeta potential from −7.46 mV to +13.60 mV, by uniformly forming a spherical coating outside the NLC surface, as shown by transmission electron microscopy images. The EDU RS 100 on the NLC surface effectively improved the NLC stability by inhibiting particle size growth. The obtained EDU RS 100-GEN-NLC showed extended precorneal clearance and a 1.22-fold increase in AUC (area under the curve) compared with the bare NLC in a Gamma scintigraphic evaluation. The EDU RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients (Papp) compared with references. Draize and cytotoxicity testing confirmed that the developed EDU RS 100-GEN-NLC was nonirritant to ocular tissues and nontoxic to corneal cells. These results indicate that the NLC surface modified by EDU RS 100 significantly improves the NLC properties and exhibits many advantages for ocular use. PMID:25246787

  1. Brush Seal Arrangement for the RS-68 Turbopump Set

    NASA Technical Reports Server (NTRS)

    Nunez, D.; Ransom, D.; Prueger, G.

    2006-01-01

    The nature of the RS-68 turbopumps requires that the hydrogen seals separating the pump from the turbine must have extremely low levels of leakage and be contained in small packages. Conventional seal technologies are not able to reasonably satisfy such design requirements. A review of experimental measurements and analysis publications suggests that brush seals are well suited for the design requirements. Brush seals are shown to have less leakage than conventional labyrinth and damper seals and have no adverse effects on the rotordynamics of the machine. The bulk-flow analysis presented by Hendricks et al. is used as a guideline to create a spreadsheet that provides mass flow through the seal and heat generated by the rubbing contact of the bristles on the shaft. The analysis is anchored to published data for LN2 and LH2 leakage tests. Finally, the analysis is used to design seals for both applications. It is observed that the most important analysis parameter is the thickness of the bristle pack and its relationship to seal clearance, lay angle and pressure drop.

  2. The axisymmetric envelopes of RS Cnc and EP Aqr

    NASA Astrophysics Data System (ADS)

    Le Bertre, T.; Hoai, D. T.; Nhung, P. T.; Winters, J. M.

    2016-12-01

    We report on observations obtained at IRAM on two semi-regular variable Asymptotic Giant Branch (AGB) stars, RS Cnc and EP Aqr, undergoing mass loss at an intermediate rate of ˜ 10^{-7} MȯMd. Interferometric data obtained with the Plateau-de-Bure interferometer (NOEMA) have been combined with On-The-Fly maps obtained with the 30-m telescope in the CO(1-0) and (2-1) rotational lines. The spectral maps of spatially resolved sources reveal an axisymmetric morphology in which matter is flowing out at a low velocity (˜ 2 kms) in the equatorial planes, and at a larger velocity (˜ 8 kms) along the polar axes. There are indications that this kind of morpho-kinematics is relatively frequent among stars at the beginning of their evolution on the Thermally-Pulsing AGB, in particular among those that show composite CO line profiles, and that it might be caused by the presence of a companion. We discuss the progress that could be expected for our understanding of the mass loss mechanisms in this kind of sources by increasing the spatial resolution of the observations with ALMA or NOEMA.

  3. An investment in the Three Rs can be very profitable.

    PubMed

    Curren, Rodger

    2009-12-01

    The Principles of Humane Experimental Technique by William Russell and Rex Burch provides exceptional value, both to practitioners of alternative methodologies and to bibliophiles who enjoy the pursuit of an out-of-print book. I was stimulated to find an original edition by my first visits to FRAME and its Chairman, Michael Balls. The search continued for several years, until I was able to find an edition suitable for presentation to him. During this hunt, I was able to learn a great deal about the Three Rs of Replacement, Reduction and Refinement, and the programmes that FRAME initiated to educate scientists and the general public about alternative approaches. Very importantly, I was able to use many of FRAME's successful strategies to build up a similar organisation in the United States, the Institute for In Vitro Sciences. The double value of this book is now revealed - not only are its concepts scientifically and ethically valuable, but the price now being charged by secondhand booksellers means a more than ten-fold increase in the value of my investment!

  4. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders

    PubMed Central

    Franklin, Kelle M.; Asatryan, Liana; Jakowec, Michael W.; Trudell, James R.; Bell, Richard L.; Davies, Daryl L.

    2014-01-01

    Alcohol use disorders (AUDs) have a staggering socioeconomic impact. Few therapeutic options are available, and they are largely inadequate. These shortcomings highlight the urgent need to develop effective medications to prevent and/or treat AUDs. A critical barrier is the lack of information regarding the molecular target(s) by which ethanol (EtOH) exerts its pharmacological activity. This review highlights findings implicating P2X4 receptors (P2X4Rs) as a target for the development of therapeutics to treat AUDs and discusses the use of ivermectin (IVM) as a potential clinical tool for treatment of AUDs. P2XRs are a family of ligand-gated ion channels (LGICs) activated by extracellular ATP. Of the P2XR subtypes, P2X4Rs are expressed the most abundantly in the CNS. Converging evidence suggests that P2X4Rs are involved in the development and progression of AUDs. First, in vitro studies report that pharmacologically relevant EtOH concentrations can negatively modulate ATP-activated currents. Second, P2X4Rs in the mesocorticolimbic dopamine system are thought to play a role in synaptic plasticity and are located ideally to modulate brain reward systems. Third, alcohol-preferring (P) rats have lower functional expression of the p2rx4 gene than alcohol-non-preferring (NP) rats suggesting an inverse relationship between alcohol intake and P2X4R expression. Similarly, whole brain p2rx4 expression has been shown to relate inversely to innate 24 h alcohol preference across 28 strains of rats. Fourth, mice lacking the p2rx4 gene drink more EtOH than wildtype controls. Fifth, IVM, a positive modulator of P2X4Rs, antagonizes EtOH-mediated inhibition of P2X4Rs in vitro and reduces EtOH intake and preference in vivo. These findings suggest that P2X4Rs contribute to EtOH intake. The present review summarizes recent findings focusing on the P2X4R as a molecular target of EtOH action, its role in EtOH drinking behavior and modulation of its activity by IVM as a potential therapy

  5. Acquisition, Retention, and Recall of Memory After Injection of RS67333, a 5-HT4 Receptor Agonist, Into the Nucleus Basalis Magnocellularis of the Rat

    PubMed Central

    Orsetti, Marco; Dellarole, Anna; Ferri, Simona; Ghi, Piera

    2003-01-01

    The serotonin 5-HT4 subtype receptor is predominantly localized into anatomical structures linked to memory and cognition. A few experimental studies report that the acute systemic administration of selective 5-HT4 agonists has ameliorative effects on memory performance, and that these effects are reversed by contemporary administration of 5-HT4 receptor antagonists. To verify whether this procognitive action occurs via the activation of the cholinergic nucleus basalis magnocellularis (NBM)-cortical pathways, we examined the effects of RS67333, a selective partial agonist of the 5-HT4 receptor, on rat performance in a place recognition task upon local administration of the drug into the NBM area. The intra-NBM administration of RS67333 enhances the acquisition (200–500 ng/0.5 μL) and the consolidation (40–200 ng/0.5 μL) of the place recognition memory. These effects are reversed by pretreatment with the selective 5-HT4 receptor antagonist RS39604 (300 ng/0.5μL). Conversely, the recall of memory is not affected by the 5-HT4 agonist. Our results indicate that 5-HT4 receptors located within the NBM may play a role in spatial memory and that the procognitive effect of RS67333 is due, at least in part, to the potentiation of the activity of cholinergic NBM-cortical pathways. PMID:14557615

  6. Chronic fetal exposure to caffeine altered resistance vessel functions via RyRs-BKCa down-regulation in rat offspring

    PubMed Central

    Li, Na; Li, Yongmei; Gao, Qinqin; Li, Dawei; Tang, Jiaqi; Sun, Miao; Zhang, Pengjie; Liu, Bailin; Mao, Caiping; Xu, Zhice

    2015-01-01

    Caffeine modifies vascular/cardiac contractility. Embryonic exposure to caffeine altered cardiac functions in offspring. This study determined chronic influence of prenatal caffeine on vessel functions in offspring. Pregnant Sprague-Dawley rats (5-month-old) were exposed to high dose of caffeine, their offspring (5-month-old) were tested for vascular functions in mesenteric arteries (MA) and ion channel activities in smooth muscle cells. Prenatal exposure to caffeine increased pressor responses and vasoconstrictions to phenylephrine, accompanied by enhanced membrane depolarization. Large conductance Ca2+-activated K+ (BKCa) channels in buffering phenylephrine-induced vasoconstrictions was decreased, whole cell BKCa currents and spontaneous transient outward currents (STOCs) were decreased. Single channel recordings revealed reduced voltage/Ca2+ sensitivity of BKCa channels. BKCa α-subunit expression was unchanged, BKCa β1-subunit and sensitivity of BKCa to tamoxifen were reduced in the caffeine offspring as altered biophysical properties of BKCa in the MA. Simultaneous [Ca2+]i fluorescence and vasoconstriction testing showed reduced Ca2+, leading to diminished BKCa activation via ryanodine receptor Ca2+ release channels (RyRs), causing enhanced vascular tone. Reduced RyR1 was greater than that of RyR3. The results suggest that the altered STOCs activity in the caffeine offspring could attribute to down-regulation of RyRs-BKCa, providing new information for further understanding increased risks of hypertension in developmental origins. PMID:26277840

  7. AhV_aPA-induced vasoconstriction involves the IP₃Rs-mediated Ca²⁺ releasing.

    PubMed

    Zeng, Fuxing; Zou, Zhisong; Niu, Liwen; Li, Xu; Teng, Maikun

    2013-08-01

    AhV_aPA, the acidic PLA₂ purified from Agkistrodon halys pallas venom, was previously reported to possess a strong enzymatic activity and can remarkably induce a further contractile response on the 60 mM K⁺-induced contraction with an EC₅₀ in 369 nM on mouse thoracic aorta rings. In the present study, we found that the p-bromo-phenacyl-bromide (pBPB), which can completely inhibit the enzymatic activity of AhV_aPA, did not significantly reduce the contractile response on vessel rings induced by AhV_aPA, indicating that the vasoconstrictor effects of AhV_aPA are independent of the enzymatic activity. The inhibitor experiments showed that the contractile response induced by AhV_aPA is mainly attributed to the Ca²⁺ releasing from Ca²⁺ store, especially sarcoplasmic reticulum (SR). Detailed studies showed that the Ca²⁺ release from SR is related to the activation of inositol trisphosphate receptors (IP₃Rs) rather than ryanodine receptors (RyRs). Furthermore, the vasoconstrictor effect could be strongly reduced by pre-incubation with heparin, indicating that the basic amino acid residues on the surface of AhV_aPA may be involved in the interaction between AhV_aPA and the molecular receptors. These findings offer new insights into the functions of snake PLA₂ and provide a novel pathogenesis of A. halys pallas venom.

  8. Accuracy Assessment and Correction of Vaisala RS92 Radiosonde Water Vapor Measurements

    NASA Technical Reports Server (NTRS)

    Whiteman, David N.; Miloshevich, Larry M.; Vomel, Holger; Leblanc, Thierry

    2008-01-01

    Relative humidity (RH) measurements from Vaisala RS92 radiosondes are widely used in both research and operational applications, although the measurement accuracy is not well characterized as a function of its known dependences on height, RH, and time of day (or solar altitude angle). This study characterizes RS92 mean bias error as a function of its dependences by comparing simultaneous measurements from RS92 radiosondes and from three reference instruments of known accuracy. The cryogenic frostpoint hygrometer (CFH) gives the RS92 accuracy above the 700 mb level; the ARM microwave radiometer gives the RS92 accuracy in the lower troposphere; and the ARM SurTHref system gives the RS92 accuracy at the surface using 6 RH probes with NIST-traceable calibrations. These RS92 assessments are combined using the principle of Consensus Referencing to yield a detailed estimate of RS92 accuracy from the surface to the lowermost stratosphere. An empirical bias correction is derived to remove the mean bias error, yielding corrected RS92 measurements whose mean accuracy is estimated to be +/-3% of the measured RH value for nighttime soundings and +/-4% for daytime soundings, plus an RH offset uncertainty of +/-0.5%RH that is significant for dry conditions. The accuracy of individual RS92 soundings is further characterized by the 1-sigma "production variability," estimated to be +/-1.5% of the measured RH value. The daytime bias correction should not be applied to cloudy daytime soundings, because clouds affect the solar radiation error in a complicated and uncharacterized way.

  9. LPA rs10455872 polymorphism is associated with coronary lesions in Brazilian patients submitted to coronary angiography

    PubMed Central

    2014-01-01

    Background Polymorphisms in the LPA gene were associated with coronary artery disease (CAD). However, there are differences in the allelic frequencies, Lp(a) levels, and significant association with CAD according to ethnic groups. In this scenario, the main aim of this study was to assess the influence of the LPA polymorphisms on coronary lesions in Brazilian patients. Methods 1,394 consecutive patients submitted to coronary angiography to study suggestive CAD and twenty coronary segments were scored. Genotyping for the LPA rs10455872 and rs3798220 polymorphisms were performed by high resolution melting analysis. Results The frequencies of the rs10455872 G and rs3798220 C variant alleles were 6.4% and 6.2%, respectively. LPA rs10455872 G variant allele was associated with higher odds ratio of having coronary lesions in an adjusted model (OR = 2.02, 95% CI = 1.10-3.72, p = 0.02). Scores of coronary lesions (extension, severity, and Gensini scores) were significantly different among rs10455872 genotype groups. Coronary lesions was not associated with LPA rs3798220 (OR = 1.09, 95% CI = 0.67-1.76, p = 0.73) and scores of coronary lesions were not different among rs3798220 genotypes. Conclusions We confirmed the association of the LPA rs10455872 with CAD in a large sample of Brazilian patients. For the LPA rs3798220, our finding is consistent with studies which showed the lack of this genetic association. PMID:24776095

  10. Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome.

    PubMed

    Li, Chao; Shi, Yuhua; You, Li; Wang, Laicheng; Chen, Zi-Jiang

    2011-03-01

    The aim of the present study was to determine whether or not the 'melatonin receptor (MTNR1B)' gene polymorphisms are associated with a predisposition for polycystic ovary syndrome (PCOS). The single-nucleotide polymorphisms (SNPs), rs10830963 and rs10830962, in the MTNR1B gene were detected in 526 patients with PCOS and 547 healthy Chinese Han women. The association between MTNR1B gene variants and plasma glucose and insulin levels during the oral glucose tolerance test (OGTT) and hormone levels was investigated. The frequencies of three genotypes and two allelotypes of the SNP, rs10830963, differed significantly between women with PCOS and healthy controls (P < 0.001 and P < 0.001, respectively). The SNP, rs10830963, was significantly associated with higher fasting plasma glucose concentrations (P < 0.001) and increased the area under the curve of plasma glucose levels during the OGTT (P < 0.001), as well as increased homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.027). No significant differences were observed in the genotypes and allele distributions of rs10830962 polymorphisms between the PCOS and the control groups (P = 0.311 and P = 0.178, respectively). There was no significant difference in the clinical and the metabolic characteristics in women with PCOS with different genotypes in the SNP, rs10830962 (all P > 0.005). The present study suggest that the SNP, rs10830963, in the MTNR1B gene is not only associated with susceptibility to PCOS, but also contributes to the PCOS phenotype.

  11. Association of genetic variants in INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) with type 2 diabetes (T2D): a case-control study in three ethnic groups from North-West India.

    PubMed

    Sokhi, Jasmine; Sikka, Ruhi; Raina, Priyanka; Kaur, Ramandeep; Matharoo, Kawaljit; Arora, Punit; Bhanwer, Ajs

    2016-02-01

    Genetic contributions towards Type 2 diabetes (T2D) have been assessed through association studies across different world populations with inconsistencies. The majority of the T2D susceptibility loci are common across different races or populations but show ethnicity-specific differences. The pathogenesis of T2D involves genetic variants in the candidate genes. The interactions between the genes involved in insulin signaling and secretory pathways are believed to play an important role in determining an individual's susceptibility towards T2D. Therefore, the present study was initiated to examine the differences, if any, in the contribution of polymorphisms towards T2D susceptibility in the background of different ethnic specifications. The present case-control study included a total of 1216 T2D cases and healthy controls from three ethnic groups (Jat Sikhs, Banias and Brahmins) of North-West India. Polymorphisms were selected on the basis of information available in the literature for INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) in context to T2D. The genotyping was done using PCR-RFLP method. Statistical analysis was done using SPSS 16.0. The analyses revealed that INS (rs689) polymorphism conferred risk towards T2D susceptibility in all the three ethnic groups whereas INSR (rs1799816) polymorphism conferred risk towards T2D in Brahmins only and PP1G.G (rs1799999) polymorphism indicated T2D risk in Jat Sikhs only. Furthermore, interaction analyses indicated the cumulative role of three genetic variants in modulating T2D susceptibility in the three ethnic groups. In conclusion, our results substantiated the evidences for the role of ethnicity in differential susceptibility to T2D in the background of same genetic variants.

  12. Group I mGluRs increase excitability of hippocampal CA1 pyramidal neurons by a PLC-independent mechanism.

    PubMed

    Ireland, David R; Abraham, Wickliffe C

    2002-07-01

    Previous studies have implicated phospholipase C (PLC)-linked Group I metabotropic glutamate receptors (mGluRs) in regulating the excitability of hippocampal CA1 pyramidal neurons. We used intracellular recordings from rat hippocampal slices and specific antagonists to examine in more detail the mGluR receptor subtypes and signal transduction mechanisms underlying this effect. Application of the Group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) suppressed slow- and medium-duration afterhyperpolarizations (s- and mAHP) and caused a consequent increase in cell excitability as well as a depolarization of the membrane and an increase in input resistance. Interestingly, with the exception of the suppression of the mAHP, these effects were persistent, and in the case of the sAHP lasting for more than 1 h of drug washout. Preincubation with the specific mGluR5 antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), reduced but did not completely prevent the effects of DHPG. However, preincubation with both MPEP and the mGluR1 antagonist LY367385 completely prevented the DHPG-induced changes. These results demonstrate that the DHPG-induced changes are mediated partly by mGluR5 and partly by mGluR1. Because Group I mGluRs are linked to PLC via G-protein activation, we also investigated pathways downstream of PLC activation, using chelerythrine and cyclopiazonic acid to block protein kinase C (PKC) and inositol 1,4,5-trisphosphate-(IP(3))-activated Ca(2+) stores, respectively. Neither inhibitor affected the DHPG-induced suppression of the sAHP or the increase in excitability nor did an inhibitor of PLC itself, U-73122. Taken together, these results argue that in CA1 pyramidal cells in the adult rat, DHPG activates mGluRs of both the mGluR5 and mGluR1 subtypes, causing a long-lasting suppression of the sAHP and a consequent persistent increase in excitability via a PLC-, PKC-, and IP(3)-independent transduction pathway.

  13. The Two-Component System GrvRS (EtaRS) Regulates ace Expression in Enterococcus faecalis OG1RF

    PubMed Central

    Singh, Kavindra V.; La Rosa, Sabina Leanti; Cohen, Ana Luisa V.; Murray, Barbara E.

    2014-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. PMID:25385790

  14. Cephalopods in neuroscience: regulations, research and the 3Rs.

    PubMed

    Fiorito, Graziano; Affuso, Andrea; Anderson, David B; Basil, Jennifer; Bonnaud, Laure; Botta, Giovanni; Cole, Alison; D'Angelo, Livia; De Girolamo, Paolo; Dennison, Ngaire; Dickel, Ludovic; Di Cosmo, Anna; Di Cristo, Carlo; Gestal, Camino; Fonseca, Rute; Grasso, Frank; Kristiansen, Tore; Kuba, Michael; Maffucci, Fulvio; Manciocco, Arianna; Mark, Felix Christopher; Melillo, Daniela; Osorio, Daniel; Palumbo, Anna; Perkins, Kerry; Ponte, Giovanna; Raspa, Marcello; Shashar, Nadav; Smith, Jane; Smith, David; Sykes, António; Villanueva, Roger; Tublitz, Nathan; Zullo, Letizia; Andrews, Paul

    2014-03-01

    Cephalopods have been utilised in neuroscience research for more than 100 years particularly because of their phenotypic plasticity, complex and centralised nervous system, tractability for studies of learning and cellular mechanisms of memory (e.g. long-term potentiation) and anatomical features facilitating physiological studies (e.g. squid giant axon and synapse). On 1 January 2013, research using any of the about 700 extant species of "live cephalopods" became regulated within the European Union by Directive 2010/63/EU on the "Protection of Animals used for Scientific Purposes", giving cephalopods the same EU legal protection as previously afforded only to vertebrates. The Directive has a number of implications, particularly for neuroscience research. These include: (1) projects will need justification, authorisation from local competent authorities, and be subject to review including a harm-benefit assessment and adherence to the 3Rs principles (Replacement, Refinement and Reduction). (2) To support project evaluation and compliance with the new EU law, guidelines specific to cephalopods will need to be developed, covering capture, transport, handling, housing, care, maintenance, health monitoring, humane anaesthesia, analgesia and euthanasia. (3) Objective criteria need to be developed to identify signs of pain, suffering, distress and lasting harm particularly in the context of their induction by an experimental procedure. Despite diversity of views existing on some of these topics, this paper reviews the above topics and describes the approaches being taken by the cephalopod research community (represented by the authorship) to produce "guidelines" and the potential contribution of neuroscience research to cephalopod welfare.

  15. Evaluation of interferon-induced transmembrane protein-3 (IFITM3) rs7478728 and rs3888188 polymorphisms and the risk of pulmonary tuberculosis

    PubMed Central

    Naderi, Mohammad; Hashemi, Mohammad; Abedipour, Fatemeh; Bahari, Gholamreza; Rezaei, Maryam; Taheri, Mohsen

    2016-01-01

    The current study aimed to examine the possible association between the interferon-induced transmembrane protein-3 (IFITM3) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample population. This case-control study was conducted on 188 PTB patients and 169 healthy subjects. The rs7478728 and rs3888188 variants of IFITM3 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The findings showed no significant association between rs7478728 polymorphism and risk of PTB. Regarding rs3888188 polymorphism, the TG genotype as well as G allele significantly increased the risk of PTB [odds ratio (OR)=2.48, 95% confidence interval (CI): 1.42–4.53; P=0.002, and OR=2.26, 95% CI: 1.33–3.86; P=0.003, respectively]. In conclusion, the findings revealed that rs3888188 polymorphism increased the risk of PTB in a sample of Iranian population. Additional investigation with larger sample sizes and different ethnicities are needed to verify our findings. PMID:27882230

  16. Two common functional catalase gene polymorphisms (rs1001179 and rs794316) and cancer susceptibility: evidence from 14,942 cancer cases and 43,285 controls

    PubMed Central

    Wang, Xijing; Kang, Huafeng; Lin, Shuai; Yang, Pengtao; Dai, Cong; Xu, Peng; Li, Shanli; Dai, Zhijun

    2016-01-01

    Recent studies have focused on the associations of catalase polymorphisms with various types of cancer, including cervical and prostate cancers. However, the results were inconsistent. To obtain a more reliable conclusion, we evaluated the relationship between the two common catalase gene polymorphisms (rs1001179 and rs794316) and cancer risk by a meta-analysis. Our meta-analysis included 37 published studies involving 14,942 cancer patients and 43,285 cancer-free controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. The results demonstrated that the rs1001179 polymorphism was associated with an increased cancer risk in the recessive and homozygote models (TT vs. CC: OR = 1.19, P = 0.01; TT vs. CT+CC: OR = 1.19, P <0.001). Furthermore, stratified analyses revealed a significant association between the rs1001179 polymorphism and prostate cancer in all models except the homozygote comparison. An association of the rs794316 polymorphism with cancer risk was detected in two genetic models (TT vs. AA: OR = 1.34, 95% CI = 1.03–1.74, P <0.001; TT vs. AT+AA: OR = 1.39, 95% CI = 1.09–1.77, P = 0.01). Additional well-designed studies with large samples should be performed to validate our results. PMID:27449288

  17. Pioneering better science through the 3Rs: an introduction to the national centre for the replacement, refinement, and reduction of animals in research (NC3Rs).

    PubMed

    Burden, Natalie; Chapman, Kathryn; Sewell, Fiona; Robinson, Vicky

    2015-03-01

    The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is an independent scientific organization that is based in the United Kingdom, which was set up by the government to lead the discovery and application of new technologies and approaches that minimize the use of animals in research and improve animal welfare. The NC3Rs uses a range of strategies to improve and advance science through application of the 3Rs. These include funding basic research, open innovation (CRACK IT), and programs run by inhouse scientists. We present several case studies from the NC3Rs portfolio, featuring asthma research, the use of nonhuman primates in monoclonal antibody development, and CRACK IT. Finally, we anticipate the future, as we use our experience to move into new research fields and expand toward international collaboration. Here we highlight how equipping scientists with relevant and emerging 3Rs tools can help overcome the challenges and limitations of the use of animals in research to the benefit of the whole bioscience community.

  18. Pioneering Better Science through the 3Rs: An Introduction to the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs)

    PubMed Central

    Burden, Natalie; Chapman, Kathryn; Sewell, Fiona; Robinson, Vicky

    2015-01-01

    The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is an independent scientific organization that is based in the United Kingdom, which was set up by the government to lead the discovery and application of new technologies and approaches that minimize the use of animals in research and improve animal welfare. The NC3Rs uses a range of strategies to improve and advance science through application of the 3Rs. These include funding basic research, open innovation (CRACK IT), and programs run by inhouse scientists. We present several case studies from the NC3Rs portfolio, featuring asthma research, the use of nonhuman primates in monoclonal antibody development, and CRACK IT. Finally, we anticipate the future, as we use our experience to move into new research fields and expand toward international collaboration. Here we highlight how equipping scientists with relevant and emerging 3Rs tools can help overcome the challenges and limitations of the use of animals in research to the benefit of the whole bioscience community. PMID:25836967

  19. Signal Perception by the Secretion Stress-Responsive CssRS Two-Component System in Bacillus subtilis

    PubMed Central

    Botella, Eric; Butler, Clodagh; Hansen, Annette; Jende, Inga; Devine, Kevin M.

    2012-01-01

    The CssRS two-component system responds to heat and secretion stresses in Bacillus subtilis by controlling expression of HtrA and HtrB chaperone-type proteases and positively autoregulating its own expression. Here we report on the features of the CssS extracellular loop domain that are involved in signal perception and on CssS subcellular localization. Individual regions of the CssS extracellular loop domain contribute differently to signal perception and activation. The conserved hydrophilic 26-amino-acid segment juxtaposed to transmembrane helix 1 is involved in the switch between the deactivated and activated states, while the conserved 19-amino-acid hydrophobic segment juxtaposed to transmembrane 2 is required for signal perception and/or transduction. Perturbing the size of the extracellular loop domain increases CssS kinase activity and makes it unresponsive to secretion stress. CssS is localized primarily at the septum but is also found in a punctate pattern with lower intensity throughout the cell cylinder. Moreover, the CssRS-controlled HtrA and HtrB proteases are randomly distributed in foci throughout the cell surface, with more HtrB than HtrA foci in unstressed cells. PMID:22307758

  20. In vitro and in vivo properties of (/sup 125/I) (R,S) 4IQNB: A lower affinity diastereomeric muscarinic receptor radiotracer

    SciTech Connect

    Gibson, R.E.; Schneidau, T.A.; Rzeszotarski, W.J.; Cohen, V.I.; Eckelman, W.C.; Reba, R.C.

    1985-05-01

    The (R,R) diastereomer of 3-Quinuclidinyl 4-Iodobenzilate (4IQNB) is a high affinity muscarinic acetylcholine receptor radiotracer which has provided images of receptor distribution in the CNS of man. The radiotracer is of such high affinity that dissociation in vivo is not evident in man after 6-half-lives I-123. Since the dissociation kinetics of radiotracer may be helpful for receptor quantitation, the authors have prepared (/sup 125/I) (R,S) 4IQNB: a diastereomer of 4IQNB which as a lower affinity for the m-AChR than the (R,R) isomer. The equilibrium association constant for the (R,S) diastereomer is 1.10 x 10/sup 9/ M/sup -1/, which is 4-fold lower in affinity than (/sup 3/H) (R) QNB and 2-fold lower than that of the (R,R) 4IQNB. Of more interest, the dissociation rate constant of (R,S) 4IQNB is 0.099 (+0.01)/min., 15-fold more rapid than that of the (R,R) isomer. The systemic distribution of (R,S) 4IQNB is similar to that of (R,R) 4IQNB except localization in the myocardium is 2-fold lower, reflecting the lower affinity. Nonreceptor interactions are the same since the compounds differ only as optical isomers around the carbinol chiral center. In the CNS peak activities are obtained in the corpus striatum (and other M/sub 1/-receptor rich structures) which are the same as obtained with (R,R) 4IQNB. However, no washout of (R,R) 4IQNB is observed after 4 hrs and only 60% in 24 hrs. By contrast, 65% of (R,S) 4IQNB washes out in 4 hrs and no significant activity is detected after 24 hrs. The increased washout kinetics should provide a better radiotracer for determining muscarinic receptor concentrations in the CNS of man.

  1. The RS685012 Polymorphism of ACCN2, the Human Ortholog of Murine Acid-Sensing Ion Channel (ASIC1) Gene, is Highly Represented in Patients with Panic Disorder.

    PubMed

    Gugliandolo, Agnese; Gangemi, Chiara; Caccamo, Daniela; Currò, Monica; Pandolfo, Gianluca; Quattrone, Diego; Crucitti, Manuela; Zoccali, Rocco Antonio; Bruno, Antonio; Muscatello, Maria Rosaria Anna

    2016-03-01

    Panic disorder (PD) is a disabling anxiety disorder that is characterized by unexpected, recurrent panic attacks, associated with fear of dying and worrying about possible future attacks or other behavioral changes as a consequence of the attacks. The acid-sensing ion channels (ASICs) are a family of proton-sensing channels expressed throughout the nervous system. Their activity is linked to a variety of behaviors including fear, anxiety, pain, depression, learning, and memory. The human analog of ASIC1a is the amiloride-sensitive cation channel 2 (ACCN2). Adenosine A2A receptors are suggested to play an important role in different brain circuits and pathways involved in anxiety reactions. In this work we aimed to evaluate the distribution of ACCN2 rs685012 and ADORA2A rs2298383 polymorphisms in PD patients compared with healthy subjects. We found no association between ADORA2A polymorphism and PD. Instead, the C mutated allele for ACCN2 rs685012 polymorphism was significantly more frequent in patients than in controls. On the contrary, the TT homozygous wild-type genotype and also the ACCN2 TT/ADORA2A CT diplotype were significantly more represented in controls. These results are suggestive for a role of ACCN2 rs685012 polymorphism in PD development in Caucasian people.

  2. Association of KIR2DL2 polymorphism rs2756923 with type 1 diabetes and preliminary evidence for lack of inhibition through HLA-C1 ligand binding.

    PubMed

    Ramos-Lopez, E; Scholten, F; Aminkeng, F; Wild, C; Kalhes, H; Seidl, C; Tonn, T; Van der Auwera, B; Badenhoop, K

    2009-06-01

    Killer cell immunoglobulin-like receptors (KIRs) on chromosome 19q13.4 regulate the function of not only human natural killer (NK) cells but also T cells. An increase in activating KIR- human leucocyte antigen ligand pairs has been associated with an additional risk to develop type 1 diabetes (T1D). T1D families [n = 184 (552 individuals); n = 176 (528 subjects)], unrelated T1D patients (n = 380; n = 394) and healthy controls (n = 315; n = 401) from Germany and Belgium, respectively, were genotyped for the rs2756923 polymorphism within the KIR gene cluster haplotype B in exon 8 of the KIR2DL2 gene. We observed in both Germans and Belgians an overtransmission of the allele 'G' of the KIR2DL2-rs2756923 polymorphism (64.2% vs 35.8%, P = 3 x 10(-4) and 60.0% vs 40.0%, P = 0.02, respectively). In addition, this allele was more frequent in German patients than in healthy controls (78.4% vs 21.6%, P = 1 x 10(-3)). Preliminary results from a cytotoxicity assay suggest that inhibition of NK-cell cytotoxicity may be impaired in individuals carrying the rs2756923 G allele. These data suggest a potential role of the KIR2DL2-rs2756923 polymorphism in T1D in Germans and Belgians.

  3. LINGO1 rs9652490 is associated with essential tremor and Parkinson disease.

    PubMed

    Vilariño-Güell, Carles; Ross, Owen A; Wider, Christian; Jasinska-Myga, Barbara; Cobb, Stephanie A; Soto-Ortolaza, Alexandra I; Kachergus, Jennifer M; Keeling, Brett H; Dachsel, Justus C; Melrose, Heather L; Behrouz, Bahareh; Wszolek, Zbigniew K; Uitti, Ryan J; Aasly, Jan O; Rajput, Alex; Farrer, Matthew J

    2010-02-01

    Recently, a variant in LINGO1 (rs9652490) was found to associate with increased risk of essential tremor. We set out to replicate this association in an independent case-control series of essential tremor from North America. In addition, given the clinical and pathological overlap between essential tremor and Parkinson disease, we also evaluate the effect of LINGO1 rs9652490 in two case-control series of Parkinson disease. Our study demonstrates a significant association between LINGO1 rs9652490 and essential tremor (P = 0.014) and Parkinson disease (P = 0.0003), thus providing the first evidence of a genetic link between both diseases.

  4. RS-34 (Peacekeeper Post Boost Propulsion System) Orbital Debris Application Concept Study

    NASA Technical Reports Server (NTRS)

    Esther, Elizabeth A.; Burnside, Christopher G.

    2013-01-01

    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) lead a study to evaluate the Rocketdyne produced RS-34 propulsion system as it applies to an orbital debris removal design reference mission. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program; specifically the pressure-fed storable bi-propellant Stage IV Post Boost Propulsion System. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. Subsequently, MSFC is working closely with the USAF to obtain all the remaining RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. Originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Concept Study, preceded by a utilization study to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions, sought to further understand application for an orbital debris design reference mission as the orbital debris removal mission was found to closely mimic the heritage RS-34 mission. The RS-34 Orbital Debris Application Concept Study sought to identify multiple configurations varying the degree of modification to trade for dry mass optimization and propellant load for overall capability and evaluation of several candidate missions. The results of the RS-34 Phoenix Utilization Study show that the system is technically sufficient to successfully support all of the missions

  5. Genome-wide association study-identified SNPs (rs3790844, rs3790843) in the NR5A2 gene and risk of pancreatic cancer in Japanese

    PubMed Central

    Ueno, Makoto; Ohkawa, Shinichi; Morimoto, Manabu; Ishii, Hiroshi; Matsuyama, Masato; Kuruma, Sawako; Egawa, Naoto; Nakao, Haruhisa; Mori, Mitsuru; Matsuo, Keitaro; Hosono, Satoyo; Nojima, Masanori; Wakai, Kenji; Nakamura, Kozue; Tamakoshi, Akiko; Takahashi, Mami; Shimada, Kazuaki; Nishiyama, Takeshi; Kikuchi, Shogo; Lin, Yingsong

    2015-01-01

    We genotyped 2 SNPs (rs3790844 T/C and rs3790843 G/A) in the NR5A2 gene that were identified in a genome-wide association study (GWAS) of pancreatic cancer in populations of mainly European ancestry, and we examined their associations with pancreatic cancer risk in a case-control study of 360 patients and 400 control subjects in Japan. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The SNPs were in linkage disequilibrium (r2 = 0.80). For rs3790843, the multivariable-adjusted OR was 0.75 (95% CI: 0.41–1.36) and 0.60 (95%CI: 0.33–1.08) for subjects with the AG and AA genotype, respectively, compared to subjects with the GG genotype. The per allele OR was 0.78 (0.62–0.99) (P = 0.046). For rs3790844, the multivariable-adjusted OR was 0.65 (95% CI: 0.37–1.14) and 0.47 (95%CI: 0.27–0.83) for subjects with the CT and CC genotype, respectively, compared to subjects with the TT genotype. The per allele OR was 0.70 (0.56–0.89) (P = 0.003). Our case-control study found that rs3790843 and rs3790844 in the NR5A2 gene are associated with pancreatic cancer risk in Japanese subjects. The direction of association is consistent with the prior findings from GWASs. PMID:26592175

  6. Role of TLR4  rs4986790A>G and rs4986791C>T Polymorphisms in the Risk of Inflammatory Bowel Disease

    PubMed Central

    Ao, Ran; Wang, Ying; Zhnag, Dao-Rong; Du, Ya-Qi

    2015-01-01

    Objective. The present meta-analysis investigated the contribution of TLR4 rs4986790A>G and rs4986791C>T genetic polymorphisms in increasing the risk of inflammatory bowel disease (IBD). Methods. Databases were searched using a combination of keywords related to TLR4 and IBD. Relevant studies were selected based on strict inclusion and exclusion criteria. Meta-analysis of the data extracted from the selected studies was performed using CMA 2.0 statistical analysis software. Results. Out of the 70 studies retrieved by database search, only 13 studies were eligible for inclusion in this meta-analysis and these 13 studies contained a total number of 4409 IBD patients and 5693 healthy controls. The meta-analysis results demonstrated that TLR4 rs4986790A>G polymorphism is associated with an increased risk of IBD (allele model: OR = 1.268, 95% CI = 1.124~1.431, and P < 0.001; dominant model: OR = 1.240, 95% CI = 1.090~1.409, and P = 0.001). Similarly, TLR4 rs4986791C>T polymorphism also conferred an increased risk of IBD (allele model: OR = 1.259, 95% CI = 1.092~1.453, and P = 0.002; dominant model: OR = 1.246, 95% CI = 1.072~1.447, and P = 0.004). Conclusion. Our meta-analysis results demonstrate that TLR4 rs4986790A>G and rs4986791C>T genetic polymorphisms are associated with the etiopathogenesis of IBD. PMID:26089865

  7. Construction, expression, and characterization of Arabidopsis thaliana 4CL and Arachis hypogaea RS fusion gene 4CL::RS in Escherichia coli.

    PubMed

    Zhang, Erhao; Guo, Xuefeng; Meng, Zhifen; Wang, Jin; Sun, Jia; Yao, Xi; Xun, Hang

    2015-09-01

    Resveratrol is an important antioxidant that confers several beneficial effects on human health. 4-coumarate coenzyme A ligase (4CL) and resveratrol synthase (RS) are key rate-limiting enzymes in the biosynthetic pathway of resveratrol. Using gene fusion technology, the fusion gene, 4CL::RS, was constructed by the 4CL gene from Arabidopsis thaliana and RS gene from Arachis hypogaea. DNAMAN analysis showed that the fusion gene encoded a 964-amino acid protein with an approximate weight of 104.7 kDa and a pI of 5.63. A prokaryotic expression vector containing Nco-I and EcoR-I restriction sites, pET-30a/4CL::RS, was identified by liquid culture bacterial PCR, enzyme digestion, and sequencing, and then used in the induction of expression. Subsequently, a biosynthetic pathway of resveratrol was constructed in Escherichia coli BL21(DE3) that harbored pET-30a/4CL::RS. The recombinant strains were induced to express the fusion protein at 28 °C for 8 h. After bacterial cells were disrupted by hypothermic ultrasonication, the 4CL::RS fusion protein was thoroughly separated from tags using Ni-NTA affinity chromatography, and then detected by SDS-PAGE analysis. When the recombinant strains expressed the fusion protein, the precursor, p-coumaric acid, was converted to resveratrol. In the present study, the final concentration of resveratrol derived from 1 mM p-coumaric acid was 80.524 mg/L, with a 35.28 % (mol/mol) conversion yield.

  8. 75 FR 44051 - Resolicitation of Applications for the Railroad Safety Technology Program Grant Program (RS-TEC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... Grant Program (RS-TEC-10-001) AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Notice of Funds Availability, Resolicitation of Applications (RS-TEC-10-001... Railroad Safety Technology Grant Program ] (Funding Opportunity RS-TEC-10-001), the Federal...

  9. The FTO gene polymorphism (rs9939609) is associated with metabolic syndrome in morbidly obese subjects from southern Italy.

    PubMed

    Liguori, Rosario; Labruna, Giuseppe; Alfieri, Andreina; Martone, Domenico; Farinaro, Eduardo; Contaldo, Franco; Sacchetti, Lucia; Pasanisi, Fabrizio; Buono, Pasqualina

    2014-08-01

    Gene variants in MC4R, SIRT1 and FTO are associated with severe obesity and metabolic impairment in Caucasians. We investigated whether common variants in these genes are associated with metabolic syndrome (MetS) in a large group of morbidly obese young adults from southern Italy. One thousand morbidly obese subjects (62% women, mean body mass index 46.5 kg/m(2), mean age 32.6 years) whose families had lived in southern Italy for at least 2 generations were recruited. Single-nucleotide polymorphisms (SNPs) rs12970134, rs477181, rs502933 (MC4R locus), rs3818292, rs7069102, rs730821, rs2273773, rs12413112 (SIRT1 locus) and rs1421085, rs9939609, 9930506, 1121980 (FTO locus) were genotyped by Taqman assay; blood parameters were assayed by routine methods; the Fat Mass, Fat Free Mass, Respiratory Quotient, Basal Metabolic Rate (BMR) and waist circumference were also determined. Binomial logistic regression showed that the TA heterozygous genotype of SNP rs9939609 in the FTO gene was associated with the presence of MetS in our population [OR (95% CI): 2.53 (1.16-5.55)]. Furthermore, the FTO rs9939609 genotype accounted for 21.3% of the MetS phenotype together with total cholesterol, BMR and age. Our results extend the knowledge on genotype susceptibility for MetS in relation to a specific geographical area of residence.

  10. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    NASA Astrophysics Data System (ADS)

    Anh, Nguyen Tuan; Chi, Nguyen T.; Khai Tran, T.; Tuyen Dao, T. P.; Nhan Le, N. T.; Mau Chien, Dang; Hoai, Nguyen To

    2012-12-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

  11. Consideration and Checkboxes: Incorporating Ethics and Science into the 3Rs

    PubMed Central

    Landi, Margaret S; Shriver, Adam J; Mueller, Anne

    2015-01-01

    Members of the research community aim to both produce high-quality research and ensure that harm is minimized in animals. The primary means of ensuring these goals are both met is the 3Rs framework of replacement, reduction, and refinement. However, some approaches to the 3Rs may result in a ‘check box mentality’ in which IACUC members, researchers, administrators, and caretakers check off a list of tasks to evaluate a protocol. We provide reasons for thinking that the 3Rs approach could be enhanced with more explicit discussion of the ethical assumptions used to arrive at an approved research protocol during IACUC review. Here we suggest that the notion of moral considerability, and all of the related issues it gives rise to, should be incorporated into IACUC discussions of 3Rs deliberations during protocol review to ensure that animal wellbeing is enhanced within the constraints of scientific investigation. PMID:25836970

  12. The gender-specific association of rs334558 in GSK3β with major depressive disorder

    PubMed Central

    Liu, Sha; Wang, Le; Sun, Ning; Yang, Chunxia; Liu, Zhifen; Li, Xinrong; Cao, Xiaohua; Xu, Yong; Zhang, Kerang

    2017-01-01

    Abstract Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with a heritability ranging from 40% to 50%. The single nucleotide polymorphism (SNP) rs334558 on the glycogen synthase kinase-3β (GSK3β) gene has been identified as a genetic risk loci associated with schizophrenia and bipolar disorder. However, results from replication studies examining the association between rs334558 and MDD remain inconsistent. In the present study, first, we conducted a meta-analysis of the association between rs334558 and MDD by combining 5 available case-control samples totaling 2311 cases and 2535 controls. Second, genotyping data from patients with MDD at our institution, after further stratification by gender, were analyzed to determine the association between rs334558 and MDD. All studies retrieved and included in the meta-analysis were from Korea and China. The meta-analysis suggested that the functional polymorphism rs334558 within the GSK3β promoter region was associated with MDD risk (P < 0.05). The associations were observed both in the allelic and genetic models. Analysis of the genotyping data extracted from our hospital database revealed that rs334558 exhibited exclusive association with MDD in female patients (P=0.015). Our findings suggest that GSK3β rs334558 polymorphisms might be a potential risk for MDD, and females with GSK3β rs334558 polymorphisms might have higher penetrance of MDD. If validated in larger scale samples and in different ethnic populations, these findings might be of value as diagnostic references for MDD. PMID:28099358

  13. Association between MC4R rs17782313 Polymorphism and Overeating Behaviours

    PubMed Central

    Yilmaz, Zeynep; Davis, Caroline; Loxton, Natalie J.; Kaplan, Allan S.; Levitan, Robert D.; Carter, Jacqueline C.; Kennedy, James L.

    2014-01-01

    Background/Objectives Melanocortins play a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behaviour, and depressed mood. Subjects/Methods We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviours was obtained during the in-person assessment. Results BMI was associated with rs17782313 C allele; however this finding did not survive correction for multiple testing (p=0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviours, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n=152). Conclusions To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behaviour, as well as to demonstrate possible mechanisms behind MC4R’s influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating. PMID:24827639

  14. Survey of Canadian animal-based researchers' views on the Three Rs: replacement, reduction and refinement.

    PubMed

    Fenwick, Nicole; Danielson, Peter; Griffin, Gilly

    2011-01-01

    The 'Three Rs' tenet (replacement, reduction, refinement) is a widely accepted cornerstone of Canadian and international policies on animal-based science. The Canadian Council on Animal Care (CCAC) initiated this web-based survey to obtain greater understanding of 'principal investigators' and 'other researchers' (i.e. graduate students, post-doctoral researchers etc.) views on the Three Rs, and to identify obstacles and opportunities for continued implementation of the Three Rs in Canada. Responses from 414 participants indicate that researchers currently do not view the goal of replacement as achievable. Researchers prefer to use enough animals to ensure quality data is obtained rather than using the minimum and potentially waste those animals if a problem occurs during the study. Many feel that they already reduce animal numbers as much as possible and have concerns that further reduction may compromise research. Most participants were ambivalent about re-use, but expressed concern that the practice could compromise experimental outcomes. In considering refinement, many researchers feel there are situations where animals should not receive pain relieving drugs because it may compromise scientific outcomes, although there was strong support for the Three Rs strategy of conducting animal welfare-related pilot studies, which were viewed as useful for both animal welfare and experimental design. Participants were not opposed to being offered "assistance" to implement the Three Rs, so long as the input is provided in a collegial manner, and from individuals who are perceived as experts. It may be useful for animal use policymakers to consider what steps are needed to make replacement a more feasible goal. In addition, initiatives that offer researchers greater practical and logistical support with Three Rs implementation may be useful. Encouragement and financial support for Three Rs initiatives may result in valuable contributions to Three Rs knowledge and improve

  15. Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects.

    PubMed

    Ong, Hing-Huat; Tan, Yen-Nee; Say, Yee-How

    2017-01-01

    We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity.

  16. The Two-Component Signal Transduction System CopRS of Corynebacterium glutamicum Is Required for Adaptation to Copper-Excess Stress

    PubMed Central

    Schelder, Stephanie; Zaade, Daniela; Litsanov, Boris; Bott, Michael; Brocker, Melanie

    2011-01-01

    Copper is an essential cofactor for many enzymes but at high concentrations it is toxic for the cell. Copper ion concentrations ≥50 µM inhibited growth of Corynebacterium glutamicum. The transcriptional response to 20 µM Cu2+ was studied using DNA microarrays and revealed 20 genes that showed a ≥ 3-fold increased mRNA level, including cg3281-cg3289. Several genes in this genomic region code for proteins presumably involved in the adaption to copper-induced stress, e. g. a multicopper oxidase (CopO) and a copper-transport ATPase (CopB). In addition, this region includes the copRS genes (previously named cgtRS9) which encode a two-component signal transduction system composed of the histidine kinase CopS and the response regulator CopR. Deletion of the copRS genes increased the sensitivity of C. glutamicum towards copper ions, but not to other heavy metal ions. Using comparative transcriptome analysis of the ΔcopRS mutant and the wild type in combination with electrophoretic mobility shift assays and reporter gene studies the CopR regulon and the DNA-binding motif of CopR were identified. Evidence was obtained that CopR binds only to the intergenic region between cg3285 (copR) and cg3286 in the genome of C. glutamicum and activates expression of the divergently oriented gene clusters cg3285-cg3281 and cg3286-cg3289. Altogether, our data suggest that CopRS is the key regulatory system in C. glutamicum for the extracytoplasmic sensing of elevated copper ion concentrations and for induction of a set of genes capable of diminishing copper stress. PMID:21799779

  17. NEW EVIDENCE OF MAGNETIC INTERACTIONS BETWEEN STARS FROM THREE-DIMENSIONAL DOPPLER TOMOGRAPHY OF ALGOL BINARIES: {beta} PER AND RS VUL

    SciTech Connect

    Richards, Mercedes T.; Agafonov, Michail I.; Sharova, Olga I. E-mail: agfn@nirfi.sci-nnov.ru

    2012-11-20

    Time-resolved H{alpha} spectra of magnetically active interacting binaries have been used to create three-dimensional (3D) Doppler tomograms by means of the Radioastronomical Approach. This is the first 3D reconstruction of {beta} Per, with RS Vul for comparison. These 3D tomograms have revealed evidence of the mass transfer process (gas stream, circumprimary emission, localized region, absorption zone), as well as loop prominences and coronal mass ejections (CMEs) in {beta} Per and RS Vul that could not be discovered from two-dimensional tomograms alone. The gas stream in both binaries may have been deflected beyond the central plane by the donor star's magnetic field. The stream was more elongated along the predicted trajectory in RS Vul than in {beta} Per, but not as pronounced as in U CrB (stream state). The loop prominence reached maximum V{sub z} velocities of {+-}155 km s{sup -1} in RS Vul compared to {+-}120 km s{sup -1} in {beta} Per, while the CME reached a maximum V{sub z} velocity of +150 km s{sup -1} in RS Vul and +100 km s{sup -1} in {beta} Per. The 3D tomograms show that the gas flows are not symmetric relative to the central plane and are not confined to that plane, a result confirmed by recent 15 GHz VLBI radio images of {beta} Per. Both the 3D H{alpha} tomography and the VLBI radio images support an earlier prediction of the superhump phenomenon in {beta} Per: that the gas between the stars is threaded with a magnetic field even though the hot B8V mass-gaining star is not known to have a magnetic field.

  18. Association between JAK2 rs4495487 Polymorphism and Risk of Budd-Chiari Syndrome in China

    PubMed Central

    Zhang, Peijin; Zhang, Yanyan; Zhang, Jing; Wang, Hui; Ma, He; Wang, Wei; Gao, Xiuyin; Xu, Hao; Lu, Zhaojun

    2015-01-01

    Myeloproliferative neoplasms (MPNs) are the leading cause of Budd-Chiari syndrome (BCS), and the C allele of JAK2 rs4495487 was reported to be an additional candidate locus that contributed to MPNs. In the present study, we examined the role of JAK2 rs4495487 in the etiology and clinical presentation of Chinese BCS patients. 300 primary BCS patients and 311 healthy controls were enrolled to evaluate the association between JAK2 rs4495487 polymorphism and risk of BCS. All subjects were detected for JAK2 rs4495487 by real-time PCR. Results. The JAK2 rs4495487 polymorphism was associated with JAK2 V617F-positive BCS patients compared with controls (P < 0.01). The CC genotype increased the risk of BCS in patients with JAK2 V617F mutation compared with individuals presenting TT genotype (OR = 13.60, 95% CI = 2.04–90.79) and non-CC genotype (OR = 12.00, 95% CI = 2.07–69.52). We also observed a significantly elevated risk of combined-type BCS associated with CC genotype in the recessive model (OR = 4.44, 95% CI = 1.31–15.12). This study provides statistical evidence that the JAK2 rs4495487 polymorphism is susceptibility factor JAK2 V617F positive BCS and combined BCS in China. Further larger studies are required to confirm these findings. PMID:26557140

  19. The Use of Systematic Reviews and Reporting Guidelines to Advance the Implementation of the 3Rs

    PubMed Central

    Avey, Marc T; Fenwick, Nicole; Griffin, Gilly

    2015-01-01

    In 1959, Russell and Burch published The Principles of Humane Experimental Technique, which included concrete advice on factors that they considered would govern progress in the implementation of these principles (enunciated as the 3Rs [Replacement, Reduction, and Refinement in animal-based studies]). One challenge to the implementation of the 3Rs was identified as information retrieval. Here, we further explore this challenge—the need for ‘research on research’—and the role that systematic reviews and reporting guidelines can play in implementation of the 3Rs. First, we examine the 2-fold nature of the challenge of information retrieval: 1) the identification of relevant publications spread throughout a large population of nonrelevant publications and 2) the incomplete reporting of relevant details within those publications. Second, we evaluate how systematic reviews and reporting guidelines can be used generally to address this challenge. Third, we assess the explicit reporting of the 3Rs in a cohort of preclinical animal systematic reviews. Our results show that Reduction methods are the most commonly reported by authors of systematic reviews but that, in general, reporting on how findings relate to the 3Rs is limited at best. Although systematic reviews are excellent tools for resolving the challenge of information retrieval, their utility for making progress in implementation of the 3Rs may be limited unless authors improve their reporting of these principles. PMID:25836961

  20. Association Between MIF-AS rs755622 and Nephrolithiasis Risk in a Chinese Population.

    PubMed

    Ma, Gaoxiang; Yuan, Qinbo; Wang, Qiangdong; Du, Mulong; Chu, Haiyan; Dong, Zhenjia; Xiao, Xu; Wang, Meilin; Qin, Chao; Yin, Changjun; Zhang, Zhengdong; Zhang, Wei

    2016-02-20

    BACKGROUND Single-nucleotide polymorphisms (SNPs) located at lncRNA may affect the stability and splicing processes of mRNA formation, which result in the alteration of its interacting partners. The SNP rs755622 within exon of antisense lncRNA MIF- AS and promoter of MIF was implicated in renal disease risk. MATERIAL AND METHODS In this case-control study, we genotyped the SNP rs755622 in 230 patients diagnosed with nephrolithiasis and 250 controls in a Chinese population. RESULTS We found that the rs755622 CG and CC genotypes had a significantly increased nephrolithiasis risk (adjusted OR=1.52, 95% CI=1.03-2.25; OR=2.63, 95% CI=1.21-5.72, P=0.015), compared with GG genotype in the additive model. The rs755622 C carriers (GC/CC) had an adjusted OR (95% CI) of 1.65 (1.14-2.39, P=0.016), compared with the GG genotype in the dominant model. This hazardous effect was more pronounced in subgroup age >46, BMI >24, hypertension, ever smoking, and ever drinking subjects. Moreover, we found that rs755622 could modulate the function of MIF-AS by influencing its folding. CONCLUSIONS These results indicate that the MIF-AS rs755622 polymorphism may have a crucial role in the development of nephrolithiasis.

  1. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4... operation provided exposed food has been covered or removed from the area being treated prior to...

  2. 40 CFR 180.545 - Prallethrin (RS)-2-methyl-4-oxo-3-(2-propynyl)cyclopent-2-enyl (1RS)-cis, trans-chrysanthemate...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.545 Prallethrin (RS)-2-methyl-4... operation provided exposed food has been covered or removed from the area being treated prior to...

  3. CIITA rs4774 and rs6498122 polymorphisms are associated with oral lichen planus in Chinese people: a case-control study.

    PubMed

    Wu, Dan; Wang, Lifeng; Sun, Mao; Wang, Guoxia; Fu, Shanmin; Dong, Guangying; Wu, Yuanming

    2013-04-01

    Oral lichen planus (OLP) is a common autoimmune inflammatory disorder that is difficult to cure, and its pathogenesis is still largely unknown. The major histocompatibility complex (MHC) class II transactivator (CIITA) gene has been reported to be an important candidate in some classical autoimmune diseases, and certain single nucleotide polymorphisms (SNPs) in CIITA have been confirmed to be associated with susceptibility to some autoimmune diseases. We conducted this research to investigate the existence of any correlation between OLP and SNPs in CIITA. A case-control study was performed to genotype 15 SNPs in the CIITA gene from 42 patients with OLP and from 86 controls; this was carried out by the PCR and then by a locus-specific single-base extension reaction. Allele detection was performed using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The SNP rs4774 variant in exon 11 (+1614G/C, Gly500Ala) of CIITA is significantly associated with OLP in healthy persons, both in genotype frequency and in allele frequency. Another intronic SNP, rs6498122, showed significant differences only in allele frequency. In conclusion, our data show that the two SNPs rs4774 and rs6498122 are associated with OLP and could also indicate the autoimmune characteristics of OLP.

  4. Testing and performance evaluation of T1000G/RS-14 graphite/polycyanate composite materials

    SciTech Connect

    Starbuck, J.M.

    1997-01-01

    The performance of a graphite fiber/polycyanate matrix composite material system, T1000G/RS-14, was evaluated by performing an extensive mechanical property test program. The test program included both static strength and long-term tests for creep, fatigue, and stress rupture. The system was evaluated at both ambient temperature and elevated temperatures. The specimens were machined from composite cylinders that had a unidirectional layup with all the fibers oriented in the hoop direction. The cylinders were fabricated using the wet-filament winding process. In general, the T1000G/RS-14 system demonstrated adequate static strengths for possible aerospace structural applications. The results from the static tests indicated that very high composite hoop tensile strengths can be achieved with this system at both ambient and elevated temperatures as high as 350{degree}F. However, in the long-term testing for compressive creep and tension-tension fatigue the results indicated a lower elevated temperature was required to minimize the risk of using this material system. Additional testing and analysis activities led to the selection of 275{degree}F as the desired temperature for future performance evaluation. Subsequent testing efforts for determining the resin and composite transverse compressive creep responses at 275{degrees}F indicated that excessive creep strain rates may still be a weakness of this system. In the long-term tests, sufficient data was generated from impregnated strand and composite ring stress-life testing, and composite ring tension-tension fatigue to determine failure probabilities for a given set of design requirements. The statistical analyses of the test data, in terms of determining failure probability curves, will be reported on in a separate report. However, it is expected that this material system will have a very low failure probability for stress rupture based on the collected stress-life data. Material responses that will require further

  5. Discovery of non-radial pulsations in the spectroscopic binary Herbig Ae star RS Chamaeleontis

    NASA Astrophysics Data System (ADS)

    Böhm, T.; Zima, W.; Catala, C.; Alecian, E.; Pollard, K.; Wright, D.

    2009-04-01

    Context: To understand the origin of stellar activity in pre-main-sequence Herbig Ae/Be stars and to get a deeper insight into the interior of these enigmatic stars, the pulsational instability strip of Palla and Marconi is investigated. In this article we present a first discovery of non radial pulsations in the Herbig Ae spectroscopic binary star RS Cha. Aims: The goal of the present work is to detect non-radial pulsations in a Herbig Ae star for the first time directly by spectrographic means and to identify the largest amplitude pulsation modes. Methods: The spectroscopic binary Herbig Ae star RS Cha was monitored in quasi-continuous observations during 14 observing nights (Jan. 2006) at the 1 m Mt. John (New Zealand) telescope with the Hercules high-resolution echelle spectrograph. The cumulative exposure time on the star was 44 h, corresponding to 255 individual high-resolution echelle spectra with R = 45 000. Least-square deconvolved spectra (LSD) were obtained for each spectrum, representing the effective photospheric absorption profile modified by pulsations. Difference spectra were calculated by subtracting rotationally broadened artificial profiles, these residual spectra were analysed and non-radial pulsations detected. A subsequent analysis with two complementary methods, namely Fourier Parameter Fit (FPF) and Fourier 2D (F2D) has been performed and first constraints on the pulsation modes derived. Results: For the very first time, we discovered by direct observational means using high-resolution echelle spectroscopy, non-radial oscillations in a Herbig Ae star. In fact, both components of the spectroscopic binary are Herbig Ae stars and both show NRPs. The FPF method identified 2 modes for the primary component with (degree ℓ, azimuthal order m) couples ordered by decreasing probability: f1 = 21.11 d-1 with (ℓ, m) = (11, 11), (11, 9) or (10, 6) and f2 = 30.38 d-1 with (ℓ, m) = ( 10, 6) or (9, 5). The F2D analysis indicates for f1 a degree

  6. C677T (RS1801133 ) MTHFR gene polymorphism frequency in a colombian population

    PubMed Central

    Gómez-Gutierrez, Alberto; Gómez, Piedad Elena; Casas-Gomez, Maria Consuelo; Briceño, Ignacio

    2015-01-01

    Introduction: Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy. Objective: To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals. Methods: Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics®). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed. Results: Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001). Conclusions: Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies. PMID:26309343

  7. Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

    PubMed Central

    Henderson, Brandon J.; Wall, Teagan R.; Henley, Beverley M.; Kim, Charlene H.; Nichols, Weston A.; Moaddel, Ruin; Xiao, Cheng

    2016-01-01

    Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway. SIGNIFICANCE STATEMENT Menthol, the most popular flavorant for tobacco products, has been considered simply a benign flavor additive. However, as we show here

  8. ROSAT all-sky survey observations of X-ray variability in cool giant stars

    NASA Technical Reports Server (NTRS)

    Haisch, Bernhard; Schmitt, J. H. M. M.

    1994-01-01

    We have identified 24 active late-type giant stars, including 11 RS CVn systems, with soft X-ray count rates high enough to allow the detection of statistically significant variability on a Roentgen Satellite (ROSAT) orbital timescale (96 minutes) as observed by the Position Sensitive Proportional Counter (PSPC) during the all-sky survey. Our sensitivity typically lies in the range of 10% - 25%, depending on the source count rate. Comparison is made to the daily, nonflare solar soft X-ray variability as observed by the Solrad satellites during solar minimum in 1969 and solar maximum in 1975. Seven of the 24 stars show significant variability; in two of these cases (HR 3922 and HR 8448) major flares were observed in which the peak count rate is enhanced by at least a factor of 3 above quiescent. While HR 3922 (G5 III) is not (yet) classified as an RS CVn star, its flare is more energetic (3 x 10(exp 31) ergs/s) than previously observed RS CVn flares. The apparently single giant HR 8167 (G8 III) also shows two flares. While one might expect to find an anticorrelation between saturated coronae and variability, we find no evidence of this: the two stars in our sample with the highest ratio of f(sub x)/f(sub v) both show variability. We also point out that Capella (G6 III + F9 III) is one of the stars manifesting variability.

  9. Simulation of Arrhythmogenic Effect of Rogue RyRs in Failing Heart by Using a Coupled Model

    PubMed Central

    Lu, Luyao; Xia, Ling; Zhu, Xiuwei

    2012-01-01

    Cardiac cells with heart failure are usually characterized by impairment of Ca2+ handling with smaller SR Ca2+ store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca2+ reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca2+ dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca2+ cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca2+ dynamics is unstable and Ca2+ waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level. PMID:23056145

  10. The multifactorial role of the 3Rs in shifting the harm-benefit analysis in animal models of disease

    PubMed Central

    Graham, Melanie L.; Prescott, Mark J.

    2015-01-01

    Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit is much more evident in translational research aimed at developing treatments for direct application in humans or animals suffering from disease. Though benefit may be easier to define, it should certainly not be considered automatic. Issues related to model validity seriously compromise experiments and have been implicated as a major impediment in translation, especially in complex disease models where harms to animals can be intensified. Increased investment and activity in the 3Rs is delivering new research models, tools and approaches with reduced reliance on animal use, improved animal welfare, and improved scientific and predictive value. PMID:25823812

  11. Targeting of Androgen Receptor Expression by Andro-miRs as Novel Adjunctive Therapeutics in Prostate Cancer.

    PubMed

    Ebron, Jey Sabith; Weyman, Crystal M; Shukla, Girish C

    2013-04-01

    Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant prostate cancer (CRPC). The monoallelic Androgen Receptor (AR) is associated with the onset, growth and development of Prostate cancer. The AR is a ligand-dependent transcription factor, and the targeting of androgen- and AR-signaling axis remains the primary therapeutic option for Prostate cancer (PCa) treatment. A durable and functional disruption of AR signaling pathways combining both traditional and novel therapeutics is likely to provide better treatment options for CRPC. Recent work has indicated that expression of AR is modulated at the posttranscriptional level by regulatory miRNAs. Due to a relatively long 3' untranslated region (UTR) of AR mRNA, the posttranscription expression is likely to be regulated by hundreds of miRNAs in normal as well as in disease state. The main objective of the article is to offer a thought-provoking concept of "andro-miRs" and their potential application in AR gene expression targeting. This new paradigm for targeting constitutively active AR and its tumor specific splicing isoforms using andro-miRs may pave the way for a novel adjunctive therapy and improved treatment of CRPC.

  12. CYP3A4 intronic SNP rs35599367 (CYP3A4*22) alters RNA splicing.

    PubMed

    Wang, Danxin; Sadee, Wolfgang

    2016-01-01

    Cytochrome P450 3A4 (CYP3A4) metabolizes 30-50% of clinically used drugs. Large interperson variability in CYP3A4 activity affects response to CYP3A4 substrate drugs. We had demonstrated that an intronic single nucleotide polymorphism rs35599367 (CYP3A4*22, located in intron 6) reduces mRNA/protein expression; however, the underlying mechanism remained unknown. Here we show that CYP3A4*22 is associated with a two-fold or greater increase in formation of a nonfunctional CYP3A4 alternative splice variant with partial intron 6 retention in human liver (P=0.006), but not in small intestines. Consistent with this observation, in-vitro transfection experiments with a CYP3A4 minigene (spanning from intron 5 to intron 7) demonstrated that plasmids carrying the rs35599367 minor T allele caused significantly greater intron 6 retention than the C allele in liver derived HepG2 cells, but not in intestine-derived LS-174T cells. These results indicate that tissue-specific increased formation of nonfunctional alternative splice variant causes reduced CYP3A4 mRNA/protein expression in CYP3A4*22 carriers.

  13. RS-25 for the NASA Crew Launch Vehicle: The Evolution of SSME for Space Exploration

    NASA Technical Reports Server (NTRS)

    Kynard, Michael H.; Genge, Gary G.; Greene, William D.; Jacobs, William; McArthur, J. Craig; Mims, Michael J.; Tepool, J. Eric; Wofford, Steven J.

    2006-01-01

    As a first step towards the fulfillment of the National Vision for Space Exploration, NASA has begun development of the Crew Launch Vehicle (CLV). The CLV will act, in conjunction with the Crew Exploration Vehicle, as the next generation human launch system to first support missions to the International Space Station (ISS), then later to support the lunar return missions, and then after that to exploration missions to Mars and beyond. The CLV is a two-stage launch vehicle with the first stage based upon the Space Shuttle solid rocket booster. The newly designed, expendable second stage is powered by a single RS-25 liquid hydrogen/liquid oxygen rocket engine. The RS-25 is essentially the Space Shuttle Main Engine (SSME) evolved for a new mission, new environments, and new conditions. The CLV Upper-Stage Engine (USE) office has been established to develop the RS-25 in support of the CLV Project. This paper presents an outline and discussion of the risks associated with this endeavor of transforming the SSME into the upper-stage, altitude-start RS-25 and the plans being undertaken to understand and mitigate these risks. In addition, to meet the long-term requirements of the CLV launch manifest, it will be necessary to redevelop the RS-25, with its long history as the reusable SSME for the Space Shuttle Program, as an expendable engine. While the first flights of CLV will be using heritage SSME hardware, beyond that a new version of RS-25 as an expendable engine is being pursued by the CLV USE element. The goals of this work include the need to make the hardware more producible while maintaining the inherent and inherited reliability of the basic design. This paper will also discuss the risks and present the plans for developing both this next generation version of the RS-25 and for developing the manufacturing capacity necessary to support the CLV Project.

  14. Biocompatibility of rapidly solidified magnesium alloy RS66 as a temporary biodegradable metal.

    PubMed

    Willbold, Elmar; Kalla, Katharina; Bartsch, Ivonne; Bobe, Katharina; Brauneis, Maria; Remennik, Sergei; Shechtman, Dan; Nellesen, Jens; Tillmann, Wolfgang; Vogt, Carla; Witte, Frank

    2013-11-01

    Biodegradable magnesium-based alloys are very promising materials for temporary implants. However, the clinical use of magnesium-based alloys is often limited by rapid corrosion and by insufficient mechanical stability. Here we investigated RS66, a magnesium-based alloy with extraordinary physicochemical properties of high tensile strength combined with a high ductility and a homogeneous grain size of ~1 μm which was obtained by rapid solidification processing and reciprocal extrusion. Using a series of in vitro and in vivo experiments, we analyzed the biodegradation behavior and the biocompatibility of this alloy. In vitro, RS66 had no cytotoxic effects in physiological concentrations on the viability and the proliferation of primary human osteoblasts. In vivo, RS66 cylinders were implanted into femur condyles, under the skin and in the muscle of adult rabbits and were monitored for 1, 2, 3, 4 and 8 weeks. After explantation, the RS66 cylinders were first analyzed by microtomography to determine the remaining RS66 alloy and calculate the corrosion rates. Then, the implantation sites were examined histologically for healing processes and foreign body reactions. We found that RS66 was corroded fastest subcutaneously followed by intramuscular and bony implantation of the samples. No clinical harm with transient gas cavities during the first 6 weeks in subcutaneous and intramuscular implantation sites was observed. No gas cavities were formed around the implantation site in bone. The corrosion rates in the different anatomical locations correlated well with the local blood flow prior to implantation. A normal foreign body reaction occurred in all tissues. Interestingly, no enhanced bone formation could be observed around the corroding samples in the condyles. These data show that RS66 is biocompatible, and due to its interesting physicochemical properties, this magnesium alloy is a promising material for biodegradable implants.

  15. Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer

    PubMed Central

    Ou, Jingxing; Vijayasarathy, Camasamudram; Ziccardi, Lucia; Chen, Shan; Zeng, Yong; Marangoni, Dario; Pope, Jodie G.; Bush, Ronald A.; Wu, Zhijian; Li, Wei; Sieving, Paul A.

    2015-01-01

    Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor–depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1–signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology. PMID:26098217

  16. Research on texture feature of RS image based on cloud model

    NASA Astrophysics Data System (ADS)

    Wang, Zuocheng; Xue, Lixia

    2008-10-01

    This paper presents a new method applied to texture feature representation in RS image based on cloud model. Aiming at the fuzziness and randomness of RS image, we introduce the cloud theory into RS image processing in a creative way. The digital characteristics of clouds well integrate the fuzziness and randomness of linguistic terms in a unified way and map the quantitative and qualitative concepts. We adopt texture multi-dimensions cloud to accomplish vagueness and randomness handling of texture feature in RS image. The method has two steps: 1) Correlativity analyzing of texture statistical parameters in Grey Level Co-occurrence Matrix (GLCM) and parameters fuzzification. GLCM can be used to representing the texture feature in many aspects perfectly. According to the expressive force of texture statistical parameters and by Correlativity analyzing of texture statistical parameters, we can abstract a few texture statistical parameters that can best represent the texture feature. By the fuzziness algorithm, the texture statistical parameters can be mapped to fuzzy cloud space. 2) Texture multi-dimensions cloud model constructing. Based on the abstracted texture statistical parameters and fuzziness cloud space, texture multi-dimensions cloud model can be constructed in micro-windows of image. According to the membership of texture statistical parameters, we can achieve the samples of cloud-drop. By backward cloud generator, the digital characteristics of texture multi-dimensions cloud model can be achieved and the Mathematical Expected Hyper Surface(MEHS) of multi-dimensions cloud of micro-windows can be constructed. At last, the weighted sum of the 3 digital characteristics of micro-window cloud model was proposed and used in texture representing in RS image. The method we develop is demonstrated by applying it to texture representing in many RS images, various performance studies testify that the method is both efficient and effective. It enriches the cloud

  17. The 8q24 rs6983267G variant is associated with increased thyroid cancer risk.

    PubMed

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Polanco Echeverry, Guadalupe; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carmona, Luis G Carvajal

    2015-10-01

    The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11-1.27, P=4.03×10(-7)), Japan (OR=1.20, 95% CI: 1.03-1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99-1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10(-7), OR=1.13, 95% CI: 1.08-1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%.

  18. 8q24 rs6983267G variant is associated with increased thyroid cancer risk

    PubMed Central

    Sahasrabudhe, Ruta; Estrada, Ana; Lott, Paul; Martin, Lynn; Echeverry, Guadalupe Polanco; Velez, Alejandro; Neta, Gila; Takahasi, Meiko; Saenko, Vladimir; Mitsutake, Norisato; Jaeguer, Emma; Duque, Carlos Simon; Rios, Alejandro; Bohorquez, Mabel; Prieto, Rodrigo; Criollo, Angel; Echeverry, Magdalena; Tomlinson, Ian; Carvajal Carmona, Luis G.

    2015-01-01

    The G allele of the rs6983267 single nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in thyroid cancer susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3,067 cases and 8,575 controls. We detected significant associations between rs6983267G and thyroid cancer in the British Isles (Odds Ratio, OR= 1.19, 95% confidence interval, CI: 1.11–1.27, P= 4.03 × 10−7), Japan (OR= 1.20, 95% CI: 1.03–1.41, P= 0.022) and a borderline significant association of similar effect direction and size in Colombia (OR= 1.19, 95% CI: 0.99–1.44, P= 0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5,484 cases and 12,594 controls, confirmed the association between rs6983267G and thyroid cancer (P= 1.23 × 10−7, OR= 1.13, 95% CI: 1.07–1.18). Our results therefore support the notion that rs6983267G is a bona fide thyroid cancer risk variant that increases the risk of disease by ~13%. PMID:26290501

  19. Basigin rs8259 Polymorphism Confers Decreased Risk of Chronic Heart Failure in a Chinese Population

    PubMed Central

    Li, Mu-Peng; Hu, Xiao-Lei; Yang, Yong-Long; Zhang, Yan-Jiao; Zhou, Ji-Peng; Peng, Li-Ming; Tang, Jie; Chen, Xiao-Ping

    2017-01-01

    Left ventricular remodeling is an essential risk factor contributing to the pathogenesis of chronic heart failure (CHF). Basigin (BSG) promotes cardiovascular inflammation and myocardial remodeling processes by induction of extracellular matrix metalloproteinases and inflammatory cytokines. BSG rs8259 polymorphism was associated with BSG expression and risk of acute coronary syndrome. Therefore, we investigated whether rs8259 polymorphism contributes to risk and prognosis of CHF in Chinese patients. In total 922 adult patients with CHF and 1107 matched healthy controls were enrolled. BSG rs8259 polymorphism was genotyped using PCR-restriction fragment length polymorphism. Whole blood BSG mRNA expression data from Genotype-Tissue Expression project was accessed. Evaluation of follow-up data was performed in only 15.2% (140) of the patients with CHF. BSG rs8259 TT genotype was associated with a decreased risk of CHF (OR = 0.83, 95% CI = 0.72–0.96, p = 0.010), especially in patients with hypertension (OR = 0.80, 95% CI = 0.68–0.95, p = 0.011) and coronary heart disease (OR = 0.81, 95% CI = 0.69–0.96, p = 0.013) after adjustment for multiple cardiovascular risk factors. Rs8259 T allele was associated with decreased BSG mRNA in whole blood from 338 healthy normal donors (p = 1.31 × 10−6). However, rs8259 polymorphism failed to exhibit an association with cardiovascular mortality (p = 0.283). BSG rs8259 polymorphism may contribute to decreased risk of CHF in a Chinese Han population. PMID:28230811

  20. Navy Force Structure and Shipbuilding Plans: Background and Issues for Congress

    DTIC Science & Technology

    2014-08-01

    reformulated for FY2016 and subsequent years to include the roughly $7.0 billion in additional funding that would be needed over the FYDP to fund the CVN... reformulated to include the $7 billion in additional funding needed to keep CVN-73 and its associated air wing, what other defense programs would have...including funding levels, legislative provisions, and report language ) can be found in the following CRS reports: • CRS Report RS20643, Navy Ford (CVN-78

  1. Genetic variants in PARP1 (rs3219090) and IRF4 (rs12203592) genes associated with melanoma susceptibility in a Spanish population

    PubMed Central

    2013-01-01

    Background Few high penetrance genes are known in Malignant Melanoma (MM), however, the involvement of low-penetrance genes such as MC1R, OCA2, ASIP, SLC45A2 and TYR has been observed. Lately, genome-wide association studies (GWAS) have been the ideal strategy to identify new common, low-penetrance susceptibility loci. In this case–control study, we try to validate in our population nine melanoma associated markers selected from published GWAS in melanoma predisposition. Methods We genotyped the 9 markers corresponding to 8 genes (PARP1, MX2, ATM, CCND1, NADSYN1, CASP8, IRF4 and CYP2R1) in 566 cases and 347 controls from a Spanish population using KASPar probes. Genotypes were analyzed by logistic regression and adjusted by phenotypic characteristics. Results We confirm the protective role in MM of the rs3219090 located on the PARP1 gene (p-value 0.027). Additionally, this SNP was also associated with eye color (p-value 0.002). A second polymorphism, rs12203592, located on the IRF4 gene was associated with protection to develop MM for the dominant model (p-value 0.037). We have also observed an association of this SNP with both lentigines (p-value 0.014) and light eye color (p-value 3.76 × 10-4). Furthermore, we detected a novel association with rs1485993, located on the CCND1 gene, and dark eye color (p-value 4.96 × 10-4). Finally, rs1801516, located on the ATM gene, showed a trend towards a protective role in MM similar to the one firstly described in a GWAS study. Conclusions To our knowledge, this is the first time that these SNPs have been associated with MM in a Spanish population. We confirmed the proposed role of rs3219090, located on the PARP1 gene, and rs12203592, located on the IRF4 gene, as protective to MM along the same lines as have previous genome-wide associated works. Finally, we have seen associations between IRF4, PARP1, and CCND1 and phenotypic characteristics, confirming previous results for the IRF4 gene and presenting novel data

  2. Association of methionine synthase rs1801394 and methionine synthase reductase rs1805087 polymorphisms with meningioma in adults: A meta-analysis

    PubMed Central

    ZENG, XIAN-TAO; LU, JUN-TI; TANG, XIANG-JUN; WENG, HONG; LUO, JIE

    2014-01-01

    Several epidemiological studies suggested that methionine synthase (MTRR) rs1801394 and methionine synthase reductase (MTR) rs1805087 polymorphisms may be involved in the risk of meningioma in adults; however, the results from different case-control studies have been inconsistent. Therefore, we performed a meta-analysis to investigate the association of MTRR and MTR polymorphisms with meningioma. PubMed, Web of Knowledge, China National Knowledge Infrastructure and Wanfang databases were searched up to October 30, 2013 and 3 publications, involving 7 case-control studies, were finally included. Following data extraction, a meta-analysis was conducted using Stata 12.0 software. The pooled results based on the fixed effects model demonstrated that the MTRR rs1801394 polymorphism was associated with an increased risk of meningioma [odds ratio (OR)=1.18, 95% confidence interval (CI): 1.05–1.32 for G vs. A; OR=1.41, 95% CI: 1.12–1.77 for GG vs. AA; OR=1.08, 95% CI: 0.94–1.33 for AG vs. AA; OR=1.19, 95% CI: 1.01–1.40 for (AG+GG) vs. AA; and OR=1.32, 95% CI: 1.07–1.63 for GG vs. (AG+AA)]; however, an association between the MTR rs1805087 polymorphism and the risk of meningioma was not identified [OR=0.99, 95% CI: 0.88–1.12 for G vs. A; OR=1.09, 95% CI: 0.80–1.48 for GG vs. AA; OR=0.95, 95% CI: 0.82–1.11 for AG vs. AA; OR=0.97, 95% CI: 0.84–1.13 for (AG+GG) vs. AA; and OR=1.09, 95% CI: 0.80–1.48 for GG vs. (AG+AA)]. Therefore, the currently available evidence suggests that the MTRR rs1801394 polymorphism may increase the risk of meningioma, whereas the MTRR rs1801394 polymorphism is not associated with meningioma. PMID:24748989

  3. Effects of PSCA rs2294008 (C/T) and c-MYC rs9642880 (G/T) polymorphisms on bladder cancer: evidence from a meta-analysis

    PubMed Central

    Gao, Jie; Yang, Peng-Tao; Diao, Yan; Kang, Hua-Feng; Zhao, Yang; Lin, Shuai; Wang, Zi-Ming; Wang, Meng; Wang, Xi-Jing; Dai, Zhi-Jun

    2015-01-01

    Previous studies have investigated the associations between the two polymorphisms (prostate stem cell antigen (PSCA) rs2294008 C/T and c-MYC rs9642880 G/T) and bladder cancer (BC) risk. However, the results are inconsistent. We therefore carried out a meta-analysis to estimate the relationship between PSCA/c-MYC polymorphisms and BC risk. We searched PubMed up to November 2014 to identify potentially eligible literatures. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations, the data were further stratified by ethnicity. Heterogeneity was evaluated by Q test and I2 statistics. Begg’s funnel plot and Egger’s test were used to assess the publication bias. 11 studies from 9 articles were identified, including a total of 16,814 cancer cases and 52,868 case-free controls. We found a significant association between PSCA rs2294008 polymorphism and BC risk (the allele contrast model: OR = 1.14, 95% CI = 1.11-1.18; homozygote comparison: OR = 1.28, 95% CI = 1.20-1.37; heterozygote comparison: OR = 1.23, 95% CI = 1.17-1.30; dominant model: OR = 1.25, 95% CI = 1.19-1.31 and recessive model: OR = 1.13, 95% CI = 1.07-1.20). Moreover, a significant increased risk of BC was confirmed both in Caucasian and in Asians. For c-MYC rs9642880 polymorphism, significant increased BC risk was detected under the following genetic models (the allele contrast model: OR = 1.20, 95% CI = 1.13-1.27; homozygote comparison: OR = 1.37, 95% CI = 1.21-1.55; heterozygote comparison: OR = 1.20, 95% CI = 1.09-1.32; dominant model: OR = 1.25, 95% CI = 1.14-1.37 and recessive model: OR = 1.26, 95% CI = 1.13-1.40). Further stratified analysis by ethnicity also observed the same results. This meta-analysis suggested that PSCA rs2294008 and c-MYC rs9642880 polymorphisms may increase the BC risk. Further studies are needed to clarify the effects. PMID:25932146

  4. The CYP7A1 gene rs3808607 variant is associated with susceptibility of tuberculosis in Moroccan population

    PubMed Central

    Qrafli, Mounia; Amar, Youssef; Bourkadi, Jamaleddine; Ben Amor, Jouda; Iraki, Ghali; Bakri, Youssef; Amzazi, Saaîd; Lahlou, Ouafae; Seghrouchni, Fouad; El Aouad, Rajae; Sadki, Khalid

    2014-01-01

    Introduction Despite the medical progress in treatment. Tuberculosis (TB) continues to be a serious global health problem. A genome-wide linkage study identified a major susceptibility locus on chromosomal region 8q12-q13 in Moroccan TB patients. The CYP7A1 gene is located in this region and codes for cholesterol 7a-hydroxylase, an enzyme involved in cholesterol catabolism. Methods We selected three SNPs (rs3808607, rs8192875 and rs8192879) and studied their genotype and allele frequencies distribution in patients with pulmonary (PTB) or pleural TB (pTB), and compared them to Healthy Controls (HC). Genotyping of rs8192875 and rs8192879 SNPs was carried out using the Taq Man SNP genotyping Assay while rs3808607 was investigated by PCR-RFLP. Results We reported here for the first time a statistically significant increase in the AA homozygote genotype frequency of rs3808607 in PTB patients compared to HC (p = 0.02, OR = 1.93, 95% CI: 1.93 (1.07;3.49). The increased risk of developing TB was maintained when we combined the groups of patients (PTB-pTB) (p = 0.01, OR= 1.91, 95% CI = (1.07 - 3.42). In contrast, no genetic association was observed between the rs8192875 or rs8192879 polymorphisms and TB. Conclusion Our investigations suggest that rs3808607 may play a role in susceptibility to TB in a Moroccan population. PMID:25360185

  5. DeAnnIso: a tool for online detection and annotation of isomiRs from small RNA sequencing data

    PubMed Central

    Zhang, Yuanwei; Zang, Qiguang; Zhang, Huan; Ban, Rongjun; Yang, Yifan; Iqbal, Furhan; Li, Ao; Shi, Qinghua

    2016-01-01

    Small RNA (sRNA) Sequencing technology has revealed that microRNAs (miRNAs) are capable of exhibiting frequent variations from their canonical sequences, generating multiple variants: the isoforms of miRNAs (isomiRs). However, integrated tool to precisely detect and systematically annotate isomiRs from sRNA sequencing data is still in great demand. Here, we present an online tool, DeAnnIso (Detection and Annotation of IsomiRs from sRNA sequencing data). DeAnnIso can detect all the isomiRs in an uploaded sample, and can extract the differentially expressing isomiRs from paired or multiple samples. Once the isomiRs detection is accomplished, detailed annotation information, including isomiRs expression, isomiRs classification, SNPs in miRNAs and tissue specific isomiR expression are provided to users. Furthermore, DeAnnIso provides a comprehensive module of target analysis and enrichment analysis for the selected isomiRs. Taken together, DeAnnIso is convenient for users to screen for isomiRs of their interest and useful for further functional studies. The server is implemented in PHP + Perl + R and available to all users for free at: http://mcg.ustc.edu.cn/bsc/deanniso/ and http://mcg2.ustc.edu.cn/bsc/deanniso/. PMID:27179030

  6. IPMDS-Sponsored Scale Translation Program: Process, Format, and Clinimetric Testing Plan for the MDS-UPDRS and UDysRS.

    PubMed

    Goetz, Christopher G; Stebbins, Glenn T; Wang, Lu; LaPelle, Nancy R; Luo, Sheng; Tilley, Barbara C

    2014-06-01

    We present the methodology and results of the clinimetric testing program for non-English translations of International Parkinson and Movement Disorder Society (MDS)-sponsored scales. The programs focus on the MDS revision of the UPDRS (MDS-UPDRS) and the Unified Dyskinesia Rating Scale (UDysRS). The original development teams of both the MDS-UPDRS and UDysRS envisioned official non-English translations and instituted a rigorous translation methodology. The formal process includes five core steps: (1) registration and start-up; (2) translation and independent back-translation; (3) cognitive pretesting to establish that the translation is clear and that it is comfortably administered to and completed by native-speaker raters and patients; (4) field testing in the native language using a large sample of Parkinson's disease patients; and (5) full clinimetric testing. To date, the MDS-UPDRS has 21 active language programs. Nine official translations are available, having completed all phases successfully, and the others are in different stages of development. For the UDysRS, 19 programs are active, with three official translations now available and the rest in development at different stages. Very few scales in neurology and none in movement disorders have fully validated translations, and this model may be adopted or modified by other scale programs to allow careful validation of translations. Having validated translations allows for maximal homogeneity of tools utilized in multicenter research or clinical trial programs.

  7. Prediction of solubilities for ginger bioactive compounds in hot water by the COSMO-RS method

    NASA Astrophysics Data System (ADS)

    Zaimah Syed Jaapar, Syaripah; Azian Morad, Noor; Iwai, Yoshio

    2013-04-01

    The solubilities in water of four main ginger bioactives, 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol, were predicted using a conductor-like screening model for real solvent (COSMO-RS) calculations. This study was conducted since no experimental data are available for ginger bioactive solubilities in hot water. The σ-profiles of these selected molecules were calculated using Gaussian software and the solubilities were calculated using the COSMO-RS method. The solubilities of these ginger bioactives were calculated at 50 to 200 °C. In order to validate the accuracy of the COSMO-RS method, the solubilities of five hydrocarbon molecules were calculated using the COSMO-RS method and compared with the experimental data in the literature. The selected hydrocarbon molecules were 3-pentanone, 1-hexanol, benzene, 3-methylphenol and 2-hydroxy-5-methylbenzaldehyde. The calculated results of the hydrocarbon molecules are in good agreement with the data in the literature. These results confirm that the solubilities of ginger bioactives can be predicted using the COSMO-RS method. The solubilities of the ginger bioactives are lower than 0.0001 at temperatures lower than 130 °C. At 130 to 200 °C, the solubilities increase dramatically with the highest being 6-shogaol, which is 0.00037 mole fraction, and the lowest is 10-gingerol, which is 0.000039 mole fraction at 200 °C.

  8. Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population.

    PubMed

    Mačeková, Soňa; Bernasovský, Ivan; Gabriková, Dana; Bôžiková, Alexandra; Bernasovská, Jarmila; Boroňová, Iveta; Behulová, Regina; Svíčková, Petra; Petrejčíková, Eva; Soták, Miroslav; Sovičová, Adriana; Carnogurská, Jana

    2012-01-01

    The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.

  9. CLU rs2279590 polymorphism contributes to Alzheimer's disease susceptibility in Caucasian and Asian populations.

    PubMed

    Zhang, Shuyan; Zhang, Donghui; Jiang, Yongshuai; Wu, Lina; Shang, Hong; Liu, Jiafeng; Feng, Rennan; Liao, Mingzhi; Zhang, Liangcai; Liu, Yong; Liu, Guiyou; Li, Keshen

    2015-03-01

    It is reported that CLU rs2279590 polymorphism is significantly associated with Alzheimer's disease (AD) in European ancestry. Recent studies investigated rs2279590 polymorphism in Asian population (Chinese, Japanese and Korean). Four studies showed negative association and two studies showed weak association between rs2279590 and AD. We believe that the weak association or no association may be caused by the relatively small sample size in Asian population. Here, we reinvestigated the association in Asian population. Meanwhile, to investigate the genetic heterogeneity of the rs2279590 polymorphism in Asian and Caucasian populations, we searched the PubMed and AlzGene databases and selected 11 independent studies (6 studies in Asian population and 5 studies in Caucasian population) including 20,655 individuals (8,605 cases and 12,050 controls) for meta-analysis. Our results showed significant association between rs2279590 polymorphism and AD in Asian population with P = 2.00E-04 and P = 2.00E-04 using additive and recessive models, respectively. We observed no significant heterogeneity between Asian and Caucasian populations. We believe that our results may be helpful to understand the mechanisms of CLU in AD pathogenesis and will be useful for future genetic studies in AD.

  10. The TP53 gene rs1042522 C>G polymorphism and neuroblastoma risk in Chinese children.

    PubMed

    He, Jing; Wang, Fenghua; Zhu, Jinhong; Zhang, Zhuorong; Zou, Yan; Zhang, Ruizhong; Yang, Tianyou; Xia, Huimin

    2017-03-08

    TP53, a tumor suppressor gene, plays a critical role in cell cycle control, apoptosis, and DNA damage repair. Previous studies have indicated that the TP53 gene Arg72Pro (rs1042522 C>G) polymorphism is associated with susceptibility to various types of cancer. We evaluated the association of the TP53 gene rs1042522 C>G polymorphism with neuroblastoma susceptibility in a hospital-based study among the Chinese Han population. Enrolled were 256 patients and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) generated using logistic regression models were used to determine the strength of the association of interest. No association was detected between rs1042522 C>G polymorphism and neuroblastoma risk. In our stratification analysis of age, gender, sites of origin, and clinical stages, we observed that subjects with rs1042522 CG/GG genotypes had a lower risk of developing neuroblastoma in the mediastinum (Adjusted OR=0.52, 95% CI=0.33-0.82, P=0.005) than those carrying the CC genotype. These results indicate that TP53 gene rs1042522 C>G polymorphism may exert a weak and site-specific effect on neuroblastoma risk in Southern Chinese children and warrant further confirmation.

  11. FIRE, A Test Bed for ARIES-RS/AT Advanced Physics and Plasma Technology

    SciTech Connect

    Dale M. Meade

    2004-10-21

    The overall vision for FIRE [Fusion Ignition Research Experiment] is to develop and test the fusion plasma physics and plasma technologies needed to realize capabilities of the ARIES-RS/AT power plant designs. The mission of FIRE is to attain, explore, understand and optimize a fusion dominated plasma which would be satisfied by producing D-T [deuterium-tritium] fusion plasmas with nominal fusion gains {approx}10, self-driven currents of {approx}80%, fusion power {approx}150-300 MW, and pulse lengths up to 40 s. Achieving these goals will require the deployment of several key fusion technologies under conditions approaching those of ARIES-RS/AT. The FIRE plasma configuration with strong plasma shaping, a double null pumped divertor and all metal plasma-facing components is a 40% scale model of the ARIES-RS/AT plasma configuration. ''Steady-state'' advanced tokamak modes in FIRE with high beta, high bootstrap fraction, and 100% noninductive current drive are suitable for testing the physics of the ARIES-RS/A T operating modes. The development of techniques to handle power plant relevant exhaust power while maintaining low tritium inventory is a major objective for a burning plasma experiment. The FIRE high-confinement modes and AT-modes result in fusion power densities from 3-10 MWm{sup -3} and neutron wall loading from 2-4 MWm{sup -2} which are at the levels expected from the ARIES-RS/AT design studies.

  12. NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis

    PubMed Central

    2014-01-01

    Background A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population. Methods We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays. Results NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS. Conclusions Our results indicate that NQO1 rs1800566 does not have an effect on MS disease risk. PMID:24755231

  13. Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis

    PubMed Central

    Li, Jingguang; Zhao, Yajun; Li, Rena; Broster, Lucas S.; Zhou, Chenglin; Yang, Suyong

    2015-01-01

    A common variant in the oxytocin receptor gene (OXTR), rs53576, has been broadly linked to socially related personality traits and behaviors. However, the pattern of published results is inconsistent. Here, we performed a meta-analysis to comprehensively evaluate the association. The literature was searched for relevant studies and effect sizes between individuals homozygous for the G allele (GG) and individuals with A allele carriers (AA/AG). Specifically, two indices of sociality were evaluated independently: i) general sociality (24 samples, n = 4955), i.e., how an individual responds to other people in general; and ii) close relationships (15 samples, n = 5262), i.e., how an individual responds to individuals with closed connections (parent-child or romantic relationship). We found positive association between the rs53576 polymorphism and general sociality (Cohen’s d = 0.11, p = .02); G allele homozygotes had higher general sociality than the A allele carriers. However, the meta-analyses did not detect significant genetic association between rs53576 and close relationships (Cohen’s d = 0.01, p = .64). In conclusion, genetic variation in the rs53576 influences general sociality, which further implies that it is worthy to systematically examine whether the rs53576 is a valid genetic marker for socially related psychiatric disorders. PMID:26121678

  14. BOREAS RS-12 Automated Ground Sunphotometer Measurements in the SSA

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Lobitz, Brad; Spanner, Michael; Wrigley, Robert

    2000-01-01

    The BOREAS RSS-12 team collected both ground and airborne sunphotometer measurements for use in characterizing the aerosol optical properties of the atmosphere during the BOREAS data collection activities. These measurements are to be used to: 1) measure the magnitude and variability of the aerosol optical depth in both time and space; 2) determine the optical properties of the boreal aerosols; and 3) atmospherically correct some remotely sensed data acquired during BOREAS. These data cover selected days and times from May to September 1994 and were taken from one of two ground sites near Candle Lake in the SSA. The data described in this document are from the field sunphotometer data. The data are stored in tabular ASCII files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  15. Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation.

    PubMed

    Ghoussaini, Maya; French, Juliet D; Michailidou, Kyriaki; Nord, Silje; Beesley, Jonathan; Canisus, Sander; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Dicks, Ed; Milne, Roger L; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Alonso, M Rosario; Pita, Guillermo; Neuhausen, Susan L; Anton-Culver, Hoda; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Tessier, Daniel C; Vincent, Daniel; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Ito, Hidemi; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Wu, Anna H; Van Den Berg, David; Lambrechts, Diether; Floris, Giuseppe; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Haiman, Christopher A; Le Marchand, Loic; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Borresen-Dale, Anne-Lise; Zheng, Wei; Cai, Qiuyin; Winqvist, Robert; Pylkäs, Katri; Andrulis, Irene L; Devilee, Peter; Tollenaar, Rob A E M; García-Closas, Montserrat; Figueroa, Jonine; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hooning, Maartje J; Koppert, Linetta B; Li, Jingmei; Shu, Xiao-Ou; Zheng, Ying; Cox, Angela; Cross, Simon S; Shah, Mitul; Rhenius, Valerie; Choi, Ji-Yeob; Kang, Daehee; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Luccarini, Craig; Conroy, Don M; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Olswold, Curtis; Slager, Susan; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Schoemaker, Minouk J; Simard, Jacques; Pharoah, Paul D P; Kristensen, Vessela; Chenevix-Trench, Georgia; Easton, Douglas F; Dunning, Alison M; Edwards, Stacey L

    2016-10-06

    Genome-wide association studies (GWASs) have revealed increased breast cancer risk associated with multiple genetic variants at 5p12. Here, we report the fine mapping of this locus using data from 104,660 subjects from 50 case-control studies in the Breast Cancer Association Consortium (BCAC). With data for 3,365 genotyped and imputed SNPs across a 1 Mb region (positions 44,394,495-45,364,167; NCBI build 37), we found evidence for at least three independent signals: the strongest signal, consisting of a single SNP rs10941679, was associated with risk of estrogen-receptor-positive (ER(+)) breast cancer (per-g allele OR ER(+) = 1.15; 95% CI 1.13-1.18; p = 8.35 × 10(-30)). After adjustment for rs10941679, we detected signal 2, consisting of 38 SNPs more strongly associated with ER-negative (ER(-)) breast cancer (lead SNP rs6864776: per-a allele OR ER(-) = 1.10; 95% CI 1.05-1.14; p conditional = 1.44 × 10(-12)), and a single signal 3 SNP (rs200229088: per-t allele OR ER(+) = 1.12; 95% CI 1.09-1.15; p conditional = 1.12 × 10(-05)). Expression quantitative trait locus analysis in normal breast tissues and breast tumors showed that the g (risk) allele of rs10941679 was associated with increased expression of FGF10 and MRPS30. Functional assays demonstrated that SNP rs10941679 maps to an enhancer element that physically interacts with the FGF10 and MRPS30 promoter regions in breast cancer cell lines. FGF10 is an oncogene that binds to FGFR2 and is overexpressed in ∼10% of human breast cancers, whereas MRPS30 plays a key role in apoptosis. These data suggest that the strongest signal of association at 5p12 is mediated through coordinated activation of FGF10 and MRPS30, two candidate genes for breast cancer pathogenesis.

  16. An Xp22.1-p22.2 YAC contig encompassing the disease loci for RS, KFSD, CLS, HYP and RP15: refined localization of RS.

    PubMed

    Van de Vosse, E; Bergen, A A; Meershoek, E J; Oosterwijk, J C; Gregory, S; Bakker, B; Weissenbach, J; Coffey, A J; van Ommen, G J; Den Dunnen, J T

    1996-01-01

    To facilitate the positional cloning of the genes involved in retinoschisis (RS), keratosis follicularis spinulosa decalvans (KFSD), Coffin-Lowry syndrome (CLS), X-linked hypophosphatemic rickets (XLH, locus name HYP) and X-linked dominant cone-rod degeneration (locus name RP15), we have extended the molecular map of the Xp22 region. Screening of several YAC libraries allowed us to identify 156 YACs, 52 of which localize between markers DXS414 (P90) and DXS451 (kQST80H1). Analysis of their marker content facilitated the construction of a YAC contig from the region spanning (in this order): DXS414 - DXS987 - DXS207 - DXS1053 - DXS197 - DXS 43 - DXS1195 - DXS418 - DXS999 - PDHA1 - DXS7161 - DXS443 - DXS 7592 - DXS1229 - DXS365 - DXS7101 - DXS7593 - DXS1052 - DXS274 - DXS989 - DXS451. The region between DXS414 and DXS451 covers about 4.5-5 Mb. Two additional markers (DXS7593 and DXS7592) were placed in the region, thereby increasing the genetic resolution. Using the deduced marker order, the analysis of key recombinants in families segregating RS allowed us to refine the critical region for RS to 0.6 Mb, between DXS418 and DXS7161.

  17. The SaeRS Two-Component System of Staphylococcus aureus

    PubMed Central

    Liu, Qian; Yeo, Won-Sik; Bae, Taeok

    2016-01-01

    In the Gram-positive pathogenic bacterium Staphylococcus aureus, the SaeRS two-component system (TCS) plays a major role in controlling the production of over 20 virulence factors including hemolysins, leukocidins, superantigens, surface proteins, and proteases. The SaeRS TCS is composed of the sensor histidine kinase SaeS, response regulator SaeR, and two auxiliary proteins SaeP and SaeQ. Since its discovery in 1994, the sae locus has been studied extensively, and its contributions to staphylococcal virulence and pathogenesis have been well documented and understood; however, the molecular mechanism by which the SaeRS TCS receives and processes cognate signals is not. In this article, therefore, we review the literature focusing on the signaling mechanism and its interaction with other global regulators. PMID:27706107

  18. Polymorphism of MDM2 promoter 309 (rs 2279744) and the risk of PCOS.

    PubMed

    Chan, Ying; Jiang, Hongguo; Yang, Xiaoling; Li, Dongya; Ma, Lan; Luo, Ying; Tang, Wenru

    2016-01-01

    This study aimed at evaluating possible association between MDM2 SNP309 polymorphism (rs 2279744) and polycystic ovary syndrome (PCOS). One hundred and twenty-five women with PCOS and two hundred and fifty women without PCOS were collected from the department of reproductive medicine of college hospital in this case-control study. Peripheral blood samples were collected from all participants and DNA was extracted, MDM2 SNP309 polymorphism (rs 2279744) was determined from the 125 cases and 250 controls. Women were grouped into PCOS (n = 125) group and control group (n = 250). Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the association between MDM2 SNP309 polymorphism (rs 2279744) and PCOS. The distribution of T allele was significant higher in PCOS cases than controls. MDM2 SNP 309 T allele is associated with PCOS.

  19. High-resolution optical spectroscopy of RS Ophiuchi during 2008-2009

    NASA Astrophysics Data System (ADS)

    Somero, A.; Hakala, P.; Wynn, G. A.

    2017-01-01

    RS Ophiuchi (RS Oph) is a symbiotic variable and a recurrent nova (RN). We have monitored it with the Nordic Optical Telescope and obtained 30 high-resolution (R = 46 000) optical spectra over one orbital cycle during quiescence. To our knowledge, this is the best-sampled high-resolution spectroscopic data set of RS Oph over one orbital period. We do not detect any direct signatures of an accretion disc such as double peaked emission lines, but many line profiles are complex consisting of superimposed emission and absorption components. We measure the spin of the red giant and conclude that it is tidally locked to the binary orbit. We observe Na I absorption features, probably arising from the circumbinary medium, that has been shaped by previous RN outbursts. We do not detect any intrinsic polarization in the optical wavelengths.

  20. Genomic characterization of Ralstonia solanacearum phage ϕRS138 of the family Siphoviridae.

    PubMed

    Van Truong Thi, Bich; Pham Khanh, Nguyen Huan; Namikawa, Ryuta; Miki, Kaito; Kondo, Akihiro; Dang Thi, Phuong Thao; Kamei, Kaeko

    2016-02-01

    ϕRS138, a bacteriophage of the family Siphoviridae that lyses Ralstonia solanacearum, was isolated. The genomic DNA of ϕRS138 was 41,941 bp long with a GC content of 65.1 % and contained 56 putative open reading frames. The ϕRS138 genome could be divided into three regions based on similarities to other genomes: (1) a region containing genes encoding a putative transcriptional regulator and an integrase, similar to the prophage genes in Ralstonia solanacearum K60-1; (2) a region encoding proteins related to structural modules and virion morphogenesis, similar to genes in the Pseudomonas phages of the family Siphoviridae; and (3) a region highly similar to the genomes of other Ralstonia solanacearum strains.

  1. Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Merlo, Sebastjan; Starčević, Jovana Nikolajević; Mankoč, Sara; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Zorc, Marjeta; Petrovič, Daniel

    2016-01-01

    Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM. PMID:26881237

  2. Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Merlo, Sebastjan; Starčević, Jovana Nikolajević; Mankoč, Sara; Šantl Letonja, Marija; Cokan Vujkovac, Andreja; Zorc, Marjeta; Petrovič, Daniel

    2016-01-01

    Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM.

  3. Association of GDF1 rs4808863 with fetal congenital heart defects: a case–control study

    PubMed Central

    Zhang, Juan; Wu, Qingqing; Wang, Li; Li, Xiaofei; Ma, Yuqing; Yao, Ling

    2015-01-01

    Background Congenital heart defects (CHDs) are the most common fetal defects and the most important cause of child mortality and morbidity. Objective To investigate the association between growth/differentiation factor 1 (GDF1) polymorphisms and fetal CHDs, by evaluating the association of GDF1 rs4808863 with fetal CHDs. Design A case–control study. Setting Beijing, China. Participants We selected 124 fetuses with a CHD and a normal karyotype and normal array-based comparative genomic hybridisation analysis and compared them with 124 normal fetuses matched for gestational age and sex. Fetuses with a CHD, from 20 to 32 weeks of gestation were included. Fetuses with any chromosomal abnormalities, and fetuses from multiple pregnancies and those carried by pregnant women with chronic diseases, were excluded from this research. DNA extraction and genotyping were carried out for all cases to investigate the genotype distributions of GDF1 rs4808863. Results A significant difference was noted for the CT phenotype of GDF1 rs4808863 between the controls and the fetuses with CHDs using homozygote and heterozygote comparisons. The minor allele (T allele) of GDF1 rs4808863 was associated with an increased risk of CHD (p<0.05). A statistically significant difference between controls and fetuses with CHDs was noted in a comparison with the mutation genotype CT+TT and wild-type genotype CC (p<0.05) using dominant modal analysis. After stratification analysis, the CT phenotype, the minor allele (T allele) and the mutation genotype CT+TT of the rs4808863 polymorphism were associated with atrioventricular septal defect (AVSD), left ventricular outflow tract obstruction (LVOTO) and left–right laterality defects (p<0.05). Conclusions Our results suggest that the GDF1 rs4808863 polymorphism contributes to an increased risk of fetal CHDs, especially the subtypes of AVSD, LVOTO and left–right laterality defects. PMID:26656983

  4. Analyzing large-scale samples highlights significant association between rs10411210 polymorphism and colorectal cancer.

    PubMed

    He, Dongfeng; Ma, Lihong; Feng, Rennan; Zhang, Liangcai; Jiang, Yongshuai; Zhang, Yanqiao; Liu, Guiyou

    2015-08-01

    Colorectal cancer (CRC) is the third most common form of cancer and the second leading cause of cancer-related death in the Western countries. In order to detect common CRC genetic variants, genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants. RHPN2 is located on 9q13.11, which encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. RHPN2 gene rs10411210 polymorphism was identified to be significantly associated with CRC in European ancestry. GWAS and candidate studies investigate whether rs10411210 polymorphism is associated with CRC risk in European, Asian and American populations. However, most studies reported no association. Evidence shows that RHPN2 rs10411210 variant may be a prognostic biomarker for patients with surgically resected CRC. Here we reevaluated this association using large-scale samples from 15 studies (131580 samples including 53564 CRC cases and 78016 controls) using meta-analysis method by searching the PubMed and Google Scholar databases. We did not identify significant heterogeneity among these 15 studies (P=0.4201 and I(2)=2.8%). Our results showed significant association between rs10411210 and CRC (P=9.17E-14, odds ratio (OR)=1.10, 95% confidence interval (CI) 1.07-1.13). In subgroup analysis, we found significant association between rs10411210 and CRC in European population with P=5.70E-09, OR=1.14, 95% CI 1.10-1.20 and Asian population with P=3.36E-07, OR=1.11, 95% CI 1.07-1.16, but not American population with P=0.0576, OR=1.05, 95% CI 1.00-1.09. Collectively, our analysis further highlights significant association between rs10411210 polymorphism and colorectal cancer.

  5. SHBG Gene Polymorphism (rs1799941) Associates with Metabolic Syndrome in Children and Adolescents

    PubMed Central

    White, Marquitta J.; Eren, Fatih; Agirbasli, Deniz; Williams, Scott M.; Agirbasli, Mehmet

    2015-01-01

    Background Metabolic syndrome (MetS) is a complex disorder characterized by coexistence of several cardiometabolic (CM) factors, i.e. hyperlipidemia, obesity, high blood pressure and insulin resistance. The presence of MetS is strongly associated with increased risk of cardiovascular disease (CVD). The syndrome was originally defined as an adult disorder, but MetS has become increasingly recognized in children and adolescents. Methods Genetic variants influence biological components common to the CM factors that comprise MetS. We investigated single locus associations between six single nucleotide polymorphisms (SNPs), previously shown to modulate lipid or sex hormone binding globulin (SHBG) levels, with MetS in a Turkish pediatric cohort (37 cases, 323 controls). Results Logistic regression analysis revealed a significant association between rs1799941, located in SHBG, and MetS (OR = 3.09, p-value = 0.006). The association with MetS remained after sequential adjustment for each CM factor included in the syndrome definition, indicating that the identified association is not being driven by any single trait. A relationship between rs1799941 and SHBG levels, was also discovered, but it was dependent on MetS status. In control subjects, the A allele of rs1799941 associated with a significant increase in SHBG levels (p = 0.012), while in cases there was no association between rs1799941 and SHBG levels (p = 0.963). Conclusions The significant association between rs1799941 and MetS in children is not contingent on any single CM trait. Additionally, the presence of MetS may abrogate effect of rs1799941 polymorphism on SHBG levels in children. PMID:25647406

  6. Association between Tourette Syndrome and the Dopamine D3 Receptor Gene Rs6280

    PubMed Central

    He, Fan; Zheng, Yi; Huang, Huan-Huan; Cheng, Yu-Hang; Wang, Chuan-Yue

    2015-01-01

    Background: Tourette syndrome (TS) is a complex, heterozygous genetic disorder. The number of molecular genetic studies have investigated several candidate genes, particularly those implicated in the dopamine system. The dopamine D3 receptor (DRD3) gene has been considered as a candidate gene in TS. There was not any report about the association study of TS and DRD3 gene in Han Chinese population. We combined a case–control genetic association analysis and nuclear pedigrees transmission disequilibrium test (TDT) analysis to investigate the association between DRD3 gene rs6280 single nucleotide polymorphisms (SNPs) and TS in a Han Chinese population. Methods: A total of 160 TS patients was diagnosed by the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The DRD3 gene rs6280 SNPs were genotyped by TaqMan SNP genotyping assay technique in all subjects. We used a case–control genetic association analysis to compare the difference in genotype and allele frequencies between 160 TS patients and 90 healthy controls. At the same time, we used TDT analysis to identify the DRD3 gene rs6280 transmission disequilibrium among 101 nuclear pedigrees. Results: The genotype and allele frequency of DRD3 gene rs6280 SNPs had no statistical difference between control group (90) and TS group (160) (χ2 = 3.647, P = 0.161; χ2 = 0.643, P = 0.423) using Chi-squared test. At the basis of the 101 nuclear pedigrees, TDT analysis showed no transmission disequilibrium of DRD3 gene rs6280 SNPs (χ2 = 0; P = 1). Conclusions: Our findings provide no evidence for an association between DRD3 gene rs6280 and TS in the Han Chinese population. PMID:25698199

  7. MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

    PubMed

    Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

    2016-01-01

    Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

  8. Sigma receptors [σRs]: biology in normal and diseased states

    PubMed Central

    Rousseaux, Colin G.; Greene, Stephanie F.

    2016-01-01

    Abstract This review compares the biological and physiological function of Sigma receptors [σRs] and their potential therapeutic roles. Sigma receptors are widespread in the central nervous system and across multiple peripheral tissues. σRs consist of sigma receptor one (σ1R) and sigma receptor two (σ2R) and are expressed in numerous regions of the brain. The sigma receptor was originally proposed as a subtype of opioid receptors and was suggested to contribute to the delusions and psychoses induced by benzomorphans such as SKF-10047 and pentazocine. Later studies confirmed that σRs are non-opioid receptors (not an µ opioid receptor) and play a more diverse role in intracellular signaling, apoptosis and metabolic regulation. σ1Rs are intracellular receptors acting as chaperone proteins that modulate Ca2+ signaling through the IP3 receptor. They dynamically translocate inside cells, hence are transmembrane proteins. The σ1R receptor, at the mitochondrial-associated endoplasmic reticulum membrane, is responsible for mitochondrial metabolic regulation and promotes mitochondrial energy depletion and apoptosis. Studies have demonstrated that they play a role as a modulator of ion channels (K+ channels; N-methyl-d-aspartate receptors [NMDAR]; inositol 1,3,5 triphosphate receptors) and regulate lipid transport and metabolism, neuritogenesis, cellular differentiation and myelination in the brain. σ1R modulation of Ca2+ release, modulation of cardiac myocyte contractility and may have links to G-proteins. It has been proposed that σ1Rs are intracellular signal transduction amplifiers. This review of the literature examines the mechanism of action of the σRs, their interaction with neurotransmitters, pharmacology, location and adverse effects mediated through them. PMID:26056947

  9. FTO at rs9939609, Food Responsiveness, Emotional Control and Symptoms of ADHD in Preschool Children

    PubMed Central

    Velders, Fleur P.; De Wit, Jolanda E.; Jansen, Pauline W.; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Tiemeier, Henning

    2012-01-01

    The FTO minor allele at rs9939609 has been associated with body mass index (BMI: weight (kg)/height (m)2) in children from 5 years onwards, food intake, and eating behaviour. The high expression of FTO in the brain suggests that this gene may also be associated with behavioural phenotypes, such as impulsivity and control. We examined the effect of the FTO minor allele (A) at rs9939609 on eating behaviour, impulsivity and control in young children, thus before the BMI effect becomes apparent. This study was embedded in the Generation R Study, a population-based cohort from fetal life onwards. 1,718 children of European descent were genotyped for FTO at rs9939609. With logistic regression assuming an additive genetic model, we examined the association between the FTO minor allele and eating behaviour, impulsivity and control in preschool children. There was no relation between FTO at rs9939609 and child BMI at this age. The A allele at rs9939609 was associated with increased food responsiveness (OR 1.21, p = 0.03). Also, children with the A allele were less likely to have symptoms of ADHD (OR 0.74, p = 0.01) and showed more emotional control (OR 0.64, p = 0.01) compared to children without the A allele. Our findings suggest that before the association between FTO and BMI becomes apparent, the FTO minor allele at rs9939609 leads to increased food responsiveness, a decreased risk for symptoms of ADHD and better emotional control. Future studies are needed to investigate whether these findings represent one single mechanism or reflect pleiotropic effects of FTO. PMID:23155456

  10. Prostate stem cell antigen variation rs2294008 associated with the risk of bladder cancer

    PubMed Central

    Li, Maomao; Yu, Xi; Cheng, Liangliang; Huang, Yi; Weng, Guobin

    2015-01-01

    Several studies reported Prostate stem cell antigen (PSCA) rs2294008 was susceptibly associated with bladder cancer (BC) risk. However, the results were not entirely consistent. The aim of this study was to investigate the association between rs2294008 and BC risk. Comprehensive meta-analysis was preformed to provide a more precise assessment of the association between rs2294008 and BC risk. Twenty five studies involving 14,244 BC patients and 53,963 controls were included in our meta-analysis. The crude odds ratios (ORs) and the 95% confidence intervals (95% CIs) were used to evaluate the strength of the association. Pooled results indicated that the PSCA variant rs2294008-T was significantly connected with an increased risk of BC (OR = 1.15, 95% CI = 1.12-1.18, P(z) < 0.0001). Moreover, stratified analyses showed that rs2294008 significantly increased BC risk in European (OR = 1.10, 95% CI = 1.05-1.15, P(z) < 0.0001), North American (OR = 1.18, 95% CI = 1.12-1.24, P(z) < 0.0001), and Asian (OR = 1.17, 95% CI = 1.13-1.22, P(z) < 0.0001). In conclusion, our meta-analysis demonstrated that the PSCA rs2294008 is a risk factor for BC in European, Asian and North American. Further large case-control studies are needed to assess the relationship in other populations. Biologically functional studies are needed to verify the molecular mechanisms in the pathogenesis of BC. PMID:26550251

  11. R&D of low activation ferritic steels for fusion in japanese universities*1

    NASA Astrophysics Data System (ADS)

    Kohyama, Akira; Kohno, Yutaka; Asakura, Kentaro; Kayano, Hideo

    1994-09-01

    Following the brief review of the R&D of low activation ferritic steels in Japanese universities, the status of 9Cr-2W type ferritic steels development is presented. The main emphasis is on mechanical property changes by fast neutron irradiation in FFTF. Bend test, tensile test, CVN test and in-reactor creep results are provided including some data about low activation ferritic steels with Cr variation from 2.25 to 12%. The 9Cr-2W ferritic steel, denoted as JLF-1, showed excellent mechanical properties under fast neutron irradiation as high as 60 dpa. As potential materials for DEMO and beyond, innovative oxide dispersion strengthened (ODS) quasi-amorphous low activation ferritic steels are introduced. The baseline properties, microstructural evolution under ion irradiation and the recent progress of new processes are provided.

  12. The three Rs of fire safety, emergency action, and fire prevention planning: promoting safety at the worksite.

    PubMed

    Thompson, Marcella R

    2003-04-01

    Fire safety is of paramount importance for everyone. In many workplaces, the occupational health nurse's scope of practice encompasses safety related activities. Included within this role is the responsibility for fire safety, emergency action, and fire prevention planning. The Three Rs of fire safety, emergency action, and fire prevention plans are rules, responsibilities, and resources. Myriad building and fire safety codes, regulations, and standards exist with which an employer must comply. An employer's responsibility for installing, testing, inspecting, and maintaining fire safety related equipment is extensive. Emergency action and fire prevention planning begins with conducting a detailed physical survey and preparing site maps. It includes making key policy decisions, writing procedures, and training employees in those procedures by practicing and executing site drills. The best resources available for emergency planning are the local fire department and the property insurer. Planning ahead means an efficient emergency response if disaster strikes. It saves lives, limits property damage, and preserves the environment.

  13. Validation of heart rate monitor Polar RS800 for heart rate variability analysis during exercise.

    PubMed

    Hernando, David; Garatachea, Nuria; Almeida, Rute; Casajús, Jose Antonio; Bailón, Raquel

    2016-09-27

    Heart rate variability (HRV) analysis during exercise is an interesting non-invasive tool to measure the cardiovascular response to the stress of exercise. Wearable heart rate monitors are a comfortable option to measure RR intervals while doing physical activities. It is necessary to evaluate the agreement between HRV parameters derived from the RR series recorded by wearable devices and those derived from an ECG during dynamic exercise of low to high intensity.23 male volunteers performed an exercise stress test on a cycle ergometer. Subjects wore a Polar RS800 device while ECG was also recorded simultaneously to extract the reference RR intervals. A time-frequency spectral analysis was performed to extract the instantaneous mean heart rate (HRM), and the power of low frequency (PLF) and high frequency (PHF) components, the latter centred on the respiratory frequency. Analysis was done in intervals of different exercise intensity based on oxygen consumption. Linear correlation, reliability and agreement were computed in each interval.The agreement between the RR series obtained from the Polar device and from the ECG is high throughout the whole test, although the shorter the RR is, the more differences there are. Both methods are interchangeable when analysing HRV at rest. At high exercise intensity, HRM and PLF still presented a high correlation (ρ>0.8) and excellent reliability and agreement indices (above 0.9). However, the PHF measurements from the Polar showed reliability and agreement coefficients around 0.5 or lower when the level of the exercise increases (for levels of O2 above 60%).

  14. rsEGFP2 enables fast RESOLFT nanoscopy of living cells

    PubMed Central

    Grotjohann, Tim; Testa, Ilaria; Reuss, Matthias; Brakemann, Tanja; Eggeling, Christian; Hell, Stefan W; Jakobs, Stefan

    2012-01-01

    The super-resolution microscopy called RESOLFT relying on fluorophore switching between longlived states, stands out by its coordinate-targeted sequential sample interrogation using low light levels. While RESOLFT has been shown to discern nanostructures in living cells, the reversibly photoswitchable green fluorescent protein (rsEGFP) employed in these experiments was switched rather slowly and recording lasted tens of minutes. We now report on the generation of rsEGFP2 providing faster switching and the use of this protein to demonstrate 25–250 times faster recordings. DOI: http://dx.doi.org/10.7554/eLife.00248.001 PMID:23330067

  15. E. coli RS2GFP Retention Mechanisms in Laboratory-Scale Fractured Rocks: A Statistical Model

    NASA Astrophysics Data System (ADS)

    Rodrigues, S. N.; Qu, J.; Dickson, S. E.

    2011-12-01

    With billions of gallons of groundwater being withdrawn every day in the US and Canada, it is imperative to understand the mechanisms which jeopardize this resource and the health of those who rely on it. Porous media aquifers have typically been considered to provide significant filtration of particulate matter (e.g. microorganisms), while the fractures in fractured rock aquifers and aquitards are considered to act as contaminant highways allowing a large fraction of pathogens to travel deep into an aquifer relatively quickly. Recent research results indicate that fractured rocks filter out more particulates than typically believed. The goal of the research presented here is to quantify the number of E. coli RS2GFP retained in a single, saturated, laboratory-scale fracture, and to relate the retention of E. coli RS2GFP to the aperture field characteristics and groundwater flow rate. To achieve this goal, physical experiments were conducted at the laboratory-scale to quantify the retention of E. coli RS2GFP through several single, saturated, dolomitic limestone fractures under a range of flow rates. These fractures were also cast with a transparent epoxy in order to visualize the transport mechanisms in the various different aperture fields. The E. coli RS2GFP is tagged with a green-fluorescent protein (GFP) that is used to obtain visualization data when excited by ultraviolet light. A series of experiments was conducted, each of which involved the release of a known number of E. coli RS2GFP at the upstream end of the fracture and measuring the effluent concentration profile. These experiments were conducted using both the natural rock and transparent cast of several different aperture fields, under a range of flow rates. The effects of different aperture field characteristics and flow rates on the retention of E. coli RS2GFP will be determined by conducting a statistical analysis of the retention data under different experimental conditions. The images captured

  16. Implementation of RS-485 Communication between PLC and PC of Distributed Control System Based on VB

    NASA Astrophysics Data System (ADS)

    Lian Zhang, Chuan; Da Huang, Zhi; Qing Zhou, Gui; Chong, Kil To

    2015-05-01

    This paper focuses on achieving RS-485 communication between programmable logical controller (PLC) and PC based on visual basic 6.0 (VB6.0) on an experimental automatic production line. Mitsubishi FX2N PLCs and a PC are chosen as slave stations and main station, respectively. Monitoring software is developed using VB6.0 for data input/output, flow control and online parameters setting. As a result, all functions are fulfilled with robust performance. It is concluded from results that one PC can monitor several PLCs using RS-485 communication.

  17. rsEGFP2 enables fast RESOLFT nanoscopy of living cells.

    PubMed

    Grotjohann, Tim; Testa, Ilaria; Reuss, Matthias; Brakemann, Tanja; Eggeling, Christian; Hell, Stefan W; Jakobs, Stefan

    2012-12-31

    The super-resolution microscopy called RESOLFT relying on fluorophore switching between longlived states, stands out by its coordinate-targeted sequential sample interrogation using low light levels. While RESOLFT has been shown to discern nanostructures in living cells, the reversibly photoswitchable green fluorescent protein (rsEGFP) employed in these experiments was switched rather slowly and recording lasted tens of minutes. We now report on the generation of rsEGFP2 providing faster switching and the use of this protein to demonstrate 25-250 times faster recordings.DOI:http://dx.doi.org/10.7554/eLife.00248.001.

  18. Association of GABRA6 1519 T>C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy.

    PubMed

    Prasad, D K V; Shaheen, Uzma; Satyanarayana, U; Prabha, T Surya; Jyothy, A; Munshi, Anjana

    2014-10-01

    The idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G gene polymorphisms with IGE. Molecular analysis revealed that the frequency of 'CC' genotype and 'C'allele of GABRA6 (rs3219151) T>C gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2=26; p<0.001; Odds ratio=3.6 (95% CI; 2.1-5.9); C vs T, χ2=24.7; p<0.001; Odds ratio=1.78 (95% CI; 1.4-2.2)]. The frequency of 'GG' genotype and 'G' allele of the intronic polymorphism A>G in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2=64.52; p<0.001; Odds ratio=7.37 (95% CI; 4.4-12.3); G vs. A, χ2=65.78; p<0.001; Odds ratio=2.57 (95% CI; 2.0-3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. The gene-gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2=36.6, p<0.001, Odds ratio=3.17 (95% CI; 2.2-4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene-gene interaction studies demonstrated significant interactive effects

  19. Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs.

    PubMed

    Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R; McIntosh, J Michael; Brunzell, Darlene H; Cannon, Jason R; Drenan, Ryan M

    2014-04-01

    α6β2* nicotinic acetylcholine receptors (nAChRs)s in the ventral tegmental area to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9'S mice) that are hypersensitive to nicotine and endogenous acetylcholine. Evoked extracellular dopamine (DA) levels were enhanced in α6L9'S NAc slices compared to control, non-transgenic (non-Tg) slices. Extracellular DA levels in both non-Tg and α6L9'S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by acetylcholine plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9'S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9'S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid compared to non-Tg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid, and norepinephrine (NE) were unchanged in α6L9'S compared to non-Tg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9'S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels.

  20. Genetic association of rs1344706 in ZNF804A with bipolar disorder and schizophrenia susceptibility in Chinese populations

    PubMed Central

    Rao, Shuquan; Yao, Yao; Ryan, Joanne; Jin, Chunhui; Xu, Yong; Huang, Xinhe; Guo, Jianxiu; Wen, Yueqiang; Mao, Canquan; Meyre, David; Zhang, Fuquan

    2017-01-01

    Rs1344706 in the the zinc finger protein 804A (ZNF804A) gene has been identified to be associated with schizophrenia and bipolar disorder (BD) in Europeans. However, whether rs1344706 is associated with schizophrenia in Chinese populations remains inconclusive; furthermore, the association between rs1344706 and BD in Chinese populations has been rarely explored. To explore the association between rs1344706 and schizophrenia/BD in Chinese populations, we genotyped rs1344706 among 1128 Chinese subjects (537 patients with BD and 591 controls) and found that rs1344706 showed marginal allelic association with BD (P = 0.028) with T-allele being more prevalent in cases than that in controls (OR = 1.19, 95% CI 1.03–1.37). Meta-analysis of rs1344706 by pooling all available data showed that rs1344706 was significantly associated with BD (P = 0.001). Besides, positive association of rs1344706 with schizophrenia was observed in Northern Chinese (P = 0.005). Furthermore, ZNF804A is highly expressed in human and mouse brains, especially in prenatal stage. PMID:28120939

  1. PCSK1 rs6232 Is Associated with Childhood and Adult Class III Obesity in the Mexican Population

    PubMed Central

    Villalobos-Comparán, Marisela; Villamil-Ramírez, Hugo; Villarreal-Molina, Teresa; Larrieta-Carrasco, Elena; León-Mimila, Paola; Romero-Hidalgo, Sandra; Jacobo-Albavera, Leonor; Liceaga-Fuentes, Adriana E.; Campos-Pérez, Francisco J.; López-Contreras, Blanca E.; Tusié-Luna, Teresa; del Río-Navarro, Blanca E.; Aguilar-Salinas, Carlos A.; Canizales-Quinteros, Samuel

    2012-01-01

    Background Common variants rs6232 and rs6235 in the PCSK1 gene have been associated with obesity in European populations. We aimed to evaluate the contribution of these variants to obesity and related traits in Mexican children and adults. Methodology/Principal Findings Rs6232 and rs6235 were genotyped in 2382 individuals, 1206 children and 1176 adults. Minor allele frequencies were 0.78% for rs6232 and 19.99% for rs6235. Rs6232 was significantly associated with childhood obesity and adult class III obesity (OR = 3.01 95%CI 1.64–5.53; P = 4×10−4 in the combined analysis). In addition, this SNP was significantly associated with lower fasting glucose levels (P = 0.01) and with increased insulin levels and HOMA-B (P = 0.05 and 0.01, respectively) only in non-obese children. In contrast, rs6235 showed no significant association with obesity or with glucose homeostasis parameters in any group. Conclusion/Significance Although rs6232 is rare in the Mexican population, it should be considered as an important risk factor for extreme forms of obesity. PMID:22737226

  2. Expression and polymorphism (rs4880) of mitochondrial superoxide dismutase (SOD2) and asparaginase induced hepatotoxicity in adult patients with acute lymphoblastic leukemia

    PubMed Central

    Alachkar, Houda; Fulton, Noreen; Sanford, Ben; Malnassy, Greg; Mutonga, Martin; Larson, Richard A.; Bloomfield, Clara D.; Marcucci, Guido; Nakamura, Yusuke; Stock, Wendy

    2016-01-01

    Asparaginase, which depletes asparagine and glutamine, activates amino acid stress response. Oxidative stress mediated by excessive reactive oxygen species (ROS) causes enhanced mitochondrial permeabilization and subsequent cell apoptosis and is considered a plausible mechanism for drug-induced hepatotoxicity, a common toxicity of asparaginase in adults with acute lymphoblastic leukemia (ALL). Studies investigating the pharmacogenetics of asparaginase in ALL are limited and focused on asparaginase-induced allergic reaction common in pediatric patients. Here, we sought to determine a potential association between the variant rs4880 in SOD2 gene, a key mitochondrial enzyme that protects cells against ROS, and hepatotoxicity during asparaginase-based therapy in 224 patients enrolled on CALGB-10102, a treatment trial for adults with ALL. We report that the CC genotype of rs4880 is associated with increased hepatotoxicity following asparaginase-based treatment. Thus, rs4880 likely contributes to asparaginase-induced hepatotoxicity, and functional studies investigating this SNP are needed to develop therapeutic approaches that mitigate this toxicity. PMID:27019981

  3. The rs10757278 polymorphism of the 9p21.3 locus is associated with premature coronary artery disease in Polish patients.

    PubMed

    Niemiec, Pawel; Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-09-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25-55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19-3.66) as well as the G allele (OR=1.49, 95% CI: 1.08-2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population.

  4. The rs10757278 Polymorphism of the 9p21.3 Locus Is Associated with Premature Coronary Artery Disease in Polish Patients

    PubMed Central

    Gorczynska-Kosiorz, Sylwia; Iwanicki, Tomasz; Krauze, Jolanta; Trautsolt, Wanda; Grzeszczak, Wladyslaw; Bochenek, Andrzej; Zak, Iwona

    2012-01-01

    Recently, genome-wide association studies have revealed a locus associated with coronary artery disease (CAD) and myocardial infarction, namely, 9p21.3. Its participation in the conditioning of the disease has been proven in many populations of European descent, but not yet in Slavs. Allelic variants of the rs10757278 polymorphism functionally affect the activity of the 9p21.3 locus; therefore, we conducted a study to determine whether the rs10757278 is associated with premature CAD in Polish patients. We studied 320 subjects aged 25–55 years, divided into two groups matched by sex and age: (1) patients with angiographically proven premature CAD (n=160), and (2) blood donors as a control group (n=160). The rs10757278 was genotyped using the method of fluorescently labeled allele-specific oligonucleotides. The frequency of the G allele was significantly higher in patients than in controls (58.2% vs. 42.8%, respectively, p=0.011) and was similar to the frequency of the GG homozygotes (30.6% vs. 17.5%, respectively, p=0.006). Both the GG homozygosity (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.19–3.66) as well as the G allele (OR=1.49, 95% CI: 1.08–2.07) have been associated with CAD in the analyzed population. These variants may be considered as risk factors, also in the Polish population. PMID:22946666

  5. Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome

    PubMed Central

    Xu-yang, Zheng; Pei-yu, Bian; Chuan-tao, Ye; Wei, Ye; Hong-wei, Ma; Kang, Tang; Chun-mei, Zhang; Ying-feng, Lei; Xin, Wei; Ping-zhong, Wang; Chang-xing, Huang; Xue-fan, Bai; Ying, Zhang; Zhan-sheng, Jia

    2017-01-01

    Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS. PMID:28096800

  6. A polymorphic indel containing the RS3 microsatellite in the 5' flanking region of the vasopressin V1a receptor gene is associated with chimpanzee (Pan troglodytes) personality.

    PubMed

    Hopkins, W D; Donaldson, Z R; Young, L J

    2012-07-01

    Vasopressin is a neuropeptide that has been strongly implicated in the development and evolution of complex social relations and cognition in mammals. Recent studies in voles have shown that polymorphic variation in the promoter region of the arginine vasopressin V1a receptor gene (avpr1a) is associated with different dimensions of sociality. In humans, variation in a repetitive sequence element in the 5' flanking region of the AVPR1A, known as RS3, have also been associated with variation in AVPR1a gene expression, brain activity and social behavior. Here, we examined the association of polymorphic variation in this same 5' flanking region of the AVPR1A on subjective ratings of personality in a sample of 83 chimpanzees (Pan troglodytes). Initial analyses indicated that 34 females and 19 males were homozygous for the short allele, which lacks RS3 (DupB(-/-)), while 18 females and 12 males were heterozygous and thus had one copy of the long allele containing RS3 (DupB(+/-)), yielding overall allelic frequencies of 0.82 for the DupB(-) allele and 0.18 for the DupB(+) allele. DupB(+/+) chimpanzees were excluded from the analysis because of the limited number of individuals. Results indicated no significant sex difference in personality between chimpanzees homozygous for the deletion of the RS3-containing DupB region (DupB(-/-)); however, among chimpanzees carrying one allele with the DupB present (DupB(+/-)), males had significantly higher dominance and lower conscientiousness scores than females. These findings are the first evidence showing that the AVPR1A gene plays a role in different aspects of personality in male and female chimpanzees.

  7. Contributions of β2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice

    PubMed Central

    Cole, Robert D.; Poole, Rachel L.; Guzman, Dawn M.; Gould, Thomas J.; Parikh, Vinay

    2014-01-01

    Rationale Deficits in executive functions underlie compulsive drug use and understanding how nicotine influences these cognitive processes may provide important information on neurobiological substrates of nicotine addiction. Accumulating evidence suggests that β2 subunit-containing nicotinic receptors (nAChRs) are involved in the reinforcing process of nicotine addiction. Whether these nAChRs also contributes to the detrimental effects of chronic nicotine on flexible decision-making is not known. Objectives In the present study, the effects of chronic nicotine were assessed in mice with partial or complete deletion of the β2-subunit containing nAChR gene (β2+/- or β2-/-) performing an operant cognitive flexibility task. Results Visual discrimination learning was not affected in saline-treated β2 nAChR mutants as compared to the wild-type (β2+/+) mice; yet, chronic nicotine facilitated acquisition of visual discrimination in all genotypes. The acquisition of new egocentric response strategy set-shifting remained similar in all genotypes and there was no effect of treatment. Chronic nicotine treatment impaired reversal learning in β2+/+ mice by increasing response perseveration to the previously rewarded stimulus. Moreover, the acquisition of inverted stimulus-reward contingencies did not differ between β2+/+ and β2-/- mice exposed to chronic nicotine. Interestingly, nicotine-induced reversal learning deficits were not observed in β2+/- mice. Conclusions Collectively, these findings suggest that β2 subunit-containing nAChRs are not critical for visual discrimination learning and extradimensional rule shift. However, sustained activation of these nAChRs with nicotine may interfere with inhibitory control processes influencing affective shifts in stimulus-reward contingencies. PMID:25281224

  8. MERISTEM-DEFECTIVE, an RS domain protein, is required for the correct meristem patterning and function in Arabidopsis.

    PubMed

    Casson, Stuart A; Topping, Jennifer F; Lindsey, Keith

    2009-03-01

    Plant growth and development is dependent on the specification and maintenance of pools of stem cells found in the meristems. Mutations in the Arabidopsis MERISTEM-DEFECTIVE (MDF) gene lead to a loss of stem cell and meristematic activity in the root and vegetative shoot. MDF encodes a putative RS domain protein with a predicted role in transcription or RNA processing control. mdf mutants exhibit decreased levels of PINFORMED2 (PIN2) and PIN4 mRNAs, which is associated with a reduction in PIN:GFP levels, and with a defective auxin maximum in the basal region of the developing mdf embryo and seedling root meristem. Seedling roots also exhibit reduced PLETHORA (PLT), SCARECROW and SHORTROOT gene expression, a loss of stem cell activity, terminal differentiation of the root meristem and defective cell patterning. MDF expression is not defective in the bodenlos, pin1 or eir1/pin2 auxin mutants, and is not modulated by exogenous auxin. plt1 plt2 double mutants have unaffected levels of MDF RNA, indicating that MDF acts upstream of PIN and PLT gene expression. Differentiation of the shoot stem cell pool also occurs in mdf mutants, associated with a reduced WUSCHEL (WUS) expression domain and expanded CLAVATA3 (CLV3) domain. Overexpression of MDF leads to the activation of markers of embryonic identity and ectopic meristem activity in vegetative tissues. These results demonstrate a requirement for the MDF-dependent pathway in regulating PIN/PLT- and WUS/CLV-mediated meristem activity.

  9. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells

    PubMed Central

    Starost, Laura Julia; Karassek, Sascha; Sano, Yasuteru; Kanda, Takashi; Kim, Kwang Sik; Dobrindt, Ulrich; Rüter, Christian; Schmidt, Marcus Alexander

    2016-01-01

    Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB. PMID:27754355

  10. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells.

    PubMed

    Starost, Laura Julia; Karassek, Sascha; Sano, Yasuteru; Kanda, Takashi; Kim, Kwang Sik; Dobrindt, Ulrich; Rüter, Christian; Schmidt, Marcus Alexander

    2016-10-13

    Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood-brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218's effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB.

  11. Surviving as a Postmodern Social Worker: Two Ps and Three Rs of Direct Practice

    ERIC Educational Resources Information Center

    Ungar, Michael

    2004-01-01

    Social workers interested in postmodernism have been pr